bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell network analysis with a mixture of Nested Effects Models
Authors: Pirkl Martin , Beerenwinkel Niko
Published: July 2018

Motivation

New technologies allow for the elaborate measurement of different traits of single cells under genetic perturbations. These interventional data promise to elucidate intra-cellular networks in unprecedented detail and further help to improve treatment of diseases like cancer. However, cell populations can be very heterogeneous.

Results

We developed a mixture of Nested Effects Models (M&NEM) for single-cell data to simultaneously identify different cellular subpopulations and their corresponding causal networks to explain the heterogeneity in a cell population. For inference, we assign each cell to a network with a certain probability and iteratively update the optimal networks and cell probabilities in an Expectation Maximization scheme. We validate our method in the controlled setting of a simulation study and apply it to three data sets of pooled CRISPR screens generated previously by two novel experimental techniques, namely Crop-Seq and Perturb-Seq.

Availability and implementation

The mixture Nested Effects Model (M&NEM) is available as the R-package mnem at https://github.com/cbg-ethz/mnem/.

Supplementary information

Supplementary data are available at Bioinformatics online.
RNAvista: a webserver to assess RNA secondary structures with non-canonical base pairs
Authors: Antczak Maciej , Zablocki Marcin , Zok Tomasz , Rybarczyk Agnieszka , Blazewicz Jacek , Szachniuk Marta
Published: July 2018

Motivation

In the study of 3D RNA structure, information about non-canonical interactions between nucleobases is increasingly important. Specialized databases support investigation of this issue based on experimental data, and several programs can annotate non-canonical base pairs in the RNA 3D structure. However, predicting the extended RNA secondary structure which describes both canonical and non-canonical interactions remains difficult.

Results

Here, we present RNAvista that allows predicting an extended RNA secondary structure from sequence or from the list enumerating canonical base pairs only. RNAvista is implemented as a publicly available webserver with user-friendly interface. It runs on all major web browsers.

Availability and implementation

http://rnavista.cs.put.poznan.pl
Kmer-db: instant evolutionary distance estimation
Authors: Deorowicz Sebastian , Gudyś Adam , Długosz Maciej , Kokot Marek , Danek Agnieszka
Published: July 2018

Kmer-db is a new tool for estimating evolutionary relationship on the basis of k-mers extracted from genomes or sequencing reads. Thanks to an efficient data structure and parallel implementation, our software estimates distances between 40 715 pathogens in <7 min (on a modern workstation), 26 times faster than Mash, its main competitor.

Availability and implementation

https://github.com/refresh-bio/kmer-db and http://sun.aei.polsl.pl/REFRESH/kmer-db.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus
Authors: Newton Paul N , Keolouangkhot Valy , Lee Sue J , Choumlivong Khamla , Sisouphone Siho , Choumlivong Khamloune , Vongsouvath Manivanh , Mayxay Mayfong , Chansamouth Vilada , Davong Viengmon , Phommasone Koukeo , Sirisouk Joy , Blacksell Stuart D , Nawtaisong Pruksa , Moore Catrin E , Castonguay-Vanier Josée , Dittrich Sabine , Rattanavong Sayaphet , Chang Ko , Darasavath Chirapha , Rattanavong Oudayvone , Paris Daniel H , Phetsouvanh Rattanaphone
Published: July 2018

Background

Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.

Methods

A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.

Results

Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.

Conclusion

In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.

Clinical Trial Registration

ISRCTN47812566.
Optimal error estimates of the unilateral contact problem in a curved and smooth boundary domain by the penalty method
Authors: Dione Ibrahima
Published: July 2018

We consider linear finite elements to approximate the elasticity equations with unilateral contact boundary conditions, in a bounded two- or three-dimensional domain with curved and smooth boundary. We use the penalty method to weakly impose these boundary conditions. We establish an error estimate in the energy norm with respect to the mesh size $h$ and the penalty parameter $\varepsilon $. Assuming $\boldsymbol{H}^{\frac{3}{2}+\nu }\left (\varOmega \right )$ regularity of the solution, $0 < \nu \leq \frac{1}{2}$, we obtain an $\mathcal{O}\,(h^{\frac{1}{2}+\nu } + \varepsilon ^{\frac{1}{2}+\nu })$ convergence rate. Therefore, if the penalty parameter is chosen as $\varepsilon (h) := ch^{\theta }$ with $0 < \theta \leq 1$, we obtain an $\mathcal{O}\,(h^{\theta (\frac{1}{2}+\nu )})$ convergence rate. Thus, the optimal linear convergence rate is obtained when $\varepsilon $ behaves like $h$ (that is, $\theta = 1$) and $\nu = \frac{1}{2}$. We present a numerical example to illustrate the theoretical analysis.
Frobenius Splitting of Thick Flag Manifolds of Kac–Moody Algebras
Authors: Kato Syu
Published: July 2018

We explain that the Plücker relations provide the defining equations of the thick flag manifold associated to a Kac–Moody algebra. This naturally transplants the result of Kumar–Mathieu–Schwede about the Frobenius splitting of thin flag varieties to the thick case. As a consequence, we provide a description of the space of global sections of a line bundle of a thick Schubert variety as conjectured in Kashiwara–Shimozono [13]. This also yields the existence of a compatible basis of thick Demazure modules and the projective normality of the thick Schubert varieties.
US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011–2015
Authors: Lovegrove Maribeth C , Geller Andrew I , Fleming-Dutra Katherine E , Shehab Nadine , Sapiano Mathew R P , Budnitz Daniel S
Published: July 2018

Background

Antibiotics are among the most commonly prescribed medications for children; however, at least one-third of pediatric antibiotic prescriptions are unnecessary. National data on short-term antibiotic-related harms could inform efforts to reduce overprescribing and to supplement interventions that focus on the long-term benefits of reducing antibiotic resistance.

Methods

Frequencies and rates of emergency department (ED) visits for antibiotic adverse drug events (ADEs) in children were estimated using adverse event data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project and retail pharmacy dispensing data from QuintilesIMS (2011–2015).

Results

On the basis of 6542 surveillance cases, an estimated 69464 ED visits (95% confidence interval, 53488–85441) were made annually for antibiotic ADEs among children aged ≤19 years from 2011 to 2015, which accounts for 46.2% of ED visits for ADEs that results from systemic medication. Two-fifths (40.7%) of ED visits for antibiotic ADEs involved a child aged ≤2 years, and 86.1% involved an allergic reaction. Amoxicillin was the most commonly implicated antibiotic among children aged ≤9 years. When we accounted for dispensed prescriptions, the rates of ED visits for antibiotic ADEs declined with increasing age for all antibiotics except sulfamethoxazole-trimethoprim. Amoxicillin had the highest rate of ED visits for antibiotic ADEs among children aged ≤2 years, whereas sulfamethoxazole-trimethoprim resulted in the highest rate among children aged 10 to 19 years (29.9 and 24.2 ED visits per 10000 dispensed prescriptions, respectively).

Conclusions

Antibiotic ADEs lead to many ED visits, particularly among young children. Communicating the risks of antibiotic ADEs could help reduce unnecessary prescribing. Prevention efforts could target pediatric patients who are at the greatest risk of harm.
Goodness-Fixing Isn’t Good Enough: A Reply to McHugh and Way
Authors: Hlobil Ulf
Published: July 2018

According to McHugh and Way, reasoning is a person-level attitude revision that is regulated by its constitutive aim of getting fitting attitudes. They claim that this account offers an explanation of what is wrong with reasoning in ways one believes to be bad, and that this explanation is an alternative to an explanation that appeals to the so-called Taking Condition. I argue that their explanation is unsatisfying.
Trends in social inequality in loneliness among adolescents 1991–2014
Authors: Madsen K R , Holstein B E , Damsgaard M T , Rayce S B , Jespersen L N , Due P
Published: July 2018

Background

Loneliness and social inequality in health are important public health concerns. We examined (i) trends in loneliness among adolescents from 1991 to 2014 in Denmark and (ii) trends in social inequality in loneliness.

Methods

Study population: 11–15-year olds in random samples of schools in 1991, 1994, 1998, 2006 and 2014, n = 19 096. Loneliness was measured by a single item and social background by parents’ occupational social class (OSC). We calculated absolute (%) differences in loneliness between high and low OSC and relative differences by odds ratio for loneliness.

Results

Across all surveys, 6.3% reported feeling lonely. The prevalence increased from 4.4% in 1991 to 7.2% in 2014. The prevalence of loneliness in high, middle and low OSC was 5.8, 5.9 and 8.0%. The increase in loneliness was more pronounced in higher than lower OSC, resulting in a decreasing absolute social inequality in loneliness. The statistical interaction between OSC and survey year was significant, P = 0.0176, i.e. the relative social inequality in loneliness also decreased from 1991 to 2014.

Conclusion

The prevalence of loneliness increased from 1991 to 2014. The social inequality in loneliness decreased in both absolute and relative terms because of a rising prevalence of loneliness among children from high OSC.
Characteristics of sleep-active neurons in the medullary parafacial zone in rats
Authors: Alam Md Aftab , Kostin Andrey , Siegel Jerome , McGinty Dennis , Szymusiak Ronald , Alam Md Noor
Published: July 2018

Growing evidence supports a role for the medullary parafacial zone in non-rapid eye movement (non-REM) sleep regulation. Cell-body specific lesions of the parafacial zone or disruption of its GABAergic/glycinergic transmission causes suppression of non-REM sleep, whereas, targeted activation of parafacial GABAergic/glycinergic neurons reduce sleep latency and increase non-REM sleep amount, bout duration, and cortical electroencephalogram (EEG) slow-wave activity. Parafacial GABAergic/glycinergic neurons also express sleep-associated c-fos immunoreactivity. Currently, it is not clear if parafacial neurons are non-REM sleep-active and/or REM sleep-active or play a role in the initiation or maintenance of non-REM sleep. We recorded extracellular discharge activity of parafacial neurons across the spontaneous sleep-waking cycle using microwire technique in freely behaving rats. Waking-, non-REM sleep-, and REM sleep-active neuronal groups were segregated by the ratios of their discharge rate changes during non-REM and REM sleep versus waking and non-REM sleep versus REM sleep. Parafacial neurons exhibited heterogeneity in sleep-waking discharge patterns, but 34 of 86 (40%) recorded neurons exhibited increased discharge rate during non-REM sleep compared to waking. These neurons also exhibited increased discharge prior to non-REM sleep onset, similar to median preoptic nucleus (MnPO) and ventrolateral preoptic area (VLPO) sleep-active neurons. However, unlike MnPO and VLPO sleep-active neurons, parafacial neurons were weakly-moderately sleep-active and exhibited a stable rather than decreasing discharge across sustained non-REM sleep episode. We show for the first time that the medullary parafacial zone contains non-REM sleep-active neurons. These neurons are likely functionally important brainstem compliments to the preoptic-hypothalamic sleep-promoting neuronal networks that underlie sleep onset and maintenance.
Managing sexually transmitted infections
Authors: Johnson-Mallard Versie , Curry Kim , Chandler Rasheeta , Alexander Ivy , Kostas-Polston Elizabeth , Orsega Susan , Woods Nancy Fugate
Published: July 2018

