bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing Colorectal Cancer: The General Practitioner’s Roles
Authors: Hanks Heather , Veitch Craig , Harris Mark
Published: April 2018

Colorectal cancer (CRC) contributes significantly to the morbidity and mortality of Australians. The introduction of the National Bowel Cancer Screening Project (NBCSP) has focused attention on the role of the general practitioner (GP) in screening for CRC. However, the role of the GP post-diagnosis has not been well-documented in Australia. This study aimed to identify and compare the roles of GPs in CRC management in Australia. Fifteen GPs practising in urban, rural and remote north Queensland were interviewed to explore self-reported roles in CRC management. All GPs reported having a role in diagnosis, referral, follow-up and palliative care. Treatment was provided by remote GPs only. GPs also reported acting as an advocate for their patient, providing post-operative care and co-ordinating care. Their care was influenced by the geographical location of their practice and also their relationship with the specialist. GPs with the strongest relationships with the specialist felt most confident in providing care for their patients and were able to ensure rapid referrals. The role of the GP in CRC management is substantial regardless of location. Improvements in the relationships between GPs and specialists could lead to better communication and greater shared care opportunities.
Dementia Diagnosis: A Pilot Randomised Controlled Trial of Education and IT Audit to Assess Change in GP Dementia Documentation
Authors: Millard Fiona B. , Thistlethwaite Jill , Baune Bernhard T. , Kennedy R. