Pharmacogenetics of KCNQ channel activation in 2 potassium channelopathy mouse models of epilepsy

Summary

Objectives

Antiseizure drugs are the leading therapeutic choice for treatment of epilepsy, but their efficacy is limited by pharmacoresistance and the occurrence of unwanted side effects. Here, we examined the therapeutic efficacy of KCNQ channel activation by retigabine in preventing seizures and neurocardiac dysfunction in 2 potassium channelopathy mouse models of epilepsy with differing severity that have been associated with increased risk of sudden unexpected death in epilepsy (SUDEP): the Kcna1^−/− model of severe epilepsy and the Kcnq1^A340E/A340E model of mild epilepsy.

Methods

A combination of behavioral, seizure threshold, electrophysiologic, and gene expression analyses was used to determine the effects of KCNQ activation in mice.

Results

Behaviorally, Kcna1^−/− mice exhibited unexpected hyperexcitability instead of the expected sedative-like response. In flurothyl-induced seizure tests, KCNQ activation decreased seizure latency by ≥50% in Kcnq1 strain mice but had no effect in the Kcna1 strain, suggesting the influence of genetic background. However, in simultaneous electroencephalography and electrocardiography recordings, KCNQ activation significantly reduced spontaneous seizure frequency in Kcna1^−/− mice by ~60%. In Kcnq1^A340E/A340E mice, KCNQ activation produced adverse cardiac effects including profound bradycardia and abnormal increases in heart rate variability and atrioventricular conduction blocks. Analyses of Kcnq2 and Kcnq3 mRNA levels revealed significantly elevated Kcnq2 expression in Kcna1^−/− brains, suggesting that drug target alterations may contribute to the altered drug responses.

Significance

This study shows that treatment strategies in channelopathy may have unexpected outcomes and that effective rebalancing of channel defects requires improved understanding of channel interactions at the circuit and tissue levels. The efficacy of KCNQ channel activation and manifestation of adverse effects were greatly affected by genetic background, potentially limiting KCNQ modulation as a way to prevent neurocardiac dysfunction in epilepsy and thereby SUDEP risk. Our data also uncover a potential role for KCNQ2-5 channels in autonomic control of chronotropy.

http://ift.tt/2D2y9bg

Issue Cover (December 2017)

Cover image by Dr. Natalie Doig (MRC Brain Network Dynamics Unit, Department of Pharmacology, Oxford). The cover image is of a frontal section of mouse brain showing many regions of the basal ganglia. The section was triple-immunostained to reveal tyrosine hydroxylase (TH; cyan), parvalbumin (PV; green) and choline acetyltransferase (magenta).

http://ift.tt/2yUHz5v

Immunogenicity of Recombinant Adenovirus Type 5 Vector-Based Ebola Vaccine Expressing Glycoprotein from the 2014 Epidemic Strain in Mice

Human Gene Therapy , Vol. 0, No. 0.


http://ift.tt/2khyIpM

Qualitative methods in Asian American psychology.

The lives of Asian Americans living in the United States are both diverse and rich. To best capture the breadth of their experiences, a range of methodological approaches is needed. Although quantitative methods are most frequently represented in psychological studies focused on Asian Americans, qualitative methods have also significantly contributed to the field and gained increasing attention over time. This article introduces Part 1 of a 2-part special issue devoted to studies that use qualitative methods to examine a range of Asian American topics. Part 1 of the issue begins with a 12-year content review of qualitative research on Asian American psychological well-being to provide a broad overview of past qualitative methods and topics. Following this, individual studies are presented that investigate specific experiences regarding body image among heterosexual Asian American women, parental racial socialization among transracially adopted Korean American adults raised by White parents, adolescent views on the indigenous Chinese parent–child relationship concept of qin in immigrant Chinese families, and the impacts of a coordinating council in facilitating community health programs that serve Chinese American families. The studies incorporate a variety of methods and highlight the contributions of qualitative inquiry in understanding the lives of Asian Americans. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2oFpZSX

“I’m learning not to tell you”: Korean transracial adoptees’ appraisals of parental racial socialization strategies and perceived effects.

Although studies generally find that transracially adopted children who are socialized in their birth or ethnic culture report higher levels of psychological well-being, studies of racial socialization report conflicting results (Boivin & Hassan, 2015). These inconsistencies highlight the complexity and distinctiveness of racial socialization processes and the need to better understand how parental messages about racial diversity and racism are experienced across developmental periods. Drawing on constructivist and poststructuralist paradigms, 8 focus groups explored the racial socialization narratives of 34 Korean American transracially adopted adults raised by White parents. The aims were to explore subjective experiences of parental racial socialization strategies and their perceived effect on identity development and other key areas of functioning. Analysis of focus group transcripts was informed by grounded theory and narrative frameworks. Parent socialization strategies were classified as avoidant (color-blind or passive/child-choice), ambivalent, or engaged (active/child-focused or participatory/multicultural family). Avoidant and ambivalent approaches were most common and reinforced by participants' own desire for racial sameness in childhood. As participants traversed middle childhood and adolescence, they increasingly viewed avoidant and ambivalent parents as vulnerable, biased, and ill equipped to handle the racial realities of their lives. The perceived fragility of these parents led participants to suppress stories of racial marginalization and oppression, created distance in the relationship, impeded the process of identity exploration, and left them unprepared to cope with racist events. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2CYFqbU

Parent–adolescent relationships among Chinese immigrant families: An indigenous concept of qin.

This study investigated cultural meanings of positive Chinese parent–child relationships through exploration of an indigenous concept, qin, as experienced by Chinese American adolescents of immigrant parents. Semistructured interviews were conducted with 15 first-generation and second-generation Chinese American high school students of immigrant parents, focusing on adolescents' descriptions of the meaning of qin and parental behaviors that foster this quality. According to the Chinese American adolescents who were interviewed, being qin with parents was characterized as closeness to parents and a general sense of togetherness and harmony; showing parents their love through respect, obedience, academic effort, and appreciation; and open communication with the parents, particularly about school. This relationship is primarily fostered by parental devotion and sacrifice, particularly for the child's education, future opportunities, success, and needs. The results highlight the role of child reciprocation of love and devotion for the parents in a qin relationship. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2oD0Wjo

Content review of qualitative research on Asian American psychological well-being.

Qualitative methods have made important contributions to Asian American psychology. To date, annual reviews of research in the Asian American Journal of Psychology have not focused on the nature and status of qualitative studies in the field. To address this gap, the present study provides a content review of 12 years of qualitative research related to Asian American psychological well-being, published between 2003 and 2014. Using PsycINFO, 487 relevant articles were identified and coded for publication journal, study sample and qualitative research method characteristics, and topical focus. The most frequently studied populations in the 12-year span were Korean and Chinese, immigrants, community adults, heterogeneous samples including women and men, and individuals living in the western and northeastern regions of the United States. Grounded theory emerged as the predominant qualitative method approach, and individual interviews were the most prevalent form of data collection. Nearly half of the reviewed studies lacked identification of a specific qualitative approach, and a similar percentage lacked a description of trustworthiness/credibility checks. The most frequently studied topic was mental health, followed by physical health. Additional topics covered in this review include self and identity, family dynamics, acculturation, interpersonal violence, aging, education, racism, religion, and work. Descriptive summaries of studies within topic areas are provided as well as a discussion of broader themes, methodological patterns, and future recommendations. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2D0QK7u

Strategic collaborative partnerships to improve immigrant Chinese community health: A case study.

The present study used a qualitative case study method, supplemented with a brief survey measure, to explore how university-based, coordinated strategic partnerships contributed to the process of culturally adapting and implementing evidence-based health programs. These programs aimed to improve the well-being of low-income immigrant families traditionally underserved by health interventions. Our case study examined a university-initiated coordinating council that oversaw 3 separate evidence-based health prevention interventions designed to reduce childhood obesity, reduce exposure to secondhand smoke, and promote health and behavioral outcomes among low-income immigrant Chinese families. Each project used community-based participatory research (Israel, Schulz, Parker, & Becker, 1998) approach to culturally adapt and implement the interventions. We used content analysis to examine archival data (e.g., council meeting notes and transcripts and project progress reports) and interviews with 4 council members, supplemented with a brief survey of council effectiveness rated by the council members (N = 19). We found that having a centrally coordinated council to oversee multiple community-based participatory research health programs appeared to add unique values to the success of each individual program, specifically by promoting a sense of shared learning around cultural adaptation specific to urban, low-income Chinese American families, and by identifying and collaborating to improve social determinants of community health. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2oIpQhC

Exploring the conceptualization of body image for Asian American women.

