bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Noble Truths
Authors: Anderson Carol S.
Published: August 2016

The Buddhist teaching known in English as the four noble truths is most often understood as the single most important teaching of the historical buddha, Siddhartha Gautama, who taught in northern India during the 5th century bce. —Sanskrit duḥkha and Pali dukkha (pain), samudayo (arising), nirodho (ending), and maggo (path) or dukkhanirodhagāminī paṭipadā (way leading to the ending of pain)—are recorded in the languages of Pali and Sanskrit in the different Buddhist canons, and the literary traditions have been very consistent in how they remember the teaching. These teachings are explained in the Sutta on the Turning of the Dhamma Wheel (Dhamma-cakka-ppavattana Sutta in Pali) and in a handful of different formulations in different suttas, abhidhamma analysis, and in the vinaya sections of the canonical texts. Despite the widespread awareness of the four truths, the complexities associated with this teaching are not usually recognized. While the bulk of the scholarship on the four noble truths analyzes them as they appear in the Pali canon, recent scholarship traces them through Buddhist canons that are extant in the Chinese Tripitaka.
Mysticism in Martin Luther’s Development and Thoughts
Authors: Leppin Volker
Published: August 2016

Martin Luther’s spiritual and theological development was deeply rooted in mystical traditions. During his early years as an Augustinian friar, he experienced mystical visions following the paths of Dionysian mysticism, while a few years later he was inspired by Ps-Bonaventure, Bernard of Clairvaux, and John Tauler. His early theology of penitence, as expressed in the Ninety-five Theses, derived from these sources, as did his description of justification in the image of bride and bridegroom in his tract On the Liberty of a Christian. Even more so, central elements in his theology were shaped by mystical influences, including his distinction between Law and Gospel, the doctrine of justification, and the concept of the priesthood of all believers. Thus, Luther’s theology should be seen as a reception and development deriving from the mystical discourse of the later Middle Ages.
Martin Luther, Philip Melanchthon, and Their Wittenberg Colleagues
Authors: Wengert Timothy J.
Published: August 2016

The German Reformation, sparked by the publication of Martin Luther’s 95 Theses in 1517, unfolded parallel to another intellectual phenomenon then sweeping centers of higher education throughout western Europe: the development of a new way to read classic literature of the humanities, philosophy, and theology, often called Renaissance humanism. At the University of Wittenberg, this resulted in the development of a sodality of professors in the arts and theology faculties, initially including Andreas Bodenstein (Karlstadt), Nicholas von Amsdorf, Martin Luther, and the court’s university advisor, Georg Spalatin, but quickly spreading to include, by the early 1520s, Philip Melanchthon, Justus Jonas, and Johannes Bugenhagen, among others. Any attempt to understand the early phases of Wittenberg’s Reformation without taking into account this sodality will ultimately fail to catch the breadth of this movement and the commitment of these teachers to one another and to their cause. After an early skirmish over theological method resulted in Karlstadt’s distancing of himself from the university, the other faculty members remained committed to reforming the curricula of the arts and higher faculties at the university along humanist, evangelical lines. This reform influenced the theology and practice of the emerging church in Saxony and elsewhere, witnessed among other places in the 1527–1528 Visitation Articles, and led to a uniquely Wittenberg reform, one that always blended the highest regard for good letters and the most ancient sources with a developing Lutheran theology.
Border Wars in South America during the 19th Century
Authors: Henderson Peter V. N.
Published: August 2016

While Europeans basked in the glory of their so-called century of peace between the end of the Napoleonic wars (1815) and the onset of World War I (1914), Latin Americans knew no such luxury. Conflict became a way of life for Latin Americans attempting to construct nation-states. Liberals and Conservatives dueled with one another for political power, while caudillos (military strongmen) added their unique twisted logic to the political process. Historians have spilled considerable ink detailing these internal conflicts that complicated Latin America’s struggle for effective state formation in the early national period but have paid much less attention to the external wars over disputed boundaries that involved every South American nation during the 19th century. As historian Robert Burr described it: boundary conflicts were the “congenital international disease of Spain’s former colonies.”
PathScore: a web tool for identifying altered pathways in cancer data
Authors: Gaffney Stephen G. , Townsend Jeffrey P.
Published: August 2016

Summary:  PathScore quantifies the level of enrichment of somatic mutations within curated pathways, applying a novel approach that identifies pathways enriched across patients. The application provides several user-friendly, interactive graphic interfaces for data exploration, including tools for comparing pathway effect sizes, significance, gene-set overlap and enrichment differences between projects.