Guidelines for the prevention and management of sexually transmitted infections (STIs) are updated periodically while new science is continuously developed. Advanced practice registered nurses implement clinical decisions based on current guidelines and evidence. This article provides recent updates on managing STIs.
Preoperative Planning for Percutaneous Transsacral, Transiliac Screws
Authors: Blum Laura E. , Hake Mark E.
Published: July 2018

Percutaneous transsacral, transiliac screw placement is a well-described, well-established management option for unstable posterior pelvic ring injuries. Safe and effective placement of these screws relies on extensive preoperative planning and scrutiny of the preoperative images. Malpositioning of the implants risks injury to the surrounding neurovascular structures. We present our methods for preoperative templating for safe placement of transsacral, transiliac screws.
Lateral Distal Femur Plate for Periprosthetic Fracture
Authors: Yarboro Seth R.
Published: July 2018

In this case, a lateral locking plate is used for fixation of a periprosthetic distal femur fracture in a 68-year-old woman. Modern implants with locking screw options and soft-tissue–sparing surgical techniques have improved the care of periprosthetic distal femur fractures. Although much debate about the working length and technical variables of plating exists, it is generally accepted that longer (>10 hole) plates with adequate working length and careful soft-tissue handling are preferred. This case outlines a stepwise approach to distal femur fractures to achieve appropriate plate position and restoration of alignment while avoiding excessive surgical exposure or soft-tissue dissection. In this case, retrograde intramedullary nail was not considered because of the distal nature of the fracture, but this option may be favorable for cruciate-retaining total knee arthroplasty or open box designs that will accommodate nail insertion. Although weight bearing was protected for 6 weeks, plate fixation allows early rehabilitation and knee range of motion. This patient went on to successful union and excellent clinical outcome with return to baseline function.
Surgical Technique: Achieving Anatomic Alignment With Temporizing, Ankle-Spanning External Fixation
Authors: Liskutin Tomas , Bernstein Mitchell , Summers Hobie , Lack William
Published: July 2018

Introduction:

Severe injuries to the ankle frequently result in soft tissue trauma too severe to proceed with immediate definitive fixation. Additionally, patients with multiple or vascular injuries may need a temporizing measure before undergoing definitive treatment. Temporizing, ankle-spanning external fixation offers a management strategy that allows for soft tissue rest and prioritized treatment of patients with polytrauma.

Methods:

The video demonstrates 2 clinical cases managed with temporizing, ankle-spanning external fixation: a pilon fracture and a bimalleolar ankle fracture–dislocation.

Results:

The indications, advantages, and a systematic operative approach to applying ankle-spanning external fixation are presented. Specific attention is paid to restoring an anatomic alignment of the ankle.

Conclusions:

Temporizing, ankle-spanning external fixation is an important modality in the management of fractures about the ankle, especially in patients with dislocation and/or severe soft tissue injury. A systematic approach that initially addresses length, followed by sagittal and coronal plane correction, can be used to restore anatomic alignment of the ankle.
Surgical Technique: Anterolateral Approach to the Humerus
Authors: Liskutin Tomas , Summers Hobie , Lack William , Bernstein Mitchell
Published: July 2018

Introduction:

Although most humeral shaft fractures can be treated nonoperatively, many patients do benefit significantly from surgical treatment. The anterolateral approach to the humerus provides excellent exposure to the humeral shaft, especially to more proximal aspects. In addition, the approach can be extended both proximally and distally, providing the surgeon a dynamic exposure to the humerus for the treatment of fractures and other pathologies.

Methods:

This video highlights a clinical case where a mid-shaft humerus fracture was diagnosed and treated with open reduction internal fixation using an 8-hole 4.5-mm limited contact dynamic compression plate through an anterolateral approach.

Results:

We present indications, anatomic considerations, and surgical techniques used to surgically treat a transverse, mid-shaft humerus fracture through an anterolateral approach. In addition, we demonstrate the use of a push–pull screw to aid in achieving appropriate compression across a fracture site. Using this technique, an anatomic reduction and satisfactory clinical outcome were achieved.