The present study explored racial and cultural factors that influence body image development with a sample of 10 heterosexual Asian American women through in-person, semistructured interviews. Data were analyzed via the consensual qualitative research methodology (Hill, 2012; Hill et al., 2005) and highlighted several factors shaping body image for Asian American women: (a) interpersonal influences, (b) Asian and American body ideals, (c) thin-ideal internalization, and (d) protective behaviors and attitudes. The findings specifically identify the most frequently reported categories as male gazing, nonfamilial close relationships, and standards of body/beauty established by both Asian and American cultures. Limitations of findings and future research directions are provided. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

http://ift.tt/2CYHpNs

Key High Efficiency Practices of Emergency Department Providers: A Mixed Methods Study

Abstract

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed methods study design was utilized to identify key behaviors associated with efficiency:

Stage 1. A convenience sample of sixteen participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semi-structured interviews. Ninety-nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes.

Stage 2. An observational study of 35 providers was performed in four (30,000 to 55,000-visit) community EDs during two 4-hour periods and recorded in minute-by-minute observation logs.

Stage 3. Each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (Relative Value Units [RVUs] per hour) using linear univariate generalized estimating equations (GEE) with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, "inefficiency practices", demonstrated significant negative correlations: non-work-related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members is associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

This article is protected by copyright. All rights reserved.

http://ift.tt/2yV8NsD

Clinical examination for acute aortic dissection: A systematic review and meta-analysis

Abstract

Introduction

Acute aortic dissection is a life-threatening condition due to a tear in the aortic wall. It is difficult to diagnose and if missed carries a significant mortality.

Methods

We conducted a librarian assisted systematic review of Pubmed, Medline, Embase and the Cochrane database from 1968 to July 2016. Titles and abstracts were reviewed and data extracted by two independent reviewers (agreement measured by Kappa). Studies were combined if low clinical and statistical heterogeonity (I²<30%). Study quality was assessed using the QUADAS-2 tool. Bivariate random effects meta analyses using Revman 5 and SAS 9.3 were performed.

Results

We identified 792 records: 60 were selected for full text review, 9 studies with 2,400 participants were included (QUADAS-2 low risk of bias, Kappa 0.89(for full text review)). Prevalence of aortic dissection ranged from 21.9-76.1% (mean 39.1% SD 17.1%). The clinical findings increasing probability of aortic dissection were: 1) neurological deficit (n=3, specificity 95%, LR+ 4.4 95% CI 3.3-5.7, I² 0%), 2) hypotension (n=4, specificity 95%, LR+ 2.9 95% CI 1.8-4.6, I² 42%), and decreasing probability: absence of a widened mediastinum (n=4, sensitivity 76%-95%, LR- 0.14-0.60, I² 93%) and an American heart association (AHA) aortic dissection detection (ADD) risk score <1 (n=1 sensitivity 91%, LR- 0.22 95% CI 0.15–0.33).

Conclusions

Suspicion for acute aortic dissection should be raised with hypotension, pulse or neurological deficit. Conversely, a low AHA ADD score decreases suspicion. Clinical gestalt informed by high and low risk features together with an absence of an alternative diagnosis should drive investigation for acute aortic dissection.

This article is protected by copyright. All rights reserved.

http://ift.tt/2BbSvBy

Post-surgical effects on language in patients with presumed low-grade glioma

Objectives

Low-grade glioma (LGG) is a slow-growing brain tumour often situated in or near areas involved in language and/or cognitive functions. Thus, language impairments due to tumour growth or surgical resection are obvious risks. We aimed to investigate language outcome following surgery in patients with presumed LGG, using a comprehensive and sensitive language assessment.

Materials and methods

Thirty-two consecutive patients with presumed LGG were assessed preoperative, early post-operative, and 3 months post-operative using sensitive tests including lexical retrieval, language comprehension and high-level language. The patients' preoperative language ability was compared with a reference group, but also with performance at post-operative controls. Further, the association between tumour location and language performance pre- and post-operatively was explored.

Results

Before surgery, the patients with presumed LGG performed worse on tests of lexical retrieval when compared to a reference group (BNT: LGG-group median 52, Reference-group median 54, P = .002; Animals: LGG-group mean 21.0, Reference-group mean 25, P = 001; Verbs: LGG-group mean 17.3, Reference-group mean 21.4, P = .001). At early post-operative assessment, we observed a decline in all language tests, whereas at 3 months there was only a decline on a single test of lexical retrieval (Animals: preoperative. median 20, post-op median 14, P = .001).

The highest proportion of language impairment was found in the group with a tumour in language-eloquent areas at all time-points.

Conclusions

Although many patients with a tumour in the left hemisphere deteriorated in their language function directly after surgery, their prognosis for recovery was good.

http://ift.tt/2kIMiSt

Is carotid imaging underused in patients with transient ischemic attack or ischemic stroke? A Swedish Stroke Register (Riksstroke) study

Background and aim

Carotid artery stenosis is one of the major causes of transient ischemic attack (TIA) and acute ischemic stroke (IS), and carotid surgery and stenting are used to reduce the risk of ipsilateral IS. However, the adherence to the recommendation of carotid imaging in clinical practice has not been well studied. We analyzed proportions of carotid imaging and determinants for its non-use in patients with TIA and IS with respect to baseline demographics, risk factors, hospital characteristics, and geographical region.

Patients and methods

Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). Carotid imaging diagnostics included carotid Doppler ultrasound and computed tomography angiography.

Results

Carotid imaging was performed in 70% (10 545/15 021) of patients with TIA and 54% (23 772/44 075) of patients with IS. The most significant independent determinants for not undergoing carotid imaging were, in patients with TIA: age ≥85 year (odds ratio (OR), 7.3; 95% confidence interval (CI), 6.4-8.4) and a history of stroke (OR, 2.3; 95% CI, 2.1-2.5); and in patients with IS: age ≥85 year (OR, 9.8; 95% CI, 9.0-10.6), age 75-84 year (OR, 2.5; 95% CI, 2.3-2.7), and reduced level of consciousness at admission (OR, 3.4; 95% CI, 3.1-3.6). Care at a University hospital and in a stroke unit increased the likelihood of carotid imaging. There were substantial regional variations regarding proportions of carotid imaging.

Conclusion

Carotid imaging appears to be underused in patients with TIA and IS. Opportunities of secondary stroke prevention with carotid interventions are likely missed.

http://ift.tt/2kh0seg

Man With Bulging Blisters

A 54-year-old Hispanic man presented with a generalized pruritic and blistering rash for 8 days, involving his face, oral cavity, neck, torso, back, upper extremities, and groin (Figures 1 and 2). He denied fever, and vital signs were within normal limits. Physical examination was notable for diffuse and symmetric, variably sized, tense bullae over the affected areas and intertriginous folds, with negative Nikolsky's sign (Figure 3). Oral mucosa was moist, with tender erosive ulcers involving the hard palate and gingiva (Figure 4).

http://ift.tt/2kJf9pG

Greater Love Than That

This father was in his early thirties and solidly built. He was a man who had other concerns than his physical appearance that morning. His white undershirt, now gray and threadbare, with a small lenticular rip at the neck, was wrinkled at the bottom where it was tucked in yesterday. On his unshaven face, he wore sensible wire-rimmed glasses that slipped down his nose. Trying to adjust them with his middle finger proved to be an awkward movement, considering that both arms were already full of his 4-year-old son.

http://ift.tt/2D0IIve

The End

"35-year-old male in bed 4 CC: Respiratory distress, EtOH, jaundice. Triage level 2." Charts like that can hide dark histories.

http://ift.tt/2D2ekRh

Young Man With Left Arm Pain and Swelling

A 19-year-old previously healthy man presented to the emergency department (ED) with 1-day history of progressive left arm pain and swelling. The day before, the patient had been performing overhead shoulder presses, using 30-lb dumbbells. He reported an immediate twinge of pain in the left arm during the exercise. The pain subsided with rest, but mild edema to the left arm ensued. The following morning, the patient noted increasing pain and swelling to the left arm, with marked ecchymotic discoloration (Figures 1 and 2).