Availability and Implementation: Web application available at pathscore.publichealth.yale.edu. Site implemented in Python and MySQL, with all major browsers supported. Source code available at: github.com/sggaffney/pathscore with a GPLv3 license.

Contact:  stephen.gaffney@yale.edu
BiDiFuse: a FIJI plugin for fusing bi-directionally recorded microscopic image volumes
Authors: Detrez Jan R. , Vanderwinden Jean-Marie , Barbier Michaël , Verschuuren Marlies , Nuydens Rony , Langlois Xavier , Timmermans Jean-Pierre , De Vos Winnok H.
Published: August 2016

Summary: Deep tissue imaging is increasingly used for non-destructive interrogation of intact organs and small model organisms. An intuitive approach to increase the imaging depth by almost a factor of 2 is to record a sample from two sides and fuse both image stacks. However, imperfect three-dimensional alignment of both stacks presents a computational challenge. We have developed a FIJI plugin, called BiDiFuse, which merges bi-directionally recorded image stacks via 3D rigid transformations. The method is broadly applicable, considering it is compatible with all optical sectioning microscopes and it does not rely on fiducial markers for image registration.

Availability and Implementation: The method is freely available as a plugin for FIJI from https://github.com/JanDetrez/BiDiFuse/.

Contact:  winnok.devos@uantwerpen.be
RNAcommender: genome-wide recommendation of RNA–protein interactions
Authors: Corrado Gianluca , Tebaldi Toma , Costa Fabrizio , Frasconi Paolo , Passerini Andrea
Published: August 2016

Motivation: Information about RNA–protein interactions is a vital pre-requisite to tackle the dissection of RNA regulatory processes. Despite the recent advances of the experimental techniques, the currently available RNA interactome involves a small portion of the known RNA binding proteins. The importance of determining RNA–protein interactions, coupled with the scarcity of the available information, calls for in silico prediction of such interactions.

Results: We present RNAcommender, a recommender system capable of suggesting RNA targets to unexplored RNA binding proteins, by propagating the available interaction information taking into account the protein domain composition and the RNA predicted secondary structure. Our results show that RNAcommender is able to successfully suggest RNA interactors for RNA binding proteins using little or no interaction evidence. RNAcommender was tested on a large dataset of human RBP-RNA interactions, showing a good ranking performance (average AUC ROC of 0.75) and significant enrichment of correct recommendations for 75% of the tested RBPs. RNAcommender can be a valid tool to assist researchers in identifying potential interacting candidates for the majority of RBPs with uncharacterized binding preferences.

Availability and Implementation: The software is freely available at http://rnacommender.disi.unitn.it.

Contact:  gianluca.corrado@unitn.it or andrea.passerini@unitn.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes
Authors: Wheeler Nicole E. , Barquist Lars , Kingsley Robert A. , Gardner Paul P.
Published: August 2016

Motivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predicting the functional significance of this variation is a difficult task. While many comparative genomics studies have focused on gene flux and large scale changes, relatively little attention has been paid to quantifying the effects of single nucleotide polymorphisms and indels on protein function, particularly in bacterial genomics.

Results: We present a hidden Markov model based approach we call delta-bitscore (DBS) for identifying orthologous proteins that have diverged at the amino acid sequence level in a way that is likely to impact biological function. We benchmark this approach with several widely used datasets and apply it to a proof-of-concept study of orthologous proteomes in an investigation of host adaptation in Salmonella enterica. We highlight the value of the method in identifying functional divergence of genes, and suggest that this tool may be a better approach than the commonly used dN/dS metric for identifying functionally significant genetic changes occurring in recently diverged organisms.

Availability and Implementation: A program implementing DBS for pairwise genome comparisons is freely available at: https://github.com/UCanCompBio/deltaBS.

Contact:  nicole.wheeler@pg.canterbury.ac.nz or lars.barquist@uni-wuerzburg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Transfusion-free treatment strategies for acute anemia in critical care
Authors: Morgan Caitlin A. , Byul (Sarah) Sae , Forest Christopher P.
Published: August 2016

Acute anemia is a frequently encountered diagnosis in critically ill patients, and can be a challenge if blood products are not readily available or if patients refuse these products on the basis of their religious beliefs. This article discusses the goals of anemia management and summarizes several alternatives to blood transfusions that can be used to prevent and treat acute anemia.
Recognizing and managing common foot injuries
Authors: Gocke Thomas V.
Published: August 2016

Subtle signs of foot and ankle fractures are often overlooked on initial radiographs. This article describes several commonly missed foot and ankle injuries and provides help in reviewing radiographs and identifying foot and ankle fractures.
Diagnostic utility of challenge procedures for physical urticaria/angioedema syndromes: a systematic review
Authors: Cuervo-Pardo Lyda , Gonzalez-Estrada Alexei , Lang David M.
Published: August 2016

Purpose of review

Physical urticaria/angioedema syndromes (PUAs) are commonly encountered. They are identified by a history of physical factors provoking cutaneous symptoms, and confirmed by provocation testing. Recent guidelines have recommended use of challenge procedures for diagnosis; however, their positive/negative likelihood ratios have not been established.