Conclusions:

The anterolateral approach to the humerus offers excellent exposure to some humeral shaft fractures, particularly those that lie more proximally. However, its use must be weighed carefully against several other approach options, and the surgeon must account for the specific fracture pattern, as well as their own comfort and familiarity with the approach.
Posterior Scapula Approaches: Extensile and Modified Judet
Authors: Cole Peter A. , Dugarte Anthony J.
Published: July 2018

The Extensile Judet has been widely used in the management of scapula fractures. An enhanced understanding of these injuries, however, has allowed for the strategic development of alternative methods in which soft tissues may be better spared. The purpose of this video is to highlight the indications and techniques for 2 posterior approaches to the scapula: The Extensile Judet and the Modified Judet. Case 1 demonstrates the Modified Judet approach. The “boomerang” incision follows the curve of the scapula spine and vertebral border, and fixation occurs through an intermuscular window. Case 2 illustrates the Extensile Judet. The incision is identical to that of the Modified Judet, but differs in that posterior musculature is elevated in 1 periosteocutaneous flap. The utility of 2 different posterior approaches to the scapula are described. Both include the same incision, but differ with regards to management of the musculature overlying the fracture. The Modified Judet lacks the exposure of the Extensile approach, but significant soft-tissue trauma is avoided. Regarding the Extensile Judet, substantial tissue trauma is incurred to gain the exposure necessary for complex fracture patterns. Reduction goals, wound closure, and postoperative care remain the same for both approaches. Both approaches are valuable in terms of operative management of scapula fractures, although certain populations may benefit from tissue-sparing procedures.
Supra-acetabular Pelvic External Fixator, Percutaneous With Fluoroscopic Guidance
Authors: Grannis Kimberly , Tidwell John , Cho Rosa
Published: July 2018

Unstable pelvic fractures are associated with high-energy trauma and can lead to increased morbidity and mortality if not managed properly in the acute setting. Early recognition and intervention is crucial for optimal patient outcomes. This article, in addition to the video footage, outlines a safe and effective method for stabilizing unstable pelvic fractures by applying a supra-acetabular pelvic external fixator using fluoroscopic guidance.
Distal Clavicle Fractures: Open Reduction and Internal Fixation With a Hook Plate
Authors: Kirsch Jacob M. , Blum Laura , Hake Mark E.
Published: July 2018

Displaced distal clavicle fractures pose unique challenges because of their propensity for instability. In particular, type II fracture patterns are associated with high rates of nonunion with nonoperative management; therefore, surgical fixation is often recommended. Hook plate fixation has demonstrated reliably high rates of osseous union with good functional outcomes. We present our surgical technique and rationale for using a hook plate in the setting of an unstable distal clavicle fracture.
Distal Tibial Intramedullary Nailing Using an Extraarticular, Lateral Parapatellar Approach in the Semiextended Position
Authors: McAndrew Christopher M. , Ricci William M. , Miller Anna N. , Avery Matthew C.
Published: July 2018

Semiextended positioning can improve the surgeon's ability to obtain, maintain, and fluoroscopically evaluate a fracture reduction when performing fixation with an intramedullary nail, especially in fractures at the proximal and distal ends. Furthermore, this position allows for evaluation of instrument placement, including the start point, without moving the fluoroscopic unit into extremes of angulation or compromising the quality of the beam orientation. The intraarticular suprapatellar approach has been described as a soft tissue approach to maintain the leg in a position that would not complicate management of these fractures, especially those in the proximal third of the tibia. A semiextended extraarticular soft tissue approach to the start point was described by Kubiak et al, and the lateral parapatellar version has become commonly used on the Orthopaedic Trauma Service at Washington University in Saint Louis. This video demonstrates advantages of semiextended positioning while performing reduction and intramedullary nail fixation for distal tibia fractures. This lateral parapatellar approach can be performed without specialized instrumentation, results in precise establishment of the start point and completion of the fixation without injury to the knee.
ORIF With Submuscular Plating of an Intercondylar/Supracondylar Distal Femur Fracture
Authors: Varkey Dax , Ostrum Robert F.
Published: July 2018

Fractures of the distal femur with intercondylar extension and comminution are challenging cases and demand a thorough preoperative evaluation and execution of proper surgical technique. Identification of the intra-articular fractures, including coronal fractures of the lateral condyle, is important in planning surgery and emphasizes the need for computerized tomography scans. Recent advances with anatomic, locking plates have made minimally invasive surgery easier, but joint reduction needs to be performed meticulously in an open manner, and restoration of the mechanical alignment through plate fixation is essential for a good clinical outcome. Stable fixation that allows for early range of motion and mobilization are essential for the patient's recovery. This video demonstrates open reduction and internal fixation of a high-energy supracondylar/intercondylar distal femur fracture and emphasizes minimally invasive, biologically friendly techniques.
Hip Power and “Stiff Knee” Gait: A Tool for Identifying Appropriate Candidates for Rectus Transfer
Authors: Moreira Brunno L. , Karakostas Tasos , Dias Luciano S.
Published: July 2018

Background:

Rectus femoris transfer (RFT) is performed in children with cerebral palsy to treat stiff-knee gait. However, the results are variable in part because there is no gold standard to identify appropriate candidates. Hip flexion kinematics and kinetics are important factors in the determination of peak knee flexion during gait. This study aimed to evaluate whether a kinetic preoperative analysis of hip power can be a predictor of RFT outcomes and determine its usability for identifying appropriate candidates for the procedure.