http://ift.tt/2kKB3c7

Elderly Woman With Vomiting

An 85-year-old woman with Alzheimer's disease presented to our emergency department after 2 days of intermittent vomiting. Her initial vital signs showed blood pressure 80/60 mm Hg, pulse rate 170 beats/min, and tympanic temperature of 36.8°C (98.2°F). Physical examination revealed abdominal distention, hypoactive bowel sounds, and right lower quadrant tenderness. Contrast-enhanced computed tomography (CT) showed gallstone ileus with Rigler's triad,1 including an ectopic stone, mechanical bowel obstruction, and pneumobilia (Figures 1 and 2).

http://ift.tt/2D2eAjd

Elderly Male With Shortness of Breath

An 87-year-old man presented to the emergency department with shortness of breath without chest pain, palpitations, or diaphoresis. He had a history of atrial fibrillation with a previous left atrial thrombus. On examination, he was afebrile, with an irregular pulse rate of 86 beats/min and a blood pressure of 103/66 mm Hg. The jugular venous pressure was elevated and the jugular vein was noteworthy for giant systolic pulsations with prominent v waves (Figure and Video E1 [available online at http://ift.tt/P50aok]).

http://ift.tt/2kJ07k0

Young Child in Respiratory Distress

A 2-year-old girl presented with acute respiratory distress. On admission, she was alert but with severe dyspnea. Her temperature was 38.2°C (100.7°F), respiratory rate 64 breaths/min, and oxygen saturation 87% on room air. Pulmonary examination revealed bilateral decreased breath sounds and expiratory wheezing. Despite aggressive therapy with nebulized and intravenous albuterol and systemic steroids, dyspnea and decreased breath sounds in the right lung field persisted. A chest radiograph was obtained (Figure 1).

http://ift.tt/2kJV96B

Chest Pain in a Patient With a Left Bundle Branch Block

A 76-year-old woman presented to the emergency department with acute chest pain for 20 minutes. The chest pain radiated to the neck, jaw, and teeth, and was associated with nausea, dyspnea, and diaphoresis. The patient was hemodynamically stable and appeared only slightly uncomfortable. The cardiac and pulmonary examination results were normal, and the remainder of the examination was unremarkable. The ECG on arrival is shown in Figure 1. No previous ECGs were available.

http://ift.tt/2D2elVl

It May Come as No Shock: Cardioversion of Atrial Fibrillation and Atrial Flutter With Ibutilide

http://ift.tt/2kGth38

Assessment of Hospital Emergency Department Response to Potentially Infectious Diseases Using Unannounced Mystery Patient Drills—New York City, 2016

[Foote MMK, Styles TS, Quinn CL. Assessment of hospital emergency department response to potentially infectious diseases using unannounced mystery patient drills—New York City, 2016. MMWR Morb Mortal Wkly Rep. 2017;66:945-949.]

http://ift.tt/2CXkceC

What to Do After You Cut: Recommendations for Abscess Management in the Emergency Setting

SEE RELATED ARTICLE, P. 21.

http://ift.tt/2CYrnTI

The Digital Doctor: Hope, Hype, and Harm at the Dawn of Medicine’s Computer Age

Medicine is the most information-rich, knowledge-intensive human activity, probably ever.—Matthew Burton, The Digital Doctor

http://ift.tt/2kI8Bb2

Global Research Highlights

Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at http://ift.tt/2dmKsCb.

http://ift.tt/2CZ9RyP

Lessons From an Extreme Hurricane Season

During the height of Hurricane Harvey, when Houston was awash with water, there was roughly an 18-hour stretch when the emergency department (ED) staff at Memorial Hermann Red Duke Trauma Institute had virtually no incoming patients, said James McCarthy, MD, chief of emergency medicine.

http://ift.tt/2CYr638

When Race Becomes an Issue in Emergency Department Treatment

In the days after the August 2017 racial clashes in Charlottesville, VA, a faked photo of an injured Klansman being treated by an all-black emergency department (ED) staff went viral on social media.

http://ift.tt/2CYqTgm

Commentary

Increasing globalization and travel has allowed infections to spread more easily and has resulted in the potential for more frequent outbreaks. Outbreaks of severe acute respiratory syndrome (2003), MERS (2012 to 2014), measles (2014), and Ebola virus disease (2014) highlight the importance of rapidly identifying, isolating, and appropriately managing the care of patients with highly communicable diseases of public health concern to prevent nosocomial spread of illness to other patients, staff, and visitors.

http://ift.tt/2kJeDIg

Correction

Erratum to 'Two Days of Dexamethasone Versus 5 Days of Prednisone in the Treatment of Acute Asthma: A Randomized Controlled Trial'

http://ift.tt/2CZ9S5R

Modeling pathogenesis and treatment response in childhood absence epilepsy

Summary

Objective

Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE.

Methods

The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABA_A, and GABA_B synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABA_A conductance.

Results

Decreasing cortical GABA_A conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type.

Significance

These results provide a window into mechanisms underlying polygenic inheritance in CAE, as well as a mechanism for treatment effects and failures mediated by these channels. Although the model is a simplification of the human thalamocortical network, it serves as a useful starting point for predicting the implications of ion channel electrophysiology in polygenic epilepsy such as CAE.

http://ift.tt/2CW6JDL

Genomic Prediction and Association Mapping of Curd-Related Traits in Genebank Accessions of Cauliflower

Genetic resources are an important source of genetic variation for plant breeding. Genome-wide association studies (GWAS) and genomic prediction greatly facilitate the analysis and utilization of useful genetic diversity for improving complex phenotypic traits in crop plants. We explored the potential of GWAS and genomic prediction for improving curd-related traits in cauliflower (Brassica oleracea var. botrytis) by combining 174 randomly selected cauliflower genebank accessions from two different genebanks. The collection was genotyped with genotyping-by-sequencing (GBS) and phenotyped for six curd-related traits at two locations and three growing seasons. A GWAS analysis based on 120,693 SNPs identified a total of 24 significant associations for curd-related traits. The potential for genomic prediction was assessed with a genomic best linear unbiased prediction model (GBLUP) and BayesB. Prediction abilities ranged from 0.10 to 0.66 for different traits and did not differ between prediction methods. Imputation of missing genotypes did only slightly improve prediction ability. Our results demonstrate that GWAS and genomic prediction in combination with GBS and phenotyping of highly heritable traits can be used to identify useful quantitative trait loci (QTL) and genotypes among genetically diverse genebank material for subsequent utilization as genetic resources in cauliflower breeding.

http://ift.tt/2AYYdmk

Selection Mapping Identifies Loci Underpinning Autumn Dormancy in Alfalfa (Medicago sativa)

Autumn dormancy in alfalfa (Medicago sativa) is associated with agronomically important traits including regrowth rate, maturity, and winter survival. Historical recurrent selection experiments have been able to manipulate the dormancy response. We hypothesized that artificial selection for dormancy phenotypes in these experiments had altered allele frequencies of dormancy-related genes. Here we follow this hypothesis and analyze allele frequency changes using genome-wide polymorphisms in the pre- and post-selection populations from one historical selection experiment. We screened the non-dormant cultivar CUF 101 and populations developed by three cycles of recurrent phenotypic selection for taller and shorter plants in autumn with markers derived from genotyping-by-sequencing (GBS). We validated the robustness of our GBS-derived allele frequency estimates using an empirical approach. Our results suggest that selection mapping is a powerful means of identifying genomic regions associated with traits and that it can be exploited to provide regions on which to focus further mapping and cloning projects.

http://ift.tt/2AWhvZm

Joint Analysis of Strain and Parent-of-Origin Effects for Recombinant Inbred Intercrosses Generated from Multiparent Populations with the Collaborative Cross as an Example