Recent findings

We conducted a systematic review to determine the diagnostic utility of recommended office procedures for three common PUAs: dermatographia (DERMATO), cholinergic urticaria (CHOL), and delayed pressure urticaria/angioedema (DPUA). In this study, we were unable to identify studies of sufficient methodologic quality to calculate positive/negative likelihood ratios for recommended diagnostic challenges for PUAs.

The study highlights the need for well designed studies to aid the clinician in interpretation of diagnostic challenges for patients with DERMATO, CHOL, and DPUA. There are limited high-quality data available to support the diagnostic utility of office challenges for PUAs. There is a low sensitivity associated with methacholine intradermal challenge for confirming a diagnosis of CHOL.
The rich and the poor: environmental biodiversity protecting from allergy
Authors: Ruokolainen Lasse , Fyhrquist Nanna , Haahtela Tari
Published: August 2016

Purpose of review

It has been proposed that biodiversity loss leads to reduced interaction between environmental and human microbiotas. This, in turn, may lead to immune dysfunction and impaired tolerance mechanisms in humans. That is, contact with environmental biodiversity is expected to protect from allergies. However, direct evidence linking contact with biodiversity and risk of allergy has been lacking. In this review, we consider the latest research on the biodiversity hypothesis of allergy.

Recent findings

It is becoming clear that what you eat, drink, inhale, and touch all contribute to the grand scheme of host–microbial crosstalk that is needed for a balanced, healthy immune system to develop and maintain a healthy recognition between harmful and harmless invasions. Microbes can either communicate directly with host immune cells or affect the host via metabolism that can even lead to epigenetic modifications. Our living environment plays a key role in this process. Although especially, early exposure to diverse, beneficial microbiota from the environment is repeatedly found crucial, studies on immigrants demonstrate that condition in later life can also be decisive.

Conclusion

We are still lacking a more detailed understanding of the interaction between natural, environmental biodiversity, and health, which calls for new innovative and more long-term investigations. The outcomes should be utilized in policy and urban planning efforts, promoting human interaction with natural biodiversity, and supporting a healthy lifestyle.
Connecting Education to Quality: Engaging Medical Students in the Development of Evidence-Based Clinical Decision Support Tools
Authors: Crabtree Elizabeth A. , Brennan Emily , Davis Amanda , Squires Jerry E.
Published: August 2016

Problem

Evidence-based practice (EBP) skills are crucial for delivering high-quality patient care. It is essential that medical students learn EBP concepts through a practical, in-depth research project. To date, literature on preparing students in this manner is limited.

Approach

In academic year 2014–2015, the Medical University of South Carolina’s (MUSC’s) Center for Evidence-Based Practice (now known as the Value Institute) partnered with College of Medicine faculty to revitalize the undergraduate medical student EBP curriculum. Without adding to the number of the lecture hours, the curriculum was restructured to be more process driven, project based, and clinically relevant. The resulting yearlong EBP course partnered small teams of medical students with interprofessional clinical teams to engage the students in developing evidence-based clinical decision support tools.

Outcomes

The content developed during the EBP projects is currently being used to develop evidence-based clinical practice guidelines and accompanying order sets.

Next Steps

It is likely that this model will serve as a new framework for guideline development and will greatly expand the breadth of evidence-based content currently produced and available for clinicians at the MUSC. It would be feasible to offer a similar course within the MUSC to other disciplines and colleges, or at other institutions, if there were support from administration, interest on the part of clinicians and medical faculty, and individuals with the required expertise available to develop the curriculum and facilitate the course. It is worth considering how to improve the course and evaluating opportunities to implement it within other settings.
Brief Opioid Overdose Knowledge (BOOK): A Questionnaire to Assess Overdose Knowledge in Individuals Who Use Illicit or Prescribed Opioids
Authors: Dunn Kelly E. , Barrett Frederick S. , Yepez-Laubach Claudia , Meyer Andrew C. , Hruska Bryce J. , Sigmon Stacey C. , Fingerhood Michael , Bigelow George E.
Published: August 2016

Background:

Opioid overdose is a public health crisis. This study describes efforts to develop and validate the Brief Opioid Overdose Knowledge (BOOK) questionnaire to assess patient knowledge gaps related to opioid overdose risks.

