bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivering on the Promise of CLER: A Patient Safety Rotation That Aligns Resident Education With Hospital Processes
Authors: Patel Ekta , Muthusamy Veena , Young John Q.
Published: January 2018

Problem

Residency programs must provide training in patient safety. Yet, significant gaps exist among published patient safety curricula. The authors developed a rotation designed to be scalable to an entire residency, built on sound pedagogy, aligned with hospital safety processes, and effective in improving educational outcomes.

Approach

From July 2015 to May 2017, each second-year resident completed the two-week rotation. Residents engaged the foundational science asynchronously via multiple modalities and then practiced applying key concepts during a mock root cause analysis. Next, each resident performed a special review of an actual adverse patient event and presented findings to the hospital’s Special Review Committee (SRC). Multiple educational outcomes were assessed, including resident satisfaction and attitudes (postrotation survey), changes in knowledge via pre- and posttest, quality of the residents’ written safety analyses and oral presentations (per survey of SRC members), and organizational changes that resulted from the residents’ reviews.

Outcomes

Twenty-two residents completed the rotation. Most components were rated favorably; 80% (12/15 respondents) indicated interest in future patient safety work. Knowledge improved by 44.3% (P < .0001; pretest mean 23.7, posttest mean 34.2). Compared to faculty, SRC members rated the quality of residents’ written reviews as superior and the quality of the rated oral presentations as either comparable or superior. The reviews identified a variety of safety vulnerabilities and led to multiple corrective actions.

Next Steps

The authors will evaluate the curriculum in a controlled trial with better measures of change in behavior. Further tests of the curriculum’s scalability to other contexts are needed.
A Narrative Review of Cardiovascular Abnormalities After Spontaneous Intracerebral Hemorrhage
Authors: Lele Abhijit , Lakireddy Viharika , Gorbachov Sergii , Chaikittisilpa Nophanan , Krishnamoorthy Vijay , Vavilala Monica S.
Published: January 2018

Background:

The recommended cardiac workup of patients with spontaneous intracerebral hemorrhage (ICH) includes an electrocardiogram (ECG) and cardiac troponin. However, abnormalities in other cardiovascular domains may occur. We reviewed the literature to examine the spectrum of observed cardiovascular abnormalities in patients with ICH.

Methods:

A narrative review of cardiovascular abnormalities in ECG, cardiac biomarkers, echocardiogram, and hemodynamic domains was conducted on patients with ICH.

Results:

We searched PubMed for articles using MeSH Terms “heart,” “cardiac,” hypertension,” “hypotension,” “blood pressure,” “electro,” “echocardio,” “troponin,” “beta natriuretic peptide,” “adverse events,” “arrhythmi,” “donor,” “ICH,” “intracerebral hemorrhage.” Using Covidence software, 670 articles were screened for title and abstracts, 482 articles for full-text review, and 310 extracted. A total of 161 articles met inclusion and exclusion criteria, and, included in the manuscript. Cardiovascular abnormalities reported after ICH include electrocardiographic abnormalities (56% to 81%) in form of prolonged QT interval (19% to 67%), and ST-T changes (19% to 41%), elevation in cardiac troponin (>0.04 ng/mL), and beta-natriuretic peptide (BNP) (>156.6 pg/mL, up to 78%), echocardiographic abnormalities in form of regional wall motion abnormalities (14%) and reduced ejection fraction. Location and volume of ICH affect the prevalence of cardiovascular abnormalities. Prolonged QT interval, elevated troponin-I, and BNP associated with increased in-hospital mortality after ICH. Blood pressure control after ICH aims to preserve cerebral perfusion pressure and maintain systolic blood pressure between 140 and 179 mm Hg, and avoid intensive blood pressure reduction (110 to 140 mm Hg). The recipients of ICH donor hearts especially those with reduced ejection fraction experience increased early mortality and graft rejection.

Conclusions:

Various cardiovascular abnormalities are common after spontaneous ICH. The workup of patients with spontaneous ICH should involve 12-lead ECG, cardiac troponin-I, as well as BNP, and echocardiogram to evaluate for heart failure. Blood pressure control with preservation of cerebral perfusion pressure is a cornerstone of hemodynamic management after ICH. The perioperative implications of hemodynamic perturbations after ICH warrant urgent further examination.
Quantitative Assessment of Knee Progression Angle During Gait in Children With Cerebral Palsy
Authors: Davids Jon R. , Cung Nina Q. , Pomeroy Robin , Schultz Brooke , Torburn Leslie , Kulkarni Vedant A. , Brown Sean , Bagley Anita M.
Published: January 2018

Background:

Abnormal hip rotation is a common deviation in children with cerebral palsy (CP). Clinicians typically assess hip rotation during gait by observing the direction that the patella points relative to the path of walking, which is referred to as the knee progression angle (KPA). Two kinematic methods for calculating the KPA are compared with each other. Video-based qualitative assessment of KPA is compared with the quantitative methods to determine reliability and validity.