Multiparent populations (MPP) have become popular resources for complex trait mapping because of their wider allelic diversity, and larger population size compared to traditional two-way recombinant inbred (RI) strains. In Mice, the Collaborative Cross (CC) is one of the most popular MPP and is derived from eight genetically diverse inbred founder strains. The strategy of generating recombinant inbred intercrosses (RIX) from MPP in general and the CC in particular can produce a large number of completely reproducible heterozygote genomes that better represent the (outbred) human population. Since both maternal and paternal haplotypes of each RIX are readily available, RIX is a powerful resource for studying both standing genetic and epigenetic variations of complex traits, in particular, the Parent-of-Origin (PoO) effects, an important contributor to many complex traits. Furthermore, most complex traits are affected by more than one genes where multiple QTL mapping could be more advantageous. In this paper, for MPP-RIX data but taking CC-RIX as a working example, we propose a general Bayesian variable selection procedure to simultaneously search for multiple genes with founder allelic effects and PoO effects. The proposed model respects the complex relationship among RIX samples and the performance of the proposed method is examined by extensive simulations.

http://ift.tt/2BJSIeO

Pleiotropic Roles for ZEB1 in Cancer

ZEB1 is a prime element of a network of transcription factors that controls epithelial-to-mesenchymal transition (EMT), a reversible embryonic transdifferentiation program that allows partial or complete transition from an epithelial to a mesenchymal state. Aberrant expression of ZEB1 has been reported in a variety of human cancers, where it is generally believed to foster migration, invasion, and metastasis. Over the past few years, in vitro and in vivo observations have highlighted unsuspected intrinsic oncogenic functions of ZEB1 that impact tumorigenesis from its earliest stages. Located downstream of regulatory processes that integrate microenvironmental signals and directly implicated in feedback loops controlled by miRNAs, ZEB1 appears to be a central switch that determines cell fate. Its expression fosters malignant transformation through the mitigation of critical oncosuppressive pathways and through the conferment of stemness properties. ZEB1 is also a key determinant of cell plasticity, endowing cells with the capacity to withstand an aberrant mitogenic activity, with a profound impact on the genetic history of tumorigenesis, and to adapt to the multiple constraints encountered over the course of tumor development. Cancer Res; 78(1); 1–6. ©2017 AACR.

http://ift.tt/2AVAe7w

New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome

The human protein kinome comprises 535 proteins that, with the exception of approximately 50 pseudokinases, control intracellular signaling networks by catalyzing the phosphorylation of multiple protein substrates. While a major research focus of the last 30 years has been cancer-associated Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at least one disease or developmental disorder. Despite this remarkable statistic, for the majority of protein kinases and pseudokinases, there are currently no inhibitors progressing toward the clinic, and in most cases, details of their physiologic and pathologic mechanisms remain at least partially obscure. By curating and annotating data from the literature and major public databases of phosphorylation sites, kinases, and disease associations, we generate an unbiased resource that highlights areas of unmet need within the kinome. We discuss strategies and challenges associated with characterizing catalytic and noncatalytic outputs in cells, and describe successes and new frontiers that will support more comprehensive cancer-targeting and therapeutic evaluation in the future. Cancer Res; 78(1); 1–15. ©2017 AACR.

http://ift.tt/2BJJhvS

Novel Targeting of Transcription and Metabolism in Glioblastoma

Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become effective therapeutics for GBM patients. Experimental Design: To investigate TG02, an agent with known penetration of the Blood-Brain Barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We utilized human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02.  Mechanistic studies included TG02-induced transcriptional regulation, apoptosis and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays. Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of anti-apoptotic proteins, and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue. Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial.

http://ift.tt/2CBi2Af

Colonization with multidrug-resistant bacteria increases the risk of complications and a fatal outcome after allogeneic hematopoietic cell transplantation

Abstract

Composition of the gut microbiota seems to influence early complications of allogeneic hematopoietic cell transplantation (HCT) such as bacterial infections and acute graft-versus-host disease (GVHD). In this study, we assessed the impact of colonization with multidrug-resistant bacteria (MDRB) prior to HCT and the use of antibiotics against anaerobic bacteria on the outcomes of HCT. We retrospectively analyzed the data of 120 patients who underwent HCT for hematologic disorders between 2012 and 2014. Fifty-one (42.5%) patients were colonized with MDRB and 39 (32.5%) had infections caused by MDRB. Prior colonization was significantly correlated with MDRB infections (P < 0.001), especially bacteremia (P = 0.038). A higher incidence of MDRB infections was observed in patients with acute (P = 0.014) or chronic (P = 0.002) GVHD and in patients aged > 40 years (P = 0.002). Colonization had a negative impact on overall survival (OS) after HCT (64 vs. 47% at 24 months; P = 0.034) and infection-associated mortality (P < 0.001). Use of metronidazole was correlated with an increased incidence of acute GVHD (P < 0.001) and lower OS (P = 0.002). Patients colonized with MDRB are more susceptible to life-threatening infections. Colonization with virulent flora is the most probable source of neutropenic infection; therefore, information about prior positive colonization should be crucial for the selection of empiric antibiotic therapy. The use of metronidazole, affecting the biodiversity of the intestinal microbiome, seems to have a significant impact on OS and acute GVHD.

http://ift.tt/2yUpMeE

A Comparison of Fosaprepitant and Ondansetron for Preventing Postoperative Nausea and Vomiting in Moderate to High Risk Patients: A Retrospective Database Analysis

Postoperative nausea and vomiting (PONV) occur in 30–50% of patients undergoing general anesthesia and in 70–80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, ) and intravenous ondansetron 4 mg (ONS group, ) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0–2, 0–24, and 0–48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0–48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0–48 hours after surgery.

http://ift.tt/2yTDn61

The Improvement of Laparoscopic Surgical Skills Obtained by Gynecologists after Ten Years of Clinical Training Can Reduce Peritoneal Adhesion Formation during Laparoscopic Myomectomy: A Retrospective Cohort Study

Objective. To evaluate if improvement of laparoscopic skills can reduce postoperative peritoneal adhesion formation in a clinical setting. Study Design. We retrospectively evaluated 25 women who underwent laparoscopic myomectomy from January 1993 to June 1994 and 22 women who underwent laparoscopic myomectomy from March 2002 to November 2004. Women had one to four subserous/intramural myomas and received surgery without antiadhesive agents or barriers. Women underwent second-look laparoscopy for assessment of peritoneal adhesion formation 12 to 14 weeks after myomectomy. Adhesions were graded according to the Operative Laparoscopy Study Group scoring system. The main variable to be compared between the two cohorts was the proportion that showed no adhesions at second-look laparoscopy. Results. Demographic and surgical characteristics were similar between the two cohorts. No complications were observed during surgery. No adverse events were recorded during postoperative course. At second-look laparoscopy, a higher proportion of adhesion-free patients was observed in women who underwent laparoscopic myomectomy from March 2002 to November 2004 (9 out of 22) compared with women who underwent the same surgery from January 1993 to June 1994 (3 out of 25). Conclusion. The improvement of surgeons' skills obtained after ten years of surgery can reduce postoperative adhesion formation.

http://ift.tt/2yUO5sM

Death, injury and disability from kinetic impact projectiles in crowd-control settings: a systematic review

Objective

We conducted a systematic review of the available literature on deaths, injuries and permanent disability from rubber and plastic bullets, as well as from bean bag rounds, shot pellets and other projectiles used in arrests, protests and other contexts from 1 January 1990 until 1 June 2017.

Data sources

PubMed, Scopus, JSTOR and grey literature.

Data synthesis

We report on descriptive statistics as well as data on injury severity, permanent disability and death. We analysed potential risk factors for injury severity, including the site of impact, firing distance and access to medical care.

Results

Of 3228 identified articles, 26 articles met inclusion criteria. These articles included injury data on 1984 people, 53 of whom died as a result of their injuries. 300 people suffered permanent disability. Deaths and permanent disability often resulted from strikes to the head and neck (49.1% of deaths and 82.6% of permanent disabilities). Of the 2135 injuries in those who survived their injuries, 71% were severe, injuries to the skin and to the extremities were most frequent. Anatomical site of impact, firing distance and timely access to medical care were correlated with injury severity and risk of disability.

Conclusions

Kinetic impact projectiles (KIPs), often called rubber or plastic bullets, are used commonly in crowd-control settings. We find that these projectiles have caused significant morbidity and mortality during the past 27 years, much of it from penetrative injuries and head, neck and torso trauma. Given their inherent inaccuracy, potential for misuse and associated health consequences of severe injury, disability and death, KIPs do not appear to be appropriate weapons for use in crowd-control settings. There is an urgent need to establish international guidelines on the use of crowd-control weapons to prevent unnecessary injuries and deaths.

http://ift.tt/2oEyM7S

Least Injurious Mechanical Ventilation in Pulmonary Resection Surgery

No abstract available

http://ift.tt/2kh22wJ

To Clot or Not to Clot: Understanding Coagulopathy in Liver Disease

No abstract available

http://ift.tt/2ke55WA

Unadjusted Bivariate Two-Group Comparisons: When Simpler is Better

Hypothesis testing involves posing both a null hypothesis and an alternative hypothesis. This basic statistical tutorial discusses the appropriate use, including their so-called assumptions, of the common unadjusted bivariate tests for hypothesis testing and thus comparing study sample data for a difference or association. The appropriate choice of a statistical test is predicated on the type of data being analyzed and compared. The unpaired or independent samples t test is used to test the null hypothesis that the 2 population means are equal, thereby accepting the alternative hypothesis that the 2 population means are not equal. The unpaired t test is intended for comparing dependent continuous (interval or ratio) data from 2 study groups. A common mistake is to apply several unpaired t tests when comparing data from 3 or more study groups. In this situation, an analysis of variance with post hoc (posttest) intragroup comparisons should instead be applied. Another common mistake is to apply a series of unpaired t tests when comparing sequentially collected data from 2 study groups. In this situation, a repeated-measures analysis of variance, with tests for group-by-time interaction, and post hoc comparisons, as appropriate, should instead be applied in analyzing data from sequential collection points. The paired t test is used to assess the difference in the means of 2 study groups when the sample observations have been obtained in pairs, often before and after an intervention in each study subject. The Pearson chi-square test is widely used to test the null hypothesis that 2 unpaired categorical variables, each with 2 or more nominal levels (values), are independent of each other. When the null hypothesis is rejected, 1 concludes that there is a probable association between the 2 unpaired categorical variables. When comparing 2 groups on an ordinal or nonnormally distributed continuous outcome variable, the 2-sample t test is usually not appropriate. The Wilcoxon-Mann-Whitney test is instead preferred. When making paired comparisons on data that are ordinal, or continuous but nonnormally distributed, the Wilcoxon signed-rank test can be used. In analyzing their data, researchers should consider the continued merits of these simple yet equally valid unadjusted bivariate statistical tests. However, the appropriate use of an unadjusted bivariate test still requires a solid understanding of its utility, assumptions (requirements), and limitations. This understanding will mitigate the risk of misleading findings, interpretations, and conclusions.

http://ift.tt/2kh20oB

Anesthesia & Analgesia: Update and a Year in Review

No abstract available

http://ift.tt/2kh1YNv

A Novel Method of Evaluating Key Factors for Success in a Multifaceted Critical Care Fellowship Using Data Envelopment Analysis

BACKGROUND: The current system of summative multi-rater evaluations and standardized tests to determine readiness to graduate from critical care fellowships has limitations. We sought to pilot the use of data envelopment analysis (DEA) to assess what aspects of the fellowship program contribute the most to an individual fellow's success. DEA is a nonparametric, operations research technique that uses linear programming to determine the technical efficiency of an entity based on its relative usage of resources in producing the outcome. DESIGN: Retrospective cohort study. SUBJECTS AND SETTING: Critical care fellows (n = 15) in an Accreditation Council for Graduate Medical Education (ACGME) accredited fellowship at a major academic medical center in the United States. METHODS: After obtaining institutional review board approval for this retrospective study, we analyzed the data of 15 anesthesiology critical care fellows from academic years 2013–2015. The input-oriented DEA model develops a composite score for each fellow based on multiple inputs and outputs. The inputs included the didactic sessions attended, the ratio of clinical duty works hours to the procedures performed (work intensity index), and the outputs were the Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP) score and summative evaluations of fellows. RESULTS: A DEA efficiency score that ranged from 0 to 1 was generated for each of the fellows. Five fellows were rated as DEA efficient, and 10 fellows were characterized in the DEA inefficient group. The model was able to forecast the level of effort needed for each inefficient fellow, to achieve similar outputs as their best performing peers. The model also identified the work intensity index as the key element that characterized the best performers in our fellowship. CONCLUSIONS: DEA is a feasible method of objectively evaluating peer performance in a critical care fellowship beyond summative evaluations alone and can potentially be a powerful tool to guide individual performance during the fellowship.

http://ift.tt/2kgq8aO

Inadvertent Perioperative Hypothermia Induced by Spinal Anesthesia for Cesarean Delivery Might Be More Significant Than We Think: Are We Doing Enough to Warm Our Parturients?

No abstract available

http://ift.tt/2kK0n1V

Society for Obstetric Anesthesia and Perinatology 2017 Meeting Report

No abstract available

http://ift.tt/2kK0kDh

Efficiency, Paths, Goals, and Frontiers in Graduate Education: New Uses for Old Concepts

No abstract available

http://ift.tt/2kITbTL

Pentathol Postcards: Erratum

No abstract available

http://ift.tt/2kh1NSl

Repeated Administration of Duloxetine Suppresses Neuropathic Pain by Accumulating Effects of Noradrenaline in the Spinal Cord

BACKGROUND: Antidepressants are used to treat neuropathic pain and although the detailed mechanisms of their effects are unclear, the descending noradrenergic inhibitory system might play an important role. We tested our hypothesis that repeated administration of duloxetine suppresses neuropathic pain by restoring the descending noradrenergic inhibitory system in rats 6 weeks after spinal nerve ligation (SNL). METHODS: We subcutaneously injected SNL rats with duloxetine (10 mg kg−1 day−1) daily for 3 consecutive days and assessed behavioral hypersensitivity and noxious stimulus–induced analgesia (NSIA) activated by subcutaneous injection of capsaicin. We also performed microdialysis studies of the spinal cord, noradrenaline measurements of homogenized lumbar spinal tissue, and immunohistochemistry of the locus coeruleus. RESULTS: Three daily injections of duloxetine attenuated the mechanical hyperalgesia induced by SNL (SNL treated with vehicle: 88 ± 9.4 g versus SNL treated with duloxetine: 148 ± 13 g, P

http://ift.tt/2kK0ieD

Anaesthesia for the Elderly Patient, 2nd ed.

No abstract available

http://ift.tt/2kLDJGq

Postoperative Atrial Fibrillation and Maslow’s Hammer

No abstract available

http://ift.tt/2kgq7DM

In Response

No abstract available

http://ift.tt/2kLDH1g

The Pediatric Elephant in the Room

No abstract available

http://ift.tt/2kePF4j

Risk of Cognitive Impairment by Sleep-Disordered Breathing

No abstract available

http://ift.tt/2kHwGP8

The Eye of the Beholder

No abstract available

http://ift.tt/2kf0tiM

Preventing Mistransfusions: An Evaluation of Institutional Knowledge and a Response

BACKGROUND: Blood product mistransfusions occur when a process error causes transfusion of incompatible blood products. These events are known sources of negative patient outcomes. One such event demonstrated an institutional knowledge gap and an opportunity to reduce this source of transfusion errors. The focus of this study was to evaluate the application of point of care cognitive aids to bridge potentially lethal knowledge gaps in blood product to patient compatibility. METHODS: A patient-donor ABO antigen compatibility grid for red blood cells (RBC) and fresh frozen plasma (FFP) was developed for creation of a cognitive aid and a blood product safety quiz. Participants included 117 registered nurses and postgraduate medical interns who were given 2 minutes to complete the quiz for establishing institutional controls. A separate group of 111 registered nurses and interns were given the same timed quiz twice, without and then with a blood product compatibility cognitive aid. An analysis of covariance was used to evaluate without cognitive aid versus with cognitive aid quiz results while taking the specialty (nurse versus interns) and baseline score into consideration. The blood bank adopted the grid as a forcing function to be completed before release of blood products. RESULTS: The correct RBC answer percentage increased from 84.7% to 98.3% without and with cognitive aid (average improvement 13.6%, standard deviation [SD] = 18.3%, 95% confidence interval, 10.1%–17.1%, P

http://ift.tt/2kfYOJX

Insight Into Our Technologies: A New Series of Manuscripts in Anesthesia & Analgesia

No abstract available

http://ift.tt/2kgwS8M

Measurement Under the Microscope: High Variability and Limited Construct Validity in Emergency Department Patient-Experience Scores

We evaluate variability and construct validity in commercially generated patient-experience survey data in a large sample of US emergency departments (EDs).

http://ift.tt/2oEvmly

Does Cognitive Training Prevent Cognitive Decline? A Systematic Review

Background:

Structured activities to stimulate brain function—that is, cognitive training exercises—are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated.