Methods:

Two samples of illicit opioid users and a third sample of patients receiving an opioid for the treatment of chronic pain (total N = 848) completed self-report items pertaining to opioid overdose risks.

Results:

A 3-factor scale was established, representing Opioid Knowledge (4 items), Opioid Overdose Knowledge (4 items), and Opioid Overdose Response Knowledge (4 items). The scale had strong internal and face validity. Patients with chronic pain performed worse than illicit drug users in almost all items assessed, highlighting the need to increase knowledge of opioid overdose risk to this population.

Conclusions:

This study sought to develop a brief, internally valid method for quickly assessing deficits in opioid overdose risk areas within users of illicit and prescribed opioids, to provide an efficient metric for assessing and comparing educational interventions, facilitate conversations between physicians and patients about overdose risks, and help formally identify knowledge deficits in other patient populations.
Bupropion “Abuse” Reported to US Poison Centers
Authors: Stassinos Gina L , Klein-Schwartz Wendy
Published: August 2016

Objectives:

Bupropion use to obtain nonmedical psychoactive effects has been reported. The objective was to determine the prevalence, characteristics, clinical effects, and outcomes of bupropion “abuse.”

Methods:

A 14-year retrospective review was conducted of single substance bupropion cases with “intentional abuse” as the coded reason for exposure in individuals 13 and older reported to the National Poison Data System. Data were evaluated for prevalence, demographics, clinical effect, route, final management site, and coded outcome.

Results:

There were 975 bupropion abuse cases, which accounted for 3.3% of single substance bupropion cases reported to US poison centers. The prevalence of abuse increased by 75%, from 2000 to 2012, declining slightly in 2013. The majority of cases were 13 to 29 years old (67.4%). The most frequent clinical effects were tachycardia (57.0%), seizures (33.5%), agitation/irritable (20.2%), hallucinations/delusions (14.0%), and tremor (13.1%). Most exposures were ingestions (745) followed by insufflation (166), parenteral (17), and other/unknown (17); 30 cases involved 2 routes. Seizure frequency was not significantly different between routes (P = 0.783) or exposure chronicity (P = 0.264). Final management sites were predominantly emergency department (36.9%) and admission to critical care unit (27.3%) or noncritical care unit (20.1%). Outcomes were major (11.4%), moderate (48.2%), minor (24.5%), and no effect (15.5%). There were 4 deaths.

Conclusions:

Most bupropion abuse occurs in adolescents and young adults. Tachycardia and seizures are common indicating the potential for serious effects. Seizures occur regardless of route. Providers should be aware of risk of bupropion abuse.
Sex Differences in the Association Between Internalizing Symptoms and Craving in Methamphetamine Users
Authors: Hartwell Emily E. , Moallem Nathasha R. , Courtney Kelly E. , Glasner-Edwards Suzette , Ray Lara A.
Published: August 2016

Objectives:

Methamphetamine (MA) users often have substantial psychiatric comorbidities, with nearly a third reporting lifetime mood disorders and over a quarter reporting lifetime anxiety disorders. Female MA users are more likely to endorse depression and anxiety symptoms compared with men. Craving has been related to mood/anxiety symptoms in MA users. To extend the literature on sex differences in MA use disorder, the present study examines the role of sex as a moderator of the relationship between mood/anxiety symptoms and MA craving.

Methods:

Participants (N = 203) were nontreatment-seeking, current MA users, recruited from the Los Angeles community for enrollment in a larger pharmacotherapy trial. At the assessment visit, participants completed multiple measures including the Methamphetamine Urge Questionnaire, the Beck Depression Inventory, and the Beck Anxiety Inventory.

Results:

The relationship between depression symptomatology and MA craving was moderated by sex (F = 6.18, P = 0.01), such that the relationship was positive and significant for men (P < 0.001), but was not significant for women. Similarly, sex significantly moderated the relationship between anxiety and MA craving (F = 5.99, P = 0.02), such that the relationship was also positive and significant in men, but not in women (P < 0.001).

Conclusions:

These results suggest that men may be more sensitive to the effects of internalizing symptoms on MA craving than women. Given craving's propensity to predict relapse, these initial findings indicate the necessity of treating comorbid psychiatric problems in male MA users, which may in turn assist in the attenuation of craving.
Acceptance and Commitment Therapy (ACT) for Chronic Pain
Authors: Hughes Laura S. , Clark Jodi , Colclough Janette A. , Dale Elizabeth , McMillan Dean
Published: August 2016

Objectives:

Chronic pain places a burden on individuals and the economy. Although there is evidence for the effectiveness of cognitive-behavior therapy, it is recognized that the effects are limited. Acceptance and Commitment Therapy (ACT), which aims to increase valued action in the presence of pain, has been suggested as an alternative approach. The objective of this review was to determine the clinical effectiveness of ACT for chronic pain in adults when compared with control conditions and other active treatments.

Methods:

The searches of this systematic review were conducted in the Cochrane library, MEDLINE, EMBASE, CINAHL Plus (EBSCO), and PsycINFO. Grey literature, reference list, and reverse citation searches were also completed.

Results:

Eleven trials were included. ACT was favored over controls (no alternative intervention or treatment as usual). Significant, medium to large effect sizes were found for measures of pain acceptance and psychological flexibility, which are typically considered processes of ACT. Significant small to medium effect sizes were found for measures of functioning, anxiety, and depression. Measures of pain intensity and quality of life were not significantly different than zero. Generally effect sizes were smaller at follow-up.

Discussion:

ACT was more clinically effective than controls on a number of outcomes. It is possible that methodological limitations, some of which are common to psychological trials, may have led to overestimated effects. Only a few studies compared ACT to active treatments and while the evidence is promising for ACT in the treatment of chronic pain, further methodologically robust trials are required.
Success of Intubation Rescue Techniques after Failed Direct Laryngoscopy in Adults
Authors: Aziz Michael F. , Brambrink Ansgar M. , Healy David W. , Willett Amy Wen , Shanks Amy , Tremper Tyler , Jameson Leslie , Ragheb Jacqueline , Biggs Daniel A. , Paganelli William C. , Rao Janavi , Epps Jerry L. , Colquhoun Douglas A. , Bakke Patrick , Kheterpal Sachin
Published: August 2016

Background

Multiple attempts at tracheal intubation are associated with mortality, and successful rescue requires a structured plan. However, there remains a paucity of data to guide the choice of intubation rescue technique after failed initial direct laryngoscopy. The authors studied a large perioperative database to determine success rates for commonly used intubation rescue techniques.

Methods

Using a retrospective, observational, comparative design, the authors analyzed records from seven academic centers within the Multicenter Perioperative Outcomes Group between 2004 and 2013. The primary outcome was the comparative success rate for five commonly used techniques to achieve successful tracheal intubation after failed direct laryngoscopy: (1) video laryngoscopy, (2) flexible fiberoptic intubation, (3) supraglottic airway as part of an exchange technique, (4) optical stylet, and (5) lighted stylet.

Results

A total of 346,861 cases were identified that involved attempted tracheal intubation. A total of 1,009 anesthesia providers managed 1,427 cases of failed direct laryngoscopy followed by subsequent intubation attempts (n = 1,619) that employed one of the five studied intubation rescue techniques. The use of video laryngoscopy resulted in a significantly higher success rate (92%; 95% CI, 90 to 93) than other techniques: supraglottic airway conduit (78%; 95% CI, 68 to 86), flexible bronchoscopic intubation (78%; 95% CI, 71 to 83), lighted stylet (77%; 95% CI, 69 to 83), and optical stylet (67%; 95% CI, 35 to 88). Providers most frequently choose video laryngoscopy (predominantly GlideScope® [Verathon, USA]) to rescue failed direct laryngoscopy (1,122/1,619; 69%), and its use has increased during the study period.

Conclusions

Video laryngoscopy is associated with a high rescue intubation success rate and is more commonly used than other rescue techniques.
Randomized, Prospective Comparison of Bioabsorbable and Steel Screw Fixation of Lisfranc Injuries
Authors: Ahmad Jamal , Jones Kennis
Published: August 2016

Objective:

This study's objective is to compare outcomes of bioabsorbable versus steel screws for treating Lisfranc injuries.

Design:

This research was conducted in a prospective and randomized manner between September 2008 and December 2013.

Setting:

This study was performed in the outpatient setting at a tertiary-level care center in a single surgeon's practice.

Patients/Participants:

Forty patients with acute Lisfranc injuries, amenable to open reduction and screw fixation, enrolled and presented for final follow-up.

Intervention:

Through randomization, 20 and 20 patients received bioabsorbable versus steel screws, respectively.

Outcome Measurements:

Function and pain were graded using the Foot and Ankle Ability Measures (FAAM) and a visual analog scale of pain. Radiographs were assessed for joint stability and degeneration.