Methods:

Sixteen children with spastic cerebral palsy (20 limbs) GMFCS I/II who underwent RFT for a stiff-knee gait and had preoperative and postoperative 3D gait analyses were retrospectively evaluated. Patient outcomes were classified as “good” or “poor” according to postoperative results. The outcomes were evaluated as a function of (a) 1-parameter criteria—peak hip power (PHP) with a cut-off magnitude≥0.60 W/kg; (b) 2-parameter criteria—PHP (cut-off magnitude≥0.60 W/kg) and the time the PHP occurred during the gait cycle (tPHP), with a cut-off ≤68% of the gait cycle.

Results:

When the 1-parameter criterion was used, 13 limbs met the criterion; of them, 11 had good outcomes. Seven limbs did not meet the criterion; of them, 6 had poor results (P=0.0049). When the 2-parameter criterion was used, 11 limbs met the criteria; all had good results. Nine limbs did not meet the criterion; of them, 8 had poor results (P=0.0002). PHP+tPHP had the same sensitivity as PHP alone (91%) but with higher specificity (100%) for predicting outcomes. The positive predictive value of magnitude PHP+tPHP was 100%, whereas the accuracy index was 95%.

Conclusions:

Preoperative kinetic evaluation of the hip power characteristics from 3D gait analysis appears to be a very important predictor for RFT outcomes and identifying appropriate candidates for the procedure.

Level of Evidence:

Level III—therapeutic retrospective study.
Double Cycling During Mechanical Ventilation: Frequency, Mechanisms, and Physiologic Implications*
Authors: de Haro Candelaria , López-Aguilar Josefina , Magrans Rudys , Montanya Jaume , Fernández-Gonzalo Sol , Turon Marc , Gomà Gemma , Chacón Encarna , Albaiceta Guillermo M. , Fernández Rafael , Subirà Carles , Lucangelo Umberto , Murias Gastón , Rué Montserrat , Kacmarek Robert M. , Blanch Lluís
Published: July 2018

Objectives:

Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients.

Design:

Prospective, observational study.

Setting:

Three general ICUs in Spain.

Patients:

Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours.

Interventions:

None.

Measurements and Main Results:

We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34–0.87) than in volume control-continuous mandatory ventilation with constant flow 0.27 (0.19–0.38) or volume control-continuous mandatory ventilation with decelerated flow 0.11 (0.06–0.20). Tidal volume in double-cycled breaths was higher in volume control-continuous mandatory ventilation with constant flow and volume control-continuous mandatory ventilation with decelerated flow than in pressure control-continuous mandatory ventilation. Double-cycled breaths were patient triggered in 65.4% and reverse triggered (diaphragmatic contraction stimulated by a previous passive ventilator breath) in 34.6% of cases; the difference was largest in volume control-continuous mandatory ventilation with decelerated flow (80.7% patient triggered and 19.3% reverse triggered). Peak pressure of the second stacked breath was highest in volume control-continuous mandatory ventilation with constant flow regardless of trigger type. Various physiologic factors, none mutually exclusive, were associated with double cycling.

Conclusions:

Double cycling is uncommon but occurs in all patients. Periods without double cycling alternate with periods with clusters of double cycling. The volume of the stacked breaths can double the set tidal volume in volume control-continuous mandatory ventilation with constant flow. Gas delivery must be tailored to neuroventilatory demand because interdependent ventilator setting–related physiologic factors can contribute to double cycling. One third of double-cycled breaths were reverse triggered, suggesting that repeated respiratory muscle activation after time-initiated ventilator breaths occurs more often than expected.
Evaluating a Blended Online Learning Model Among Undergraduate Nursing Students
Authors: Ota Marianne , Peck Blake , Porter Joanne
Published: July 2018

In Australia, the emerging use of technology in higher education has brought about significant change in the delivery of undergraduate nursing programs. Universities are now tasked with delivering a blend of online and face-to-face education, while students face new and sometimes challenging online learning environments with little technical support. This article explores the attitudes held by Bachelor of Nursing students toward the blended educational mode at a rural university in Victoria, Australia. A total of 109 participants constituted a convenience sample from a Bachelor of Nursing program across all 3-year levels. Responses provided by participants who completed an online self-report questionnaire were analyzed via descriptive and inferential statistics. The results indicated that participants struggled with inaccurate expectations of workload and the technical difficulties presented by online modules. Although this area requires further research, to an extent autonomy and flexibility were identified as two prominent traits exhibited by students who flourished in the blended modes. All in all, the results of this study strongly reflect the challenges faced by undergraduate nursing students navigating newly introduced online systems in a blended mode of study.
Severe skin toxicity with organ damage under the combination of targeted therapy following immunotherapy in metastatic melanoma
Authors: Lamiaux Marie , Scalbert Camille , Lepesant Pauline , Desmedt Eve , Templier Carole , Dziwniel Véronique , Staumont-Sallé Delphine , Mortier Laurent
Published: July 2018