Purpose:

To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI).

Data Sources:

Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches.

Study Selection:

Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia.

Data Extraction:

Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed.

Data Synthesis:

Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported.

Limitation:

Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias.

Conclusion:

In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient.

Primary Funding Source:

Agency for Healthcare Research and Quality.

http://ift.tt/2yU6tSI

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia A Systematic Review

Background:

The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems.

Purpose:

To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments.

Data Sources:

Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews.

Study Selection:

Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls.

Data Extraction:

Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.

Data Synthesis:

Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions.

Limitation:

Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes.

Conclusion:

Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence).

Primary Funding Source:

Agency for Healthcare Research and Quality.

http://ift.tt/2yU3pGb

Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia A Systematic Review

Background:

Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain.

Purpose:

To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis.

Data Sources:

Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews.

Study Selection:

English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls.

Data Extraction:

Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.

Data Synthesis:

Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B₁₂ was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported.

Limitation:

Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures.

Conclusion:

Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.

Primary Funding Source:

Agency for Healthcare Research and Quality.

http://ift.tt/2B9rHC1

Prevention of Late-Life Dementia: No Magic Bullet

In 4 evidence-based reviews from the Minnesota Evidence-based Practice Center, the authors summarize findings from randomized controlled trials on the effectiveness of interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia. The editorialist discusses the findings in light of recent related reports on the issue. He concludes that although there is no magic bullet to prevent dementia, multicomponent interventions that promote a healthy lifestyle hold some promise.

http://ift.tt/2yU6jL6

Prolonged Asystole After a Loading Dose of Ticagrelor

http://ift.tt/2Bd0s9q

The Healthy User Effect in Studies of Statins in the Critically Ill

No abstract available

http://ift.tt/2Bazj7d

Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis

Objectives: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy. Data Sources: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched. Study Selection: Articles not in English, pediatric studies, and case reports were excluded. Data Extraction: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3. Data Synthesis: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, –1.30; 95% CI, –3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57–4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83–3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97–3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48–20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83–2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86–2.11). Conclusions: The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.

http://ift.tt/2Bbij0u

Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury

Objectives: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal PO2 in ovine sepsis. We also assessed the validity of urinary PO2 as a surrogate measure of medullary PO2. Design: Interventional study. Setting: Research Institute. Subjects: Sixteen adult Merino ewes (n = 8/group). Interventions: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure PO2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24–30 hours, angiotensin II (0.5–33.0 ng/kg/min) or saline vehicle was infused. Measurements and Main Results: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary PO2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary PO2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia. Conclusions: In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary PO2 may be used to detect medullary hypoxia.

http://ift.tt/2BaIk0d

Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration*

Objective: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. Design: Retrospective subgroup analysis of randomized controlled trial. Setting: Multicenter North American and European clinical trial. Patients: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. Interventions: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours. Measurements and Main Results: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, –0.12; 95% CI, –0.23 to –0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, –0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant. Conclusions: We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.

http://ift.tt/2Bd94Np

Hyponatremic Encephalopathy

No abstract available

http://ift.tt/2yTO73W

Respiratory Viruses in Invasively Ventilated Critically Ill Patients—A Prospective Multicenter Observational Study

Objectives: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. Design: Prospective observational study. Setting: Five ICUs in the Netherlands. Patients: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. Interventions: None. Measurements and Main Results: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non–severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non–severe acute respiratory infection (p

http://ift.tt/2yUAbH6

Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome*

Objectives: The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Design: Prospective observational cohort study. Setting: University affiliated PICU. Patients: Mechanically ventilated children with acute respiratory distress syndrome. Interventions: Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. Measurements and Main Results: In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p

http://ift.tt/2yUkOhR

Sepsis Survivors Admitted to Skilled Nursing Facilities: Cognitive Impairment, Activities of Daily Living Dependence, and Survival*

Objective: Severe sepsis survivors frequently experience cognitive and physical functional impairment. The degree of impairment and its association with mortality is understudied, particularly among those discharged to a skilled nursing facility. Our objective was to quantify the cognitive and physical impairment among severe sepsis survivors discharged to a skilled nursing facility and to investigate the relationship between impairment and long-term mortality. Design: Retrospective cohort study. Setting: United States. Subjects: Random 5% sample of Medicare patients discharged following severe sepsis hospitalization, 2005–2009 (n = 135,370). Measurement and Main Results: Medicare data were linked with the Minimum Data Set; Minimum Data Set-Cognition Scale was used to assess cognitive function, and the Minimum Data Set activities of daily living hierarchical scale was used to assess functional dependence. Associations were evaluated using multivariable logistic regression, Kaplan-Meier curves, and Cox proportional hazards regression. Of 66,540 beneficiaries admitted to a skilled nursing facility following severe sepsis, 34% had severe or very severe cognitive impairment, and 72.5% had maximal, dependence, or total dependence in activities of daily living. Median survival was 19.4 months for those discharged to a skilled nursing facility without having been in a skilled nursing facility in the preceding 1 year and 10.4 months for those discharged to a skilled nursing facility who had spent time in a skilled nursing facility in the prior year. The adjusted hazard ratio for death was 3.1 for those with very severe cognitive impairment relative to those who were cognitively intact (95% CI, 2.9–3.2; p

http://ift.tt/2yUkKyD

Racial and Geographic Disparities in Interhospital ICU Transfers*

Objectives: Interhospital transfer, a common intervention, may be subject to healthcare disparities. In mechanically ventilated patients with sepsis, we hypothesize that disparities not disease related would be found between patients who were and were not transferred. Design: Retrospective cohort study. Setting: Nationwide Inpatient Sample, 2006–2012. Patients: Patients over 18 years old with a primary diagnosis of sepsis who underwent mechanical ventilation. Interventions: None. Measurements and Main Results: We obtained age, gender, length of stay, race, insurance coverage, do not resuscitate status, and Elixhauser comorbidities. The outcome used was interhospital transfer from a small- or medium-sized hospital to a larger acute care hospital. Of 55,208,382 hospitalizations, 46,406 patients met inclusion criteria. In the multivariate model, patients were less likely to be transferred if the following were present: older age (odds ratio, 0.98; 95% CI, 0.978–0.982), black race (odds ratio, 0.79; 95% CI, 0.70–0.89), Hispanic race (odds ratio, 0.79; 95% CI, 0.69–0.90), South region hospital (odds ratio, 0.79; 95% CI, 0.72–0.88), teaching hospital (odds ratio, 0.31; 95% CI, 0.28–0.33), and do not resuscitate status (odds ratio, 0.19; 95% CI, 0.15–0.25). Conclusions: In mechanically ventilated patients with sepsis, we found significant disparities in race and geographic location not explained by medical diagnoses or illness severity.

http://ift.tt/2ySSTyJ

Nebulized Versus IV Amikacin as Adjunctive Antibiotic for Hospital and Ventilator-Acquired Pneumonia Postcardiac Surgeries: A Randomized Controlled Trial*