Results:

For those with steel screws, the mean FAAM score increased from 24.9 to 89.6 of 100 and pain score decreased from 6.5 to 1.9 of 10 by latest follow-up. For those with absorbable screws, the mean FAAM score increased from 32.5 to 91.2 and pain score decreased from 4.7 to 1.3 by latest follow-up. These differences in final mean function (P = 0.4) and pain (P = 0.25) between the study groups were not statistically significant. Final radiographs showed no Lisfranc instability in any study patients, but rather midfoot arthritis in 4 and 2 patients with steel versus bioabsorbable screws, respectively. None of the patients who received steel screws had hardware-related problems, but 1 patient who received absorbable fixation developed an inflammatory reaction at a nonresorbed screw head at 2 years after surgery.

Conclusions:

Bioabsorbable screws provide short-term results that are comparable and not significantly different from steel screws for treating unstable Lisfranc injuries. Both methods are predictable in improving function and pain, but using absorbable screws eliminates the need for hardware removal after such trauma.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Recurrent Bacille Calmette–Guérin osteomyelitis with ankle joint involvement in a toddler: gait analysis and rehabilitation experience
Authors: Chen Yen-Chun , Wen Hsin-Chiao , Chen Yen-Chun , Wei Ta-Sen , Chen Kuan-Lin
Published: August 2016

Bacille Calmette–Guérin (BCG) osteomyelitis is a rare complication after vaccination. This article reports on a 1-year-old immunocompetent boy with recurrent BCG osteomyelitis involving the distal tibia who presented with a limping gait from the beginning of toddling. The lesion was located in the metaphysis and crossed the growth plate to the epiphysis, causing concern for ambulation. After surgery, he was initiated on an individualized, intense rehabilitation program and achieved a good functional recovery. Rehabilitation programs with gait analyses provide effective therapeutic and monitoring methods for toddlers recovering from BCG osteomyelitis.
Perioperative Complication Rates in Pediatric Total Joint Arthroplasty Patients Compared With Adults: Results of a Matched Cohort Study
Authors: Van Doren Bryce A. , Odum Susan M. , Casey Virginia F.
Published: August 2016

Background:

One of the least studied areas in orthopaedics is total joint arthroplasty (TJA) in pediatric patients. Recent studies have confirmed that these procedures are being performed on pediatric patients, making it critical to understand the rates of surgical complications in this patient population. We sought to examine the frequency in which surgical complications occur in pediatric patients, aged 20 and younger, undergoing TJA compared with adults.

Methods:

Data from the 2003 to 2012 Kids’ Inpatient Database (ages 20 and younger) and 2002 to 2013 National Inpatient Sample (ages 21 and over) were analyzed. Pediatric patients were matched to 3 adult controls (1 per age group: 21 to 50, 51 to 65, and over 65 y) using patient characteristics including sex, race, orthopaedic diagnosis, and preoperative loss of function. Comparisons were then made between the rates and relative risks (RRs) of surgical complications between pediatric and adult patients. Finally, we examined patient factors associated with surgical complications, utilizing modified Poisson regression models with robust SEs.

Results:

Three adult controls (ie, 1 control from each age group) were identified for 1385 pediatric patients, for a total sample of 5540 TJA patients. Approximately 10% of pediatric patients experienced either major or minor surgical complications. The overall rate of major complications in pediatric patients was 5.05%, compared with 4.79% in adult controls [RR: 1.06 (0.81 to 1.38), P=0.69]. The overall rate of minor complications in pediatric patients was 5.78%, compared with 5.68% in adult controls [RR: 1.02 (0.80 to 1.30), P=0.78]. When adjusted for patient demographics, the RR of major complications was 49% higher in pediatric patients compared with ages 21 to 50 [RR: 1.49 (1.03 to 2.16), P=0.03] with no statistically significant differences noted for other age groups. For minor complications, the adjusted RR in pediatric patients, compared with any other age group, did not approach statistical significance.

Conclusions:

Pediatric patients undergoing TJA experience major and minor surgical complications at rates comparable with their adult counterparts. Our findings offer important insight on the rates of surgical complications in pediatric TJA patients, which is valuable for preoperative education and consultation with patients and families.

Level of Evidence:

Level III—therapeutic.
Clinical Decision Making
Authors: Goodwin C. Rory , Abu-Bonsrah Nancy , Bilsky Mark H. , Reynolds Jeremy J. , Rhines Laurence D. , Laufer Ilya , Disch Alexander C. , Bozsodi Arpad , Patel Shreyaskumar R. , Gokaslan Ziya L. , Sciubba Daniel M. , Bettegowda Chetan
Published: August 2016

Study Design.

Literature review.

Objective.

To describe advancements in molecular techniques, biomarkers, technology, and targeted therapeutics and the potential these modalities hold to predict treatment paradigms, clinical outcomes, and/or survival in patients diagnosed with primary spinal column tumors.

Summary of Background Data.

Advances in molecular technologies and techniques have influenced the prevention, diagnosis, and overall management of patients diagnosed with cancer. Assessment of genomic, proteomic alterations, epigenetic, and posttranslational modifications as well as developments in diagnostic modalities and targeted therapeutics, although the best studied in nonspinal metastatic disease, have led to increased understanding of spine oncology that is expected to improve patient outcomes. In this manuscript, the technological advancements that are expected to change the landscape of spinal oncology are discussed with a focus on how these technologies will aid in clinical decision-making for patients diagnosed with primary spinal tumors.

Methods.

A review of the literature was performed focusing on studies that integrated next-generation sequencing, circulating tumor cells/circulating tumor DNA, advances in imaging modalities and/or radiotherapy in the diagnosis and treatment of cancer.

Results.

We discuss genetic and epigenetic drivers, aberrations in receptor tyrosine kinase signaling, and emerging therapeutic strategies that include receptor tyrosine kinase inhibitors, immunotherapy strategies, and vaccine-based cancer prevention strategies.

Conclusion.

The wide range of approaches currently in use and the emerging technologies yet to be fully realized will allow for better development of rationale therapeutics to improve patient outcomes.

Level of Evidence: N/A
Long-Term Mental Health Problems After Delirium in the ICU*
Authors: Wolters Annemiek E. , Peelen Linda M. , Welling Maartje C. , Kok Lotte , de Lange Dylan W. , Cremer Olaf L. , van Dijk Diederik , Slooter Arjen J.C. , Veldhuijzen Dieuwke S.
Published: August 2016

Objectives:

To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder.

Design:

Prospective cohort study.

Setting:

Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands.

Patients:

One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay.

Interventions:

None.

Measurements and Main Results:

One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and symptoms of anxiety, depression, and posttraumatic stress disorder. The study population consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, ≥ 8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale with a subscale for depression, ≥ 8). In 220 patients (39%), the Impact of Event Scale 15 item was greater than or equal to 35, indicating a high probability of posttraumatic stress disorder. There was substantial overlap between these mental health problems—63% of the subjects who scored positive for the presence of any three of the mental health problems, scored positive for all three. No association was observed between either a single day or multiple days of delirium and symptoms of anxiety, depression, or posttraumatic stress disorder.

Conclusions:

Although symptoms of anxiety, depression, and posttraumatic stress disorder were found to be common 1 year after critical illness, the occurrence of delirium during ICU stay did not increase the risk of these long-term mental health problems.
Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With Noninvasive Ventilation in Ordinary Wards
Authors: Cabrini Luca , Landoni Giovanni , Bocchino Speranza , Lembo Rosalba , Monti Giacomo , Greco Massimiliano , Zambon Massimo , Colombo Sergio , Pasin Laura , Beretta Luigi , Zangrillo Alberto
Published: August 2016

Objective:

Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality.

Design:

Prospective, observational, pragmatic study.

Setting:

Ordinary wards of a teaching hospital.

Patients:

Consecutive patients treated with noninvasive ventilation for acute respiratory failure.

Interventions:

None.

Measurements and Main Results:

Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with “do-not-resuscitate” status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses.

Conclusions:

Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.
Patient, Process, and System Predictors of Iatrogenic Withdrawal Syndrome in Critically Ill Children*
Authors: Best Kaitlin M. , Wypij David , Asaro Lisa A. , Curley Martha A. Q.
Published: August 2016

Objective:

To generate a multidimensional predictive model of risk factors for iatrogenic withdrawal syndrome in critically ill children.

Design:

Secondary analysis of prospective data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial.

Setting:

PICU.

Patients:

Children who received greater than or equal to 5 days of sedation during mechanical ventilation for acute respiratory failure.

Interventions:

The Randomized Evaluation of Sedation Titration for Respiratory Failure study tested the effect of a nurse-led, goal-directed sedation protocol on clinical outcomes. There was no additional intervention in this secondary analysis.

Measurements and Main Results:

Data included 1,157 children from 31 PICUs. Iatrogenic withdrawal syndrome was defined as having at least two Withdrawal Assessment Tool–Version 1 scores greater than or equal to 3 after the start of opioid weaning. Logistic regression with generalized estimating equations to account for clustering by site was used to evaluate patient, process, and healthcare system risk factors for iatrogenic withdrawal syndrome. Subjects with iatrogenic withdrawal syndrome (544/1,157; 47%) were younger and more likely to have preexisting cognitive or functional impairment. They also received higher sedative doses and longer exposure periods. In multivariable analyses, significant predictors of iatrogenic withdrawal syndrome included younger age, preexisting cognitive impairment, higher preweaning mean daily opioid dose, longer duration of sedation, receipt of three or more preweaning sedative classes, higher nursing workload, and more one-to-one nurse staffing.

Conclusions:

Iatrogenic withdrawal syndrome is common in children recovering from critical illness, and several risk factors are predictive, including patient characteristics, sedative exposure, additional sedative agents, and system-level factors. High-risk patients could be identified before weaning to better prevent iatrogenic withdrawal syndrome among at-risk patients.
Overtreatment of Heparin-Induced Thrombocytopenia in the Surgical ICU*
Authors: Harada Megan Y. , Hoang David M. , Zaw Andrea A. , Murry Jason S. , Volod Oksana , Sun Beatrice J. , Nuño Miriam , Mason Russell , Margulies Daniel R. , Ley Eric J.
Published: August 2016

Objective:

Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated.

Design:

In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores. Heparin-induced thrombocytopenia-positive patients were defined as those with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay (optical density, ≥ 0.40) and positive serotonin release assay results.

Setting:

Urban tertiary medical center.

Patients:

Patients admitted to the surgical and cardiac ICU who were presumed to have heparin-induced thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked immunosorbent assay and serotonin release assay testing between January 1, 2011, and August 1, 2014.

Interventions:

None.

Measurements and Main Results:

A total of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, and serotonin release assay scores. A total of 11 patients (8.1%) had positive serotonin release assay and 80 patients had positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were identified as heparin-induced thrombocytopenia positive. Positive serotonin release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density greater than or equal to 2.0, compared with one of 22 patients (4.5%) with optical density values of 0.85–1.99, and one of 102 patients (1.0%) with optical density values of 0–0.84. Out of 135 patients, 29 patients (21.5%) received treatment with argatroban, lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative patients (15%).

Conclusions:

Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold.
Targeted Consent for Research on Standard of Care Interventions in the Emergency Setting
Authors: Wendler David , Dickert Neal W. , Silbergleit Robert , Kim Scott Y. H. , Brown Jeremy
Published: August 2016

Objectives:

There has been significant debate over what consent process, if any, should be used for clinical trials that compare two or more interventions within the standard of care. Some claim that all clinical trials should obtain in-depth research consent because they use subjects to obtain data for the benefit of future patients. Others argue that clinical trials that are limited to interventions within the standard of care do not need to obtain research consent at all. Settling this debate is especially challenging in the emergency setting. The potential for significant morbidity and mortality provides a strong reason to obtain research consent for standard-of-care trials in the emergency setting. Yet, the emergency setting also introduces significant barriers to traditional in-depth research consent. The present article considers to what extent a targeted consent process can resolve these tensions.

Data Synthesis:

We first identified the ethical goals that are promoted by obtaining consent for standard-of-care research and the barriers to obtaining consent that arise in the emergency setting. We then evaluated whether, despite the barriers, it is possible to develop a targeted consent process that promotes the goals for consent in the context of standard-of-care trials.

Conclusions:

Targeted consent offers an ethically appropriate way to obtain consent for many standard-of-care trials in the emergency setting. For studies subject to U.S. regulations, and those subject to other regulations that include similar consent requirements, targeted consent’s verbal disclosure and written form provide a way to satisfy research regulations without blocking valuable studies. For trials that qualify for a waiver of the consent requirements, targeted consent’s verbal disclosure is preferable to waiving consent, provided a slight delay is consistent with appropriate care, and there is a capacitated patient or surrogate available.
Antiepidermis autoantibodies induced by anti-PD-1 therapy in metastatic melanoma
Authors: Brunet-Possenti Florence , Mignot Sabine , Deschamps Lydia , Descamps Vincent
Published: August 2016

Skin rashes induced by anti-PD-1s are often reported; however, their immunological profiles are currently unknown. We report the case of an atypical eruption induced by pembrolizumab, associated with the occurrence of antiepidermis autoantibodies. As the onset of lesions was concomitant with the favorable tumor response, we suggest that this hybrid rash belongs to a new category of paraneoplastic syndrome, reflecting the intense immunomodulation induced by pembrolizumab. With the increasing use of anti-PD-1s, this kind of report may become frequent. For a better understanding of immune-related adverse events, physicians should document the immunological characteristics of atypical skin toxicities. Moreover, the kinetics of induced autoantibodies could provide a proxy measure of anti-PD-1 activity after treatment disruption.