Methods:

The KPA was calculated by both direct and indirect methods for 32 typically developing (TD) children and a convenience cohort of 43 children with hemiplegic type CP. An additional convenience cohort of 26 children with hemiplegic type CP was selected for qualitative assessment of KPA, performed by 3 experienced clinicians, using 3 categories (internal, >10 degrees; neutral, −10 to 10 degrees; and external, >−10 degrees).

Results:

Root mean square (RMS) analysis comparing the direct and indirect KPAs was 1.14+0.43 degrees for TD children, and 1.75+1.54 degrees for the affected side of children with CP. The difference in RMS among the 2 groups was statistically, but not clinically, significant (P=0.019). Intraclass correlation coefficient revealed excellent agreement between the direct and indirect methods of KPA for TD and CP children (0.996 and 0.992, respectively; P<0.001).

For the qualitative assessment of KPA there was complete agreement among all examiners for 17 of 26 cases (65%). Direct KPA matched for 49 of 78 observations (63%) and indirect KPA matched for 52 of 78 observations (67%).

Conclusions:

The RMS analysis of direct and indirect methods for KPA was statistically but not clinically significant, which supports the use of either method based upon availability. Video-based qualitative assessment of KPA showed moderate reliability and validity. The differences between observed and calculated KPA indicate the need for caution when relying on visual assessments for clinical interpretation, and demonstrate the value of adding KPA calculation to standard kinematic analysis.

Level of Evidence:

Level II—diagnostic test.
Harms of cigarette smoking: call to increase knowledge among children
Authors: Lonergan Bradley , Harding Victoria , Cohen Hannah , Wylleman Elisa , Cohen Richard , Stebbing Justin
Published: January 2018

Although the major burden of disease caused by smoking is observed in the adult population, two-third of smokers start before the age of 18 years. Reducing the number of young smokers could lead to marked improvements to the health of the UK population and save billions of pounds in National Health Service finances. However, very little is known about what makes children decide to not smoke or to quit early. We believe that increased awareness of the health risks associated with smoking will reduce smoking uptake among children. This study identifies a significant lack of knowledge among children aged 11–17 years at two London secondary schools and potentially identifies an area for improving our antismoking programmes. Although 80% of pupils cited lung cancer as being a smoking-related disease, very few other conditions could be recalled. We must do all we can to reduce smoking uptake in children. Understanding their baseline knowledge is the first step towards addressing the deficits in our current antismoking programmes.
Screening for Depression in Pregnancy and the Postpartum Period
Authors: LEARMAN LEE A.
Published: January 2018

Depression in pregnancy and the postpartum period is common, burdensome, and underrecognized. Guidelines from multiple organizations support routine screening once during pregnancy and again in the postpartum period. A variety of validated patient questionnaires are effective screening tools for pregnant and postpartum women. Universal screening programs can successfully overcome patient, clinician, and system barriers and reduce the burden of disease. Novel approaches include postpartum screening in pediatric settings and the use of e-screening to optimize privacy and facilitate scoring and interpretation. Implementation of universal screening should be a priority for all health systems providing obstetrical care.
Impact of a Community-Based Healthy Lifestyle Program on Individuals With Traumatic Brain Injury
Authors: Driver Simon , Reynolds Megan , Woolsey Anne , Callender Librada , Prajapati Purvi K. , Bennett Monica , Kramer Kaye
Published: January 2018

Objectives:

To examine adherence with and effect of an evidence-based healthy lifestyle intervention modified for individuals with traumatic brain injury (TBI).

Design:

Pre-/postintervention without control.

Setting:

Community.

Participants:

Eighteen individuals with TBI: primarily male (61%), white (67%), with private insurance (50%). Mean age was 45.6 ± 12.3 years, weight 210 ± 42.6 lb, and body mass index 31.8 ± 4.6 (obese category) at baseline.

Interventions:

The primary goal of the Diabetes Prevention Program Group Lifestyle Balance program is 5% to 7% weight loss through increased physical activity and improved dietary behaviors.

Main Outcome Measure(s):

Adherence (ie, session attendance and self-monitoring of dietary behaviors), physiologic changes (ie, weight loss, blood pressure; waist and arm circumference; and lipid profile), and quality of life (ie, self-reported health, quality of life, and step count).

Results:

Average participant attendance (85% over 12 months) and self-monitoring (90% over 6 months) were high. Significant decreases were observed in diastolic blood pressure and waist and arm circumference from baseline through 12 months and from baseline to 3 months only for weight and total cholesterol. No significant changes were observed in self-reported health, quality of life, or step count.

Conclusions:

Participants demonstrated high adherence with the program, suggesting that individuals with TBI are able to successfully engage in the program and achieve significant weight loss and changes in key physiologic outcomes.
TRAUMATIC MACULAR HOLE CLOSURE AND VISUAL IMPROVEMENT AFTER TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUG TREATMENT
Authors: Li Albert S. , Ferrone Philip J.
Published: January 2018

Purpose:

To report a case of pediatric traumatic macular hole that closed with visual improvement after treatment with topical ketorolac.