Objective: Nebulized antibiotics offer high efficacy due to significant local concentrations and safety with minimal blood levels. This study evaluates the efficacy and nephrotoxicity of nebulized versus IV amikacin in postcardiothoracic surgical patients with nosocomial pneumonia caused by multidrug-resistant Gram- negative bacilli. Design: Prospective, randomized, controlled study on surgical patients divided into two groups. Setting: Postcardiac surgery ICU. Interventions: The first gtroup was administered IV amikacin 20 mg/kg once daily. The second group was prescribed amikacin nebulizer 400 mg twice daily. Both groups were co-administered IV piperacillin/tazobactam empirically. Patients: Recruited patients were diagnosed by either hospital-acquired pneumonia or ventilator-associated pneumonia where 56 (42.1%) patients were diagnosed with hospital-acquired pneumonia, 51 (38.34%) patients were diagnosed with early ventilator-associated pneumonia, and 26 (19.54%) patients with late ventilator-associated pneumonia. Measurements and Main Results: Clinical cure in both groups assessed on day 7 of treatment was the primary outcome. Efficacy was additionally evaluated through assessing the length of hospital stay, ICU stay, days on amikacin, days on mechanical ventilator, mechanical ventilator-free days, days to reach clinical cure, and mortality rate. Lower nephrotoxicity in the nebulized group was observed through significant preservation of kidney function (p

http://ift.tt/2yTxk14

Calcium Channel Blockers and Sepsis Outcomes

No abstract available

http://ift.tt/2BcVDgk

Safety and Feasibility of Early Physical Therapy for Patients on Extracorporeal Membrane Oxygenator: University of Maryland Medical Center Experience*

Objectives: To examine the feasibility and safety of mobilizing patients while on extracorporeal membranous oxygenation support. Design: Retrospective cohort study. Setting: Medical and Surgical ICUs in a large tertiary care hospital in the United States. Patients: Adults supported on extracorporeal membranous oxygenation from January 2014 to December 2015. Measurements and Main Results: We reviewed the medical records from physical therapy, perfusion, and intensivists to obtain the number and type of physical therapy interventions and discharge status; extracorporeal membranous oxygenation type and description of support, cannulation sites; and risk management details of adverse effects, if any. Of 254 patients supported on extracorporeal membranous oxygenation, 167 patients (66.7%) received a total of 607 physical therapy sessions while on extracorporeal membranous oxygenation support. In this cohort, 134 patients (80.2%) had at least one femoral cannula during physical therapy intervention. Sixty-six of the 167 patients (39.5%) were supported on extracorporeal membranous oxygenation with bifemoral cannulas, and 44 (26.3%) were on veno-arterial extracorporeal membranous oxygenation. A dual lumen catheter was only used in five cases. Twenty-five patients (15%) (13 bifemoral cases) participated in standing or ambulation activities. Seventy-five patients (68.8%) who were successfully weaned from extracorporeal membranous oxygenation were discharged to a rehabilitation facility; 26 patients (23.8%) went home. Three minor events (

http://ift.tt/2Bb94ha

Gazing Into the Crystal Ball or Looking Through the Rear View Mirror? Prediction of Neurologic Outcome in Survivors of Pediatric Critical Illness*

No abstract available

http://ift.tt/2yTOb3G

Perceptions of Risk and Safety in the ICU: A Qualitative Study of Cognitive Processes Relating to Staffing*

Objectives: The aims of this study were to 1) examine individual professionals' perceptions of staffing risks and safe staffing in intensive care and 2) identify and examine the cognitive processes that underlie these perceptions. Design: Qualitative case study methodology with nurses, doctors, and physiotherapists. Setting: Three mixed medical and surgical adult ICUs, each on a separate hospital site within a 1,200-bed academic, tertiary London hospital group. Subjects: Forty-four ICU team members of diverse professional backgrounds and seniority. Interventions: None. Main Results: Four themes (individual, team, unit, and organizational) were identified. Individual care provision was influenced by the pragmatist versus perfectionist stance of individuals and team dynamics by the concept of an "A" team and interdisciplinary tensions. Perceptions of safety hinged around the importance of achieving a "dynamic balance" influenced by the burden of prevailing circumstances and the clinical status of patients. Organizationally, professionals' risk perceptions affected their willingness to take personal responsibility for interactions beyond the unit. Conclusions: This study drew on cognitive research, specifically theories of cognitive dissonance, psychological safety, and situational awareness to explain how professionals' cognitive processes impacted on ICU behaviors. Our results may have implications for relationships, management, and leadership in ICU. First, patient care delivery may be affected by professionals' perfectionist or pragmatic approach. Perfectionists' team role may be compromised and they may experience cognitive dissonance and subsequent isolation/stress. Second, psychological safety in a team may be improved within the confines of a perceived "A" team but diminished by interdisciplinary tensions. Third, counter intuitively, higher "situational" awareness for some individuals increased their stress and anxiety. Finally, our results suggest that professionals have varying concepts of where their personal responsibility to minimize risk begins and ends, which we have termed "risk horizons" and that these horizons may affect their behavior both within and beyond the unit.

http://ift.tt/2yUCp9f

Escalations in Care: Do Interhospital Transfers Lead to Greener Pastures?*

No abstract available

http://ift.tt/2Ba8fFl

Significance of Mini Bronchoalveolar Lavage Fluid Amylase Level in Ventilator-Associated Pneumonia: A Prospective Observational Study*

Objectives: Aspiration of oropharyngeal or gastric contents in intubated patients can lead to ventilator-associated pneumonia. Amylase in respiratory secretion has been reported as a possible marker of aspiration. We studied whether elevated α-amylase in mini bronchoalveolar lavage specimens can be suggestive of ventilator-associated pneumonia in intubated patients with high clinical suspicion. Design: Prospective single-center observational study. Setting: Department of Critical Care Medicine, tertiary care academic institute. Patients: Adult patients on mechanical ventilation for more than 48 hours with with clinically suspected ventilator-associated pneumonia as per defined criteria, admitted between December 2014 and May 2016. Methods: Mini bronchoalveolar lavage samples were collected within 72 hours of endotracheal intubation. Samples were sent for α-amylase level assay and quantitative culture. Ventilator-associated pneumonia was confirmed from mini bronchoalveolar lavage microbial culture of greater than or equal to 104 cfu/mL, and patients were divided into ventilator-associated pneumonia and no ventilator-associated pneumonia groups. Pre- and postintubation risk factors for aspiration were also noted. Results: The prevalence of ventilator-associated pneumonia was 64.9% among 151 patients in whom it was clinically suspected. Median (interquartile range) mini bronchoalveolar lavage α-amylase levels in ventilator-associated pneumonia and no ventilator-associated pneumonia groups on the day of study inclusion were 287 U/L (164–860 U/L) and 94 U/L (59–236 U/L), respectively (p

http://ift.tt/2BakZMa

Influence of Postoperative Thrombosis Prophylaxis on the Recurrence of Chronic Subdural Hematoma After Burr-Hole Drainage

Objectives: Chronic subdural hematoma is a commonly encountered disease in neurosurgic practice, whereas its increasing prevalence is compatible with the ageing population. Recommendations concerning postoperative thrombosis prophylaxis after burr-hole drainage of chronic subdural hematoma are lacking. The aim of this study was to analyze the correlation between recurrence of chronic subdural hematoma and postoperative application of thrombosis prophylaxis. Design: Retrospective, consecutive sample of patients undergoing burr-hole drainage for chronic subdural hematoma over 3 years. Setting: Single, academic medical center. Patients: All patients undergoing surgical evacuation of a chronic subdural hematoma with burr-hole drainage. Exclusion: patients under the age of 18 years, who presented with an acute subdural hematoma and those who underwent a craniotomy. Interventions: We compared patients receiving thrombosis prophylaxis treatment after burr-hole drainage of chronic subdural hematoma with those who were not treated. Primary outcome measure was reoperation of chronic subdural hematoma due to recurrence. Secondary outcome measures were thromboembolic and cardiovascular events, hematologic findings, morbidity, and mortality. In addition, a subanalysis comparing recurrence rate dependent on the application time of thrombosis prophylaxis ( 48 hr) was undertaken. Measurements and Main Results: Overall recurrence rate of chronic subdural hematoma was 12.7%. Out of the 234 analyzed patients, 135 (57.3%) received postoperative thrombosis prophylaxis (low-molecular-weight heparin) applied subcutaneously. Recurrence of chronic subdural hematoma occurred in the thrombosis prophylaxis group and control group in 12 patients (8.9%) and 17 patients (17.2%), respectively, showing no significant difference (odds ratio, 0.47 [95% CI, 0.21 – 1.04]). A subanalysis comparing recurrence rate of chronic subdural hematoma dependent on the application time of thrombosis prophylaxis ( 48 hr) showed no significant difference either (odds ratio, 2.80 [95% CI, 0.83–9.36]). Higher dosage of thrombosis prophylaxis correlated with recurrence rates of chronic subdural hematoma, both in univariate and multivariate analyses. Conclusions: Our data suggest that the application of postoperative thrombosis prophylaxis after burr-hole drainage for chronic subdural hematoma does not result in higher recurrence rates of chronic subdural hematoma. In addition, it seems that early administration of thrombosis prophylaxis (

http://ift.tt/2B9Fng7

Development and Validation of an Abbreviated Questionnaire to Easily Measure Cognitive Failure in ICU Survivors: A Multicenter Study