Targeted therapy combination (TTC: antiRAF+antiMEK) is known to improve metastatic melanoma survival. Few severe skin toxicities (grade ≥3) are described with first-line TTC (17% for vemurafenib+cobimetinib and none for dabrafenib+trametinib) in a phase III trial. Among our 42 patients treated by TTC between January 2014 and March 2017, 4.8% (2/42) of those treated in the first line presented severe skin rash versus 19% (8/42) of patients treated in the second line after previous immunotherapy. In particular, we observed one case of Stevens–Johnson syndrome and four cases of severe drug reaction with eosinophilia and systemic symptoms syndrome under TTC in patients who had received immunotherapy previously. Thus, previous immunotherapy appears to play an important role in the skin rash onset and severity induced by TTC.
Systematic Review of Surgical Treatment and Outcomes After Local Surgery of Primary Cutaneous Melanomas of the Penis and Scrotum
Authors: Bittar Julie M. , Bittar Peter G. , Wan Marilyn T. , Kovell Robert C. , Guzzo Thomas J. , Shin Thuzar M. , Etzkorn Jeremy R. , Sobanko Joseph F. , Miller Christopher J.
Published: July 2018

BACKGROUND

Few data exist to guide surgical management and counseling about local recurrence after surgery of primary male genital melanoma.

OBJECTIVE

To compile all available data on local recurrence rates after surgery of primary cutaneous melanoma of the penis and scrotum.

MATERIALS AND METHODS

A systematic review of PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Excerpta Medica database (EMBASE), and Web of Science identified all surgically treated penile and scrotal melanomas that reported local recurrence status and follow-up time.

RESULTS

One hundred twenty-seven melanomas from 74 manuscripts were included. Eighty-six percent of melanomas were located on the penis, and 14% were located on the scrotum. Average follow-up time was 35.7 months. Scrotal melanomas were predominantly treated with organ-sparing surgeries (16/18, 88.9%), whereas penile melanomas were treated more often with amputation (61/109, 56.0%). Overall, local recurrence rate was 15.7% (20/127). Local recurrence rates for penile cases were 18.8% (9/48) after organ-sparing surgery versus 13.1% (8/61) for amputative surgery. Local recurrence rates were 66.7% (4/6) after positive surgical margins versus 10.2% (5/49) after negative surgical margins.

CONCLUSION

Local recurrence rates are high after both organ-sparing and amputative surgery of primary cutaneous melanoma of the penis and scrotum. There is a need to standardize reporting for this rare tumor, as more complete data are necessary to develop consensus guidelines for surgical management of male genital melanoma.
Residential exposure to fine particulate matter air pollution and incident breast cancer in a cohort of Canadian women
Authors: Villeneuve Paul J. , Goldberg Mark S. , Crouse Dan L. , To Teresa , Weichenthal Scott A. , Wall Claus , Miller Anthony B.
Published: July 2018

Background:

Air pollution has been classified as a human carcinogen based largely on epidemiological studies of lung cancer. Recent research suggests that exposure to ambient air pollution increases the risk of breast cancer.

Methods:

Our aim was to characterize associations between residential exposure to ambient fine particulate matter (PM2.5) and the incidence of breast cancer in a cohort of 89,247 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985. Vital status and incident cancers were determined through record linkage to the national registry data through 2005. Individual-level estimates of exposures to PM2.5 at baseline were derived from satellite observations. Six thousand five hundred three incident breast cancers were identified during follow-up. We classified menopausal status using self-reported information collected at baseline and by attained age (50, 52, and 54 years) as women were followed-up. We computed hazard ratios (HRs) and their 95% confidence intervals (CI) using age as the time axis. Models were adjusted for several individual risk factors, including reproductive history, as well as census-based neighborhood-level characteristics.

Results:

The median residential concentration of PM2.5 was 9.1 μg/m3. In models adjusted for personal and contextual risk factors, a 10-μg/m3 increase in PM2.5 was associated with an elevated risk of premenopausal (HR = 1.26; 95% CI = 0.99, 1.61) but not postmenopausal breast cancer (HR = 1.01; 95% CI = 0.94, 1.10). The elevated risk of premenopausal breast cancer from PM2.5 was only evident among those randomized to the screening arm of the study.

Conclusions:

Our findings support the hypothesis that exposure to low concentrations of PM2.5 increase the risk of premenopausal breast cancer.
Residential exposure to air pollution and incidence of Parkinson’s disease in a large metropolitan cohort
Authors: Cerza Francesco , Renzi Matteo , Agabiti Nera , Marino Claudia , Gariazzo Claudio , Davoli Marina , Michelozzi Paola , Forastiere Francesco , Cesaroni Giulia
Published: July 2018

Background:

The literature on air pollution exposure and Parkinson’s disease (PD) reported controversial results. The aim of this study is to analyze the association of exposure to particulate matter (PM10, PM2.5, PM2.5–10, PM2.5 absorbance), nitrogen oxides (NO2, NOx), and ozone (O3) with incidence of PD in a large administrative cohort.

Methods:

We followed 1,008,253 patients who are 50+-year-old residents in Rome (free from PD) from January 2008 to December 2013. We identified new cases of PD using data from several sources including drug prescriptions and hospital discharges. We estimated exposure at residence using land use regression models for particulate matter and nitrogen oxides, and a chemical dispersion model for summer ozone. We used Cox models (hazard ratio [HR]) to estimate the association between air pollution exposure and incidence of PD, adjusting for individual and contextual variables.