Methods:

Retrospective case report.

Results:

A 15-year-old girl presented with persistent left blurred vision after being hit with a soccer ball 2 months before. Visual acuity was 20/40 with a full-thickness macular hole with cystoid macular edema. After treatment with ketorolac 0.4% four times a day for a month, the hole closed with resolution of the cystoid macular edema but some remaining subretinal fluid. The ketorolac was tapered over the following month, and the subretinal fluid resolved during the subsequent months. At 10 months after initial presentation, patient's vision was 20/20 with a normal foveal contour, no subretinal fluid, and minimal ellipsoid zone disruption.

Conclusion:

Topical nonsteroidal antiinflammatory drug treatment may play a role in the resolution of traumatic macular holes with cystoid macular edema.
AUTOSOMAL RECESSIVE BESTROPHINOPATHY: MULTIMODAL IMAGING UPDATE
Authors: Kalevar Ananda , Chen Judy J. , McDonald H. Richard , Fu Arthur D.
Published: January 2018

Background:

Autosomal recessive bestrophinopathy is part of the diverse spectrum of retinal diseases caused by mutations in the BEST1 gene.

Methods:

A case report.

Results:

We present a case that highlights the classic retinal findings of autosomal recessive bestrophinopathy with an emphasis on modern multimodal imaging.

Conclusion:

We describe modern multimodal imaging in an individual with a BEST1 gene mutation and clinical findings consistent with an autosomal recessive bestrophinopathy.
Involvement of Nectin–Afadin in the Adherens Junctions of the Corneal Endothelium
Authors: Okumura Naoki , Kagami Takato , Fujii Keita , Nakahara Makiko , Koizumi Noriko
Published: January 2018

Purpose:

The cell–cell adhesion molecules, cadherins and nectins, are involved in the formation of adherens junctions. However, involvement of nectins in the corneal endothelium has not yet been established. This study investigated the involvement of nectins in adherens junctions of the corneal endothelium.

Methods:

Nectin and cadherin expression in the corneal endothelium was evaluated by real-time polymerase chain reaction. Colocalization and direct binding of nectin-1 and N-cadherin to anchoring proteins (afadin and β-catenin, respectively) were determined by immunostaining and immunoprecipitation. The effect of afadin and N-cadherin knockdown on apical junctions was evaluated by immunostaining.

Results:

Real-time polymerase chain reaction confirmed nectin-1, nectin-2, nectin-3, nectin-4, and afadin expression in the corneal endothelium. Immunofluorescence staining showed colocalization of nectin and afadin at the basal side of the tight junction (where adherens junctions typically locate) and immunoprecipitation confirmed direct binding of nectin to afadin. N-cadherin, P-cadherin, VE-cadherin, and OB-cadherin messenger RNAs were expressed in the corneal endothelium. N-cadherin and β-catenin colocalized at the cell–cell border, where they directly bound and formed a cell–cell adhesion complex. N-cadherin knockdown disrupted the normal expression pattern of zonula occludens protein-1 and afadin, but afadin knockdown had no effect on the expression pattern of zonula occludens protein-1 and N-cadherin.

Conclusions:

We believe this to be the first report of conservation of the nectin–afadin system in the corneal endothelium and its involvement in the formation of adherens junctions. N-cadherin, as a member of the cadherin family, is also essential for the formation and maintenance of cell–cell adhesion mediated by nectins and tight junctions in the corneal endothelium.
Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study
Authors: Lass Jonathan H. , Benetz Beth Ann , Menegay Harry J. , Tsipis Constantinos P. , Cook Jane Caty , Boyer David S. , Singer Michael , Erickson Kristine , Saroj Namrata , Vitti Robert , Chu Karen W. , Moini Hadi , Soo Yuhwen , Cheng Yenchieh ,   on behalf of the RE-VIEW Study Investigators
Published: January 2018

Purpose:

The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration.

Methods:

RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52.

Results:

No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm2 at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm2 at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96).

Conclusions:

Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.
Clinical Characteristics and Risk Factors for Poor Outcome in Infants Less Than 90 Days of Age With Bacterial Meningitis in the United Kingdom and Ireland
Authors: Okike Ifeanyichukwu O. , Ladhani Shamez N. , Johnson Alan P. , Henderson Katherine L. , Blackburn Ruth M. , Muller-Pebody Berit , Cafferkey Mary , Anthony Mark , Ninis Nelly , Heath Paul T.
Published: January 2018

Background:

To describe the clinical characteristics and risk factors associated with poor outcome in infants <90 days of age with bacterial meningitis.

Methods:

Prospective, enhanced, national population-based active surveillance for infants <90 days of age with bacterial meningitis in the United Kingdom and Ireland between July 2010 and July 2011. Infants were identified through the British Paediatric Surveillance Unit, laboratory surveillance and meningitis charities.