Objectives: To develop and validate an abbreviated version of the Cognitive Failure Questionnaire that can be used by patients as part of self-assessment to measure functional cognitive outcome in ICU survivors. Design: A retrospective multicenter observational study. Setting: The ICUs of two Dutch university hospitals. Patients: Adult ICU survivors. Interventions: None. Measurements and Main Results: Cognitive functioning was evaluated between 12 and 24 months after ICU discharge using the full 25-item Cognitive Failure Questionnaire (CFQ-25). Incomplete CFQ-25 questionnaires were excluded from analysis. Forward selection in a linear regression model was used in hospital A to assess which of the CFQ-25 items should be included to prevent a significant loss of correlation between an abbreviated and the full CFQ-25. Subsequently, the performance of an abbreviated Cognitive Failure Questionnaire was determined in hospital B using Pearson's correlation. A Bland-Altman plot was used to examine whether the reduced-item outcome scores of an abbreviated Cognitive Failure Questionnaire were a replacement for the full CFQ-25 outcome scores. Among 1,934 ICU survivors, 1,737 were included, 819 in hospital A, 918 in hospital B. The Pearson's correlation between the abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14) and the CFQ-25 was 0.99. The mean of the difference scores was –0.26, and 95% of the difference scores fell within +5 and –5.5 on a 100-point maximum score. Conclusions: It is feasible to use the abbreviated CFQ-14 to measure self-reported cognitive failure in ICU survivors as this questionnaire has a similar performance as the full CFQ-25.

http://ift.tt/2Bazdwn

A Mixed Lipid Emulsion for Prevention of Parenteral Nutrition Associated Cholestasis in Extremely Low Birth Weight Infants: A Randomized Clinical Trial

To examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants.

http://ift.tt/2oDskxL

Car Seat Tolerance Screening in the Neonatal Intensive Care Unit: Failure Rates, Risk Factors, and Adverse Outcomes

To characterize the epidemiology of Car Seat Tolerance Screening (CSTS) failure and the association between test failure and all-cause 30-day postdischarge mortality or hospital readmission in a large, multicenter cohort of preterm infants receiving neonatal intensive care.

http://ift.tt/2CWAuVb

Heterozygous Deletion Impacting SMARCAD1 in the Original Kindred with Absent Dermatoglyphs and Associated Features (Baird, 1964)

In 1964, Baird described a family with adermatoglyphia, facial milia, and skin fragility. Using whole exome sequencing, genotyping, and Sanger sequencing, we identified a 116-kb heterozygous deletion involving exons 1-9 of SMARCAD1 in descendants of this kindred. This contrasts with point mutations within exon 9 in all other reported families.

http://ift.tt/2oEluIw

The Contemporary Bacteriologic Epidemiology of Osteoarticular Infections in Children in Switzerland

To assess the contemporary bacteriologic epidemiology of pediatric osteoarticular infection with particular regard to children's ages, because Kingella kingae has gained increasing recognition as the predominant pathogen for osteoarticular infection in young children.

http://ift.tt/2CYugUM

Understanding the Burden of Pediatric Gastrointestinal Diseases—Does a Look From the Perspective of Inpatient Administrative Databases Help?

Gastrointestinal (GI) diseases affect millions of US residents each year; recent studies estimate 4.6 million hospitalizations and $142 billion per year in both direct and indirect health costs.1 Studies of the national burden of GI diseases, however, have not been specific to the pediatric population. Because the most common GI diseases in hospitalized children (acute diarrhea, appendicitis, general abdominal pain, esophageal disorders) are different from those of adults (gallbladder disease, diverticular disease, pancreatitis),2,3 the cost burden of GI diseases also is distinct in children.

http://ift.tt/2oIXnIs

Intracranial Complications of Sinusitis

A 5-year-old girl being treated with antibiotics for a recent history of presumptive acute rhinosinusitis presented with recurrence of fever, lethargy, and subacute onset of left lower extremity weakness. On physical examination, she was noted to have neck stiffness and flaccid weakness of the left lower limb, but preserved deep tendon reflexes. Neurologic examination was otherwise unremarkable, including funduscopic examination. Peripheral white blood cell count was markedly elevated at 27 000, with a predominance of neutrophils, and the C-reactive protein value was elevated at 127.

http://ift.tt/2CZWnmf

After PCI in AF, dual antithrombotic therapy with dabigatran reduced bleeding compared with triple therapy

http://ift.tt/2BxtVIt

Liraglutide reduced a composite renal outcome at a median 4 y in patients with type 2 diabetes and high CV risk

http://ift.tt/2Bv5OKh

Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice A Retrospective Cohort Study

Background:

Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited.

Objective:

To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice.

Design:

Retrospective cohort.

Setting:

National U.S. Food and Drug Administration Sentinel network.

Patients:

Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014.

Measurements:

Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score–matched patients starting treatment with dabigatran or warfarin.

Results:

Among 25 289 patients starting dabigatran therapy and 25 289 propensity score–matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran.

Limitation:

Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values).

Conclusion:

In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation.

Primary Funding Source:

U.S. Food and Drug Administration.

http://ift.tt/2CBaCgr

Review: Weak evidence of benefits of cannabis for chronic neuropathic pain; moderate to weak evidence of adverse effects

http://ift.tt/2BvuEtF

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening A Case–Control Study

Background:

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement.

Objective:

To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas.

Design:

Case–control study.

Setting:

Colonoscopy-controlled referral population from several centers.

Participants:

315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples).

Measurements:

Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples.

Results:

In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001).

Limitation:

Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples.

Conclusion:

Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening.

Primary Funding Source:

Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

http://ift.tt/2B04kK5

Annals Story Slam - I Don't Think It's a Good Fit

http://ift.tt/2Bxjog0

Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital Settings A Systematic Review

Background:

Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain.

Purpose:

To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone.

Data Sources:

Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists.

Study Selection:

English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms.

Data Extraction:

Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE).

Data Synthesis:

Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment.

Limitation:

There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations.

Conclusion:

Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport.

Primary Funding Source:

Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891)

http://ift.tt/2j83uEl

Pharmacologic Treatment of Seasonal Allergic Rhinitis: Synopsis of Guidance From the 2017 Joint Task Force on Practice Parameters

Description:

The Joint Task Force on Practice Parameters, which comprises representatives of the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI), formed a workgroup to review evidence and provide guidance to health care providers on the initial pharmacologic treatment of seasonal allergic rhinitis in patients aged 12 years or older.

Methods:

To update a prior systematic review, the workgroup searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 18 July 2012 to 29 July 2016 to identify studies that addressed efficacy and adverse effects of single or combination pharmacotherapy for seasonal allergic rhinitis. In conjunction with the Joint Task Force, the workgroup reviewed the evidence and developed recommendations about initial treatment approaches by using the Grading of Recommendations Assessment, Development and Evaluation approach. Members of the AAAAI, the ACAAI, and the general public provided feedback on the draft document, which the Joint Task Force reviewed before finalizing the guideline.

Recommendation 1:

For initial treatment of seasonal allergic rhinitis in persons aged 12 years or older, routinely prescribe monotherapy with an intranasal corticosteroid rather than an intranasal corticosteroid in combination with an oral antihistamine. (Strong recommendation)

Recommendation 2:

For initial treatment of seasonal allergic rhinitis in persons aged 15 years or older, recommend an intranasal corticosteroid over a leukotriene receptor antagonist. (Strong recommendation)

Recommendation 3:

For treatment of moderate to severe seasonal allergic rhinitis in persons aged 12 years or older, the clinician may recommend the combination of an intranasal corticosteroid and an intranasal antihistamine for initial treatment. (Weak recommendation)

http://ift.tt/2zytify