Results:

There were 13,104 new cases of PD during the follow-up. There was no evidence of a positive association between particulate matter exposure and PD. There was a negative association between PM absorbance, nitrogen oxides exposure, and incidence of PD with HR = 0.97 (95% confidence interval [CI] = 0.96, 0.99) per 10 μg/m3 increase in NO2 and HR = 0.97 (95% CI = 0.96, 0.98) per 20 μg/m3 increase in NOx. Long-term exposure to ozone was positively associated with incidence of PD, HR = 1.02 (95% CI = 1.00, 1.05) per 10 μg/m3 increase in summer ozone.

Conclusions:

Incidence of PD was not related to PM exposure in this study and a negative association was found for nitrogen oxides. The association found with ozone is new and should be further investigated.
Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Thrombocytopenia
Authors: Janion-Sadowska Agnieszka , Papuga-Szela Elżbieta , Łukaszuk Robert , Chrapek Magdalena , Undas Anetta
Published: July 2018

Aims:

Thrombocytopenia was one of the exclusion criteria in randomized trials in which non–vitamin K antagonist oral anticoagulants (NOACs) were tested. The safety of NOACs in patients with atrial fibrillation (AF) and thrombocytopenia remains unclear.

Methods:

We studied 62 patients with AF aged from 53 to 85 (mean 70.5) years with platelet count from 50 to 100 × 109/L who were treated with rivaroxaban 15 mg once daily (33.9%), dabigatran 110 mg twice daily (bid) (54.8%), or apixaban 2.5 mg bid (11.3%). Age- and sex-matched AF patients with normal platelet count and similar CHA2DS2-VASc scores who were treated with the recommended doses of NOACs served as a reference group.

Results:

Patients were followed for a mean of 55 months (range, 23–64 months). In the thrombocytopenia group bleeding risk was higher (mean HAS-BLED score 2.0, vs. 1.0, P < 0.0001). During follow-up in thrombocytopenic and normocytopenic patients, we observed similar rates of major bleeding (1.8%/year vs. 2.7%/year, P = 0.49), clinically relevant nonmajor bleeding (CRNMB) (1.5%/year vs. 1.1%/year, P = 0.74), ischemic stroke and transient ischemic attacks (1.8%/year vs. 1.5%/year, P = 0.8), and death (1.06%/year vs. 1.11%/year, P = 0.96). The risk of bleeding and stroke was unaffected by the type of the NOAC used in both groups. Major bleedings and clinically relevant nonmajor bleeding in thrombocytopenic patients on NOACs were predicted only by age (hazard ratio 1.1, 95% confidence interval 1.0–1.3, P = 0.04).

Conclusions:

Our findings indicate that in AF patients with mild thrombocytopenia, anticoagulation with NOAC at reduced doses seems to be safe and effective.
Pediatric Thyroid Eye Disease: Clinical Characteristics and Orbital Decompression Outcomes
Authors: Chua Michael R. , Tomlinson Lauren A. , Binenbaum Gil , Katowitz William R.
Published: July 2018

Purpose:

To review the clinical presentation, disease severity, and surgical interventions of children with thyroid eye disease (TED) at a single institution over a 7-year period.

Methods:

Retrospective cohort study of children 0 to 18 years of age with a diagnosis of TED, seen at the Children’s Hospital of Philadelphia from 2009 to 2016. Ophthalmic examination findings, neuroimaging study results, and ophthalmological management were recorded. t-Tests were used to test for statistical significance. Institutional Review Board approval was obtained for the study.

Results:

Sixty-seven subjects with pediatric TED were studied: 59 female and 8 male. The mean age at diagnosis was 11.6 years (SD 4.2, range 2.3–17.9). All subjects had proptosis (67, 100%). Other clinical findings were eyelid retraction in 46 (69%), chemosis in 7 (10%), punctate epithelial erosions in 8 (12%), and strabismus in 1 (1.5%). No subjects had evidence of optic neuropathy. Five subjects with static-phase TED received orbital decompression surgery for exposure keratopathy and disfigurement. All had significant cosmetic improvement and resolution of exposure keratopathy.

Discussion:

In this series, children with TED generally exhibit mild ocular signs, which is in agreement with past studies. Our study presented a high incidence of proptosis compared with other studies; however, this may represent a referral bias to our quaternary care center.