Results:

Clinical details was available for 263 of 298 (88%) infants where a bacterium was identified, 184 (70%) were born at term. Fever was reported in 143 (54%), seizures in 73 (28%), bulging fontanelle in 58 (22%), coma in 15 (6%) and neck stiffness in 7 (3%). Twenty-three (9%) died and 56/240 (23%) of the survivors had serious central nervous system complications at discharge. Temperature instability [odds ratio (OR), 2.99; 95% confidence interval (CI): 1.21–7.41], seizures (OR, 7.06; 95% CI: 2.80–17.81), cerebrospinal fluid protein greater than the median concentration (2275 mg/dL; OR, 2.62; 95% CI: 1.13–6.10) and pneumococcal meningitis (OR, 4.83; 95% CI: 1.33–17.58) were independently associated with serious central nervous system complications while prematurity (OR, 5.84; 95% CI: 2.02–16.85), low birthweight (OR, 8.48; 95% CI: 2.60–27.69), coma at presentation (OR, 31.85; 95% CI: 8.46–119.81) and pneumococcal meningitis (OR, 4.62; 95% CI: 1.19–17.91) were independently associated with death.

Conclusions:

The classic features of meningitis were uncommon. The presentation in young infants is often nonspecific, and only half of cases presented with fever. A number of clinical and laboratory factors were associated with poor outcomes; further research is required to determine how knowledge of these risk factors might improve clinical management and outcomes.
Direct Echocardiographic Imaging of Berlin Heart Valves Can Aid in Early Detection of Berlin Heart Valve Dysfunction
Authors: Beasley Gary S. , Nelson-McMillan Kristen , Vricella Luca , Thompson William R. , Ravekes William
Published: January 2018

Mechanical circulatory support options remain limited for pediatric patients, especially neonates. The only U.S. Food and Drug Administration-approved pediatric device remains the Berlin Heart EXCOR, which unfortunately carries with it a 20–30% risk of neurologic complications, such as strokes. We demonstrate a new technique of direct echocardiographic color-Doppler imaging of the Berlin Heart valves to detect valve regurgitation. Increases in valve regurgitation could indicate issues with pump-valve thrombosis or increased afterload leading to valve insufficiency. Early recognition of valve thrombosis or insufficiency may reduce neurologic complications and lead to timely pump adjustments or replacement.
Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort
Authors: Godat Sébastien , Fournier Nicolas , Safroneeva Ekaterina , Juillerat Pascal , Nydegger Andreas , Straumann Alex , Vavricka Stephan , Biedermann Luc , Greuter Thomas , Fraga Montserrat , Abdelrahman Karim , Hahnloser Dieter , Sauter Bernhard , Rogler Gerhard , Michetti Pierre , Schoepfer Alain M.
Published: January 2018

Background and aim

Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort.

Patients and methods

A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine).

Results

A total of 3192 patients were analyzed, of whom 1792 (56.1%) had Crohn’s disease, 1322 (41.4%) had ulcerative colitis, and 78 (2.5%) had IBD unclassified. Of 3138 patients treated with IBD drugs, 2129 (67.8%) presented with one or several drug-related side effects necessitating drug cessation. We found a significant positive correlation between the number of concomitantly administered IBD drugs and the occurrence of side effects requiring drug cessation (P<0.001). Logistic regression modeling identified Crohn’s disease diagnosis [odds ratio (OR)=1.361, P=0.017], presence of extraintestinal manifestations (OR=2.262, P<0.001), IBD-related surgery (OR=1.419, P=0.006), and the increasing number of concomitantly used IBD drugs [OR=2.007 (P<0.001) for two concomitantly used IBD drugs; OR=3.225 (P<0.001) for at least three concomitantly used IBD drugs] to be associated significantly with the occurrence of IBD drug-related adverse events that necessitated treatment cessation.

Conclusion

Physicians should keep in mind that the number of concomitantly administered IBD drugs is the main risk factor for drug-related adverse events necessitating treatment cessation.
Clarifying the role of C-reactive protein as a bacterial infection predictor in decompensated cirrhosis
Authors: Perdigoto David N. , Figueiredo Pedro N. , Tomé Luís F.
Published: January 2018

Introduction

Bacterial infections are frequent in cirrhosis and may induce other deleterious complications. Ultrasensitive C-reactive protein (US-CRP), like other acute-phase proteins, is often considered useful in predicting bacterial infection in decompensated cirrhosis. However, US-CRP’s reliability remains inconclusive, as inflammation in cirrhosis causes US-CRP synthesis independently of infection. The aim of this study was to clarify US-CRP’s role as an infection predictor in decompensated cirrhosis.

Patients and methods

This was a prospective single-center study with systematic inclusion of cirrhotic patients admitted because of decompensation.

Results

A total of 118 patients were enrolled, of whom 47 (39.8%) had an overt infection, defined by clinical and laboratory/imaging criteria. Within those, 17 had infection confirmed by culture bacterial identification. Escherichia coli was the most frequent isolated bacteria. Seventeen patients had spontaneous bacterial peritonitis, but only four (23.5%) had positive ascitic fluid cultures. US-CRP levels were significantly higher in cases of overt infection and positive culture groups than the no infection group (median: 4.14 and 6.40 vs. 1.11 mg/dl, P<0.0001 for both). When considering both overt infection and positive culture groups, the US-CRP values of area under the curve as an infection predictor were, respectively, 0.824 and 0.870, P<0.0001 for both, with associated cutoff values of 2.40 and 3.92 mg/dl, and sensitivity and specificity of 78.7/74.6 and 82.4/79.2%, respectively.

Conclusion

The ideal US-CRP infection confirmatory cutoff is probably situated between 2.40 and 3.92 mg/dl. However, as infection is somewhat concealed and hazardous in cirrhotic patients, if not considered with lower US-CRP levels according to specific clinic scenarios, it should be carefully considered, at least, if US-CRP is greater than 2.40 mg/dl (0.5 mg/dl normal upper cutoff).
Determinants of self-rated health in older adults before and 3 months after an emergency department visit: a prospective study
Authors: Van Deudekom Floor J. , De Gelder Jelle , Lucke Jacinta A. , Oostendorp – Lange Anneleen , Anten Sander , Blauw Gerard J. , De Groot Bas , Mooijaart Simon P.
Published: January 2018

Objectives

Self-rated health (SRH) is an important patient-reported outcome, but little is known about SRH after a visit to the emergency department (ED). We investigated the determinants of decline in SRH during 3 months after an ED visit in older patients.

Design

This was a multicenter prospective cohort study including acutely presenting older ( ≥ 70 years) patients in the ED (the Netherlands). Patients were asked to self-rate their health between 0 and 10. The main outcome was a decline in SRH defined as a transition of a SRH of at least 6 to a SRH of less than 6, 3 months after the patient’s visit to the ED.

Results

Three months after the ED visit, 870 (71.4%) patients had a stable SRH and 209 (11.5%) patients declined in SRH. Independent predictors with a decline in SRH were: male gender (OR 1.83) living alone (OR 1.56), living in residential care or nursing home (OR 2.75), number of different medications (OR 1.08), using a walking device (OR 1.70), and the Katz-ADL score (OR 1.22). Patients with functional decline 3 months after an ED visit show a steeper decline in the mean SRH (0.68 points) than patients with no functional decline (0.12 points, P < 0.001).

Conclusion

Decline in SRH after an ED visit in older patients is at least partly dependent on factors of functional capacity and functional decline. Preventive interventions to maintain functional status may be the solution to maintain SRH, but more research is needed to further improve and firmly establish the clinical usability of these findings.
Emergency general surgery in geriatric patients: A statewide analysis of surgeon and hospital volume with outcomes
Authors: Mehta Ambar , Dultz Linda A. , Joseph Bellal , Canner Joseph K. , Stevens Kent , Jones Christian , Haut Elliott R. , Efron David T. , Sakran Joseph V.
Published: January 2018

BACKGROUND

Geriatric patients undergoing emergency general surgery (EGS) face significant morbidity and mortality. We assessed how surgeon and hospital volumes affected these outcomes.

METHODS

We identified patients at least 65 years old in Maryland’s Health Services Cost Review Commission database from 2012 to 2014 who underwent one of 12 EGS procedures, as defined by the American Association for the Surgery of Trauma, and then calculated four outcomes: mortality rate, the incidence of at least one of eight common in-hospital EGS complications, failure-to-rescue (death after experiencing a postoperative complication), and the 30-day readmission rate. Median annual volumes of geriatric-EGS procedures divided both surgeons and hospitals into two groups (low volume and high volume). Multivariable logistic regressions calculated associations between the volume groups and outcomes after adjusting for patient, surgeon, and hospital factors, and hospital clusters.

RESULTS

We identified 3,832 patients who had an EGS procedure by 302 surgeons (median: 8 geriatric-EGS/year, IQR: 3–18) at 44 hospitals (median: 82 geriatric-EGS/year, IQR: 35–132). While operating on 16.5% of all geriatric-EGS patients, low-volume surgeons had higher risk-adjusted adverse outcomes: mortality (7.0% vs. 4.0%, p = 0.005), in-hospital complications (22.1% vs. 19.7%, p = 0.13), failure-to-rescue (17.3% vs. 12.1%, p = 0.021), and 30-day readmissions (11.2% vs. 10.0%, p = 0.55). After adjustment, low-volume surgeons were associated with higher mortality (adjusted odds ratio [aOR] 1.86, 95% CI [1.21–2.86]) and failure-to-rescue rates (aOR 1.74 [1.09–2.80]) but not in-hospital complications (aOR 1.20 [0.95–1.51]) or 30-day readmissions (aOR 1.07 [0.85–1.34]). In contrast, low-volume hospitals relative to high-volume hospitals, and hospitals serving lower proportions of geriatric-EGS patients, were not associated with adverse outcomes.

CONCLUSION

Relative to their higher-volume counterparts, surgeons performing eight or fewer geriatric-EGS procedures annually were associated with an 86% higher odds of death and 74% higher odds of failure-to-rescue in this elderly EGS patient population. These findings underscore the need for focused care of elderly surgical patients.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level IV.
Tranexamic Acid: Promise or Panacea
Authors: Cornelius Brian G. , McCarty Karen , Hylan Kristi , Cornelius Angela , Carter Keith , Smith Kenneth W. G. , Ristic Srdan , Vining Daniel , Cvek Urska , Trutschl Marjan
Published: January 2018

The MATTERs and CRASH-2 studies demonstrate that tranexamic acid (TXA) reduces mortality in patients with traumatic hemorrhage. However, their results, conducted in foreign countries and with U.S. military soldiers, provoke concerns over generalizability to civilian trauma patients in the United States was reported. The evaluation of patient outcomes following treatment with TXA by a civilian air medical program. A retrospective chart review of trauma patients transported by air service to a Level 1 trauma center was conducted. For the purposes of intervention evaluation, patients meeting this criterion for the 2 years (2012–2014) prior to therapy implementation were compared with patients treated during the 2-year study period (2014–2016). Goals were to evaluate morbidity, mortality, and length of stay. During the review, 82 control and 49 study patients were identified as meeting inclusion criteria. Patients in the control group were found to be less acute, which correlated with shorter hospital stays and better discharge outcomes. Multiple patients in the study group who should have expired according to a significantly elevated Trauma Revised Injury Severity Score (TRISS) survived, whereas multiple patients in the control group expired despite a low TRISS calculation. This is the first outcome-based study conducted in a U.S. trauma system. The outcomes in civilian trauma patients in the United States do not follow that of the previous MATTERs and CRASH-2 studies. However, this study still shows benefit to TXA administration and reduced risk for administration to patients with head trauma and occurrence of venous thromboembolism. Randomized control trials are needed to evaluate the role of TXA administration in the United States.
What the Advanced Practice Nurse in the Emergency Department Needs to Know About the Health Risks and Hazards of Electronic Cigarette Use by Youth
Authors: Simerson Darlie
Published: January 2018

Despite the decline in traditional tobacco use among teens and young adults, the rapid increase in electronic cigarette (EC) use has filled the gap, raising concern that this will usher in a new generation of tobacco users. Although long-term effects have not been clearly established, EC use is not without risks or hazards that may be encountered by the advanced practice nurse in the emergency department (ED). The ED presents an opportune moment for health promotion and risk reduction education for patients and families, but there are also dangers to EC use that the practitioner should be aware of and prepared to manage. Nicotine, found in most EC liquids, is well known to be a neurotoxin that affects brain development in young people. It is important to inform young people and families that EC products may contain not only nicotine but also other harmful chemicals and are not just harmless water vapor. Other toxins found in EC liquids and vapors raise questions about the health impact of long-term EC use and add additional concerns for secondhand exposure for children and pregnant women. The EC is also used by youth to inhale concentrated forms of cannabis, which could be a precursor to EC use for other illicit drugs. Hazards to be prepared for in the ED are accidental ingestion of EC liquids by children and intentional overdose of concentrated liquids. Severe injuries have been reported from explosions of EC devices as well. The ED is a starting point for EC screening and education of young people and families. Advanced practice nurses must also anticipate and be prepared to handle any other untoward effects from exposures to devices and liquids. The purpose of this article is to inform and prepare advanced practice nurses with the latest information to manage these patient encounters.
Decreased Cognitive Functioning After Electroconvulsive Therapy Is Related to Increased Hippocampal Volume
Authors: van Oostrom Iris , van Eijndhoven Philip , Butterbrod Elke , van Beek Maria H. , Janzing Joost , Donders Rogier , Schene Aart , Tendolkar Indira
Published: January 2018

Objective

Electroconvulsive therapy (ECT) is still the most effective treatment of severe and therapy-refractory major depressive disorder. Cognitive side effects are the major disadvantage of ECT. Cognitive deficits are generally temporary in nature and may be mediated by the hippocampus. Recent studies have shown a temporary increase in hippocampal volume and a temporary decrease in cognitive functioning post-ECT compared with pre-ECT. This study investigates whether these volumetric changes are related to changes in cognitive functioning after ECT.

Methods

Nineteen medication-free patients with treatment-resistant major depressive disorder underwent a whole-brain magnetic resonance imaging scan and a neuropsychological examination (including the Rey auditory verbal learning task, Wechsler Memory Scale Visual Reproduction, fluency, Trail Making Task) within 1 week before and within 1 week after the course of ECT. Electroconvulsive therapy was administered twice a week bitemporally with a brief pulse. A matched healthy control group (n = 18) received the same neuropsychological examination and at a similar interval to that of the patients.

Results

Hippocampal volumes increased significantly from pretreatment to posttreatment in patients. Mean performance on cognitive tasks declined, or remained stable, whereas performance in controls generally improved because of retesting effects. The increase in hippocampal volume was related to changes in cognitive performance, indicating that this increase co-occurred with a decrease in cognitive functioning.

Conclusions

Our findings tentatively suggest that the temporal increase in hippocampal volume after treatment, which may result from neurotrophic processes and is thought to be crucial for the antidepressive effect, is also related to the temporary cognitive side effects of ECT.
Efficient analysis of stochastic gene dynamics in the non-adiabatic regime using piecewise deterministic Markov processes
Authors: Lin Yen Ting , Buchler Nicolas E.
Published: January 2018

Single-cell experiments show that gene expression is stochastic and bursty, a feature that can emerge from slow switching between promoter states with different activities. In addition to slow chromatin and/or DNA looping dynamics, one source of long-lived promoter states is the slow binding and unbinding kinetics of transcription factors to promoters, i.e. the non-adiabatic binding regime. Here, we introduce a simple analytical framework, known as a piecewise deterministic Markov process (PDMP), that accurately describes the stochastic dynamics of gene expression in the non-adiabatic regime. We illustrate the utility of the PDMP on a non-trivial dynamical system by analysing the properties of a titration-based oscillator in the non-adiabatic limit. We first show how to transform the underlying chemical master equation into a PDMP where the slow transitions between promoter states are stochastic, but whose rates depend upon the faster deterministic dynamics of the transcription factors regulated by these promoters. We show that the PDMP accurately describes the observed periods of stochastic cycles in activator and repressor-based titration oscillators. We then generalize our PDMP analysis to more complicated versions of titration-based oscillators to explain how multiple binding sites lengthen the period and improve coherence. Last, we show how noise-induced oscillation previously observed in a titration-based oscillator arises from non-adiabatic and discrete binding events at the promoter site.
Hydrodynamics govern the pre-fusion docking time of synaptic vesicles
Authors: Singh Pankaj , Hui Chung-Yuen
Published: January 2018

Synaptic vesicle fusion is a crucial step in the neurotransmission process. Neurotransmitter-filled vesicles are pre-docked at the synapse by the mediation of ribbon structures and SNARE proteins at the ribbon synapses. An electrical impulse triggers the fusion process of pre-docked vesicles, leading to the formation of a fusion pore and subsequently resulting in the release of neurotransmitter into the synaptic cleft. In this study, a continuum model of lipid membrane along with lubrication theory is used to determine the traverse time of the synaptic vesicle under the influence of hydrodynamic forces. We find that the traverse time is strongly dependent on how fast the driving force decays or grows with closure of the gap between the vesicle and the plasma membrane. If the correct behaviour is chosen, the traverse time obtained is of the order of a few hundred milliseconds and lies within the experimentally obtained value of approximately 250 ms (Zenisek D, Steyer JA, Almers W. 2000Nature406, 849–854 (doi:10.1038/35022500)). We hypothesize that there are two different force behaviours, which complies with the experimental findings of pre-fusion docking of synaptic vesicles at the ribbon synapses. The common theme in the proposed force models is that the driving force has to very rapidly increase or decrease with the amount of clamping.
The
Pseudomonas aeruginosa
ExoY phenotype of high-copy-number recombinants is not detectable in natural isolates
Authors: Munder Antje , Rothschuh Justin , Schirmer Bastian , Klockgether Jens , Kaever Volkhard , Tümmler Burkhard , Seifert Roland , Kloth Christina
Published: January 2018

The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of
Pseudomonas aeruginosa
. We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103Δ
exoUexoT::Tc
pUCP
exoY
, its vector control strain PA103Δ
exoUexoT::Tc
pUCP18, its loss-of-function control PA103Δ
exoUexoT::Tc
pUCP
exoY
K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the
P. aeruginosa
carrier of the
exoY-
plasmid produced high levels of cUMP and caused the most severe course of infection. The pathology ascribed to ExoY from studies using the high-copy-number plasmid on mammalian cells
in vitro
and
in vivo
was not observed with natural
P. aeruginosa
isolates. This indicates that the role of ExoY during infection with real-life
P. aeruginosa
still needs to be resolved.
From conservation genetics to conservation genomics: a genome-wide assessment of blue whales (Balaenoptera musculus) in Australian feeding aggregations
Authors: Attard Catherine R. M. , Beheregaray Luciano B. , Sandoval-Castillo Jonathan , Jenner K. Curt S. , Gill Peter C. , Jenner Micheline-Nicole M. , Morrice Margaret G. , Möller Luciana M.
Published: January 2018