Conclusion:

Pediatric TED patients exhibit mild symptoms, such as proptosis and eyelid retraction without strabismus, vision loss, or optic neuropathy. Some children with TED have severe disfigurement and corneal exposure due to the disease and benefit from orbital decompression.
Vasopressor Infusion After Subarachnoid Hemorrhage Does Not Increase Regional Cerebral Tissue Oxygenation
Authors: Yousef Khalil M. , Crago Elizabeth , Chang Yuefang , Lagattuta Theodore F. , Mahmoud Khadejah , Shutter Lori , Balzer Jeffrey R. , Pinsky Michael R. , Friedlander Robert M. , Hravnak Marilyn
Published: July 2018

Introduction: Vasopressors are commonly used after aneurysmal subarachnoid hemorrhage (aSAH) to sustain cerebral pressure gradients. Yet, the relationship between vasopressors and the degree of cerebral microcirculatory support achieved remains unclear. This study aimed to explore the changes in cerebral and peripheral regional tissue oxygen saturation (rSO2) as well as blood pressure (BP) before and after vasopressor infusion in patients with aSAH. Methods: Continuous noninvasive cerebral and peripheral rSO2 was obtained using near-infrared spectroscopy for up to 14 days after aSAH. Within-subject differences in rSO2 before and after the commencement of vasopressor infusion were analyzed controlling for Hunt and Hess grade and vasospasm. Results: Of 45 patients with continuous rSO2 monitoring, 19 (42%) received vasopressor infusion (all 19 on norepinephrine, plus epinephrine in 2 patients, phenylephrine in 4 patients, and vasopressin in 2 patients). In these 19 patients, their vasopressor infusion times were associated with higher BP (systolic [b = 15.1], diastolic [b = 7.3], and mean [b = 10.1]; P = .001) but lower cerebral rSO2 (left cerebral rSO2 decreased by 4.4% [b = −4.4, P < .0001]; right cerebral rSO2 decreased by 5.5% [b = −5.5, P = .0002]). Conclusions: Despite elevation in systemic BP during vasopressor infusion times, cerebral rSO2 was concurrently diminished. These findings warrant further investigation for the effect of induced hypertension on cerebral microcirculation.
Stroke Education Video Does Not Affect Patient Satisfaction Scores: A System Analysis
Authors: Meighan Melissa M.
Published: July 2018

With limited time and resources in the acute care hospital, the most effective methods of stroke education are crucial. A combination of methods of one-on-one counseling or teaching, print, and video has been shown to have the greatest effect. Video education is a component of a combination educational approach. This evaluation from a large integrated system comprising 21 medical facilities compared patient satisfaction data with stroke education from 5 facilities that have video educational services and print materials and 17 facilities that provide print materials only. All 21 facilities provided additional teaching by the nurse. From this evaluation, it seems that there may be no relationship between video or kiosk equipment on patient satisfaction scores for this integrated system.
Use of Plasma-Based Trauma Transfusion Protocols at Level IV Trauma Centers
Authors: Harris Charles T. , Dudley Brittney M. , Davenport Daniel , Higgins Jacob , Fryman Lisa , Bernard Andrew
Published: July 2018

Early initiation of a high ratio massive transfusion can lower trauma patient mortality by 80%. Long transport times from rural Level IV trauma centers therefore require that damage control resuscitation begin before patient transfer. This study evaluates the current use of fresh frozen plasma (FFP) at Level IV trauma centers and the feasibility of implementing trauma transfusion protocols at these centers. Demographic and clinical data were collected for trauma patients at all state Level IV trauma centers who would have met criteria for massive transfusion protocol (MTP) activation based on the Assessment of Blood Consumption (ABC) score. All state Level IV trauma centers were also surveyed to determine availability of blood bank plasma resources. A total of 760 adult trauma patients presented to a Level IV trauma center during the study period. Three hundred sixty-eight patients (48.4%) were transferred to a higher level of care. Because FAST (Focused Assessment with Sonography for Trauma) results were not available in the state registry data, we included all blunt trauma patients with an ABC score of 1 as “potential ABC-positive patients.” Forty-two (5.5%) patients were potentially ABC positive. Fifteen of 22 Level IV centers responded to our survey. Seventy-three percent of respondents have FFP available. Mean time to FFP availability was 63.1 min. Median total length of stay from registration to emergency department discharge for potentially ABC-positive patients was 2 hr. Because most Level IV trauma centers have FFP and thaw times are such that administration would not delay transport to a higher level of care, we recommend implementation of MTPs at Level IV trauma centers to reduce hemorrhage-associated mortality.
Geriatric Trauma Protocol
Authors: Cortez Renee
Published: July 2018

Study design for a quality improvement project. Objective was to implement a geriatric trauma protocol (GTP) based on American College of Surgeons recommendations to improve patient outcomes. Geriatric trauma patients comprise a vulnerable and high-risk trauma population, and must be treated with specific protocols that take into account physiological, psychosocial, environmental, and pharmacological needs. A growing body of research and organizations such as the American College of Surgeons and the Eastern Association for the Surgery of Trauma recommend that a specific trauma protocol for geriatric adults must be utilized in hospitals and trauma centers. A retrospective chart review was conducted to assess geriatric patient outcomes prior to GTP implementation. Surgical residents then received training on the GTP, including performing additional diagnostics, referrals, and discussing goals of care early in treatment. The GTP was then implemented for 8 weeks and monitored to determine its effects on patient outcomes. The training for surgical residents in the GTP yielded a 9.2% increase in provider knowledge. The results of the GTP showed a reduced length of stay and increased geriatric consultations. More patients received a full evaluation by the trauma team, contributing the reduced length of stay. The use of a GTP shows promise in being able to improve patient outcomes, including morbidity and mortality. The principles of the GTP can be applied in all clinical settings, especially emergency rooms, which are on the frontlines of initial evaluations. In order to improve health care delivery to an aging population, organizations and clinicians should adopt a specialized GTP into their practices.