Genetic datasets of tens of markers have been superseded through next-generation sequencing technology with genome-wide datasets of thousands of markers. Genomic datasets improve our power to detect low population structure and identify adaptive divergence. The increased population-level knowledge can inform the conservation management of endangered species, such as the blue whale (Balaenoptera musculus). In Australia, there are two known feeding aggregations of the pygmy blue whale (B. m. brevicauda) which have shown no evidence of genetic structure based on a small dataset of 10 microsatellites and mtDNA. Here, we develop and implement a high-resolution dataset of 8294 genome-wide filtered single nucleotide polymorphisms, the first of its kind for blue whales. We use these data to assess whether the Australian feeding aggregations constitute one population and to test for the first time whether there is adaptive divergence between the feeding aggregations. We found no evidence of neutral population structure and negligible evidence of adaptive divergence. We propose that individuals likely travel widely between feeding areas and to breeding areas, which would require them to be adapted to a wide range of environmental conditions. This has important implications for their conservation as this blue whale population is likely vulnerable to a range of anthropogenic threats both off Australia and elsewhere.
A novel adenine-based metal organic framework derived nitrogen-doped nanoporous carbon for flexible solid-state supercapacitor
Authors: Li Haowen , Fu Dongying , Zhang Xian-Ming
Published: January 2018

In this article, we have synthesized a series of nitrogen-doped nanoporous carbon (NPC) from metal organic framework of UiO-66 with different ratios of adenine and 1,4-benzendicarboxylate (H
2
BDC) coated on carbon nanotube film (CNTF) to obtain a flexible porous electrode (NPC/CNTF). It is worth noting that the introduction of adenine at different ratios did not change the structure of UiO-66. We also investigated the effect of carbonization temperature from 800 to 1000°C on the electrochemical properties of the NPC. The ratio (H
2
BDC:adenine) 9 : 1 and the NPC carbonized at 900°C (denoted as NPC-1-900) exhibits better electrochemical properties. The results show that NPC-1-900/CNTF electrode exhibits an exceptional areal capacitance of 121.5 mF cm
−2
compared to that of PC-900/CNTF electrode (22.8 mF cm
−2
) at 5 mV s
−1
in a three-electrode system, indicating that the incorporation of nitrogen is beneficial to the electrochemical properties of nanoporous carbon. A symmetric flexible solid-state supercapacitor of NPC-1-900/CNTF has also been assembled and tested. Electrochemical data show that the device exhibited superior areal capacitance (43.2 mF cm
−2
) at the scan rate of 5 mV s
−1
; the volumetric energy density is 57.3 µWh cm
−3
and the volumetric power density is 2.4 mW cm
−3
at the current density of 0.5 mA cm
−2
based on poly(vinyl alcohol)/H
3
PO
4
gel electrolyte. For practical application, we have also studied the bending tests of the device, which show that the device exhibits outstanding mechanical stability under different bending angles. Furthermore, the flexible device shows excellent cyclic stability, which can retain 91.5% of the initial capacitance after 2000 cycles.
Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents
Authors: Marassi Valentina , Di Cristo Luisana , Smith Stephen G. J. , Ortelli Simona , Blosi Magda , Costa Anna L. , Reschiglian Pierluigi , Volkov Yuri , Prina-Mello Adriele
Published: January 2018

Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a ‘purpose-specific active applicability window’ to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response
in vitro
have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic
Escherichia coli
. The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety.
A new stem group echinoid from the Triassic of China leads to a revised macroevolutionary history of echinoids during the end-Permian mass extinction
Authors: Thompson Jeffrey R. , Hu Shi-xue , Zhang Qi-Yue , Petsios Elizabeth , Cotton Laura J. , Huang Jin-Yuan , Zhou Chang-yong , Wen Wen , Bottjer David J.
Published: January 2018

The Permian–Triassic bottleneck has long been thought to have drastically altered the course of echinoid evolution, with the extinction of the entire echinoid stem group having taken place during the end-Permian mass extinction. The Early Triassic fossil record of echinoids is, however, sparse, and new fossils are paving the way for a revised interpretation of the evolutionary history of echinoids during the Permian–Triassic crisis and Early Mesozoic. A new species of echinoid,
Yunnanechinus luopingensis
n. sp. recovered from the Middle Triassic (Anisian) Luoping Biota fossil Lagerstätte of South China, displays morphologies that are not characteristic of the echinoid crown group. We have used phylogenetic analyses to further demonstrate that
Yunnanechinus
is not a member of the echinoid crown group. Thus a clade of stem group echinoids survived into the Middle Triassic, enduring the global crisis that characterized the end-Permian and Early Triassic. Therefore, stem group echinoids did not go extinct during the Palaeozoic, as previously thought, and appear to have coexisted with the echinoid crown group for at least 23 million years. Stem group echinoids thus exhibited the Lazarus effect during the latest Permian and Early Triassic, while crown group echinoids did not.
Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways
Authors: Jansen Philip R. , Watanabe Kyoko , Stringer Sven , Skene Nathan , Bryois Julien , Hammerschlag Anke R. , de Leeuw Christiaan A. , Benjamins Jeroen , Muñoz-Manchado Ana B. , Nagel Mats , Savage Jeanne E. , Tiemeier Henning , White Tonya ,   The 23andMe Research Team, Tung Joyce Y. , Hinds David A. , Vacic Vladimir , Sullivan Patrick F. , van der Sluis Sophie , Polderman Tinca J.C. , Smit August B. , Hjerling-Leffler Jens , Van Someren Eus J.W. , Posthuma Danielle
Published: January 2018

Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia complaints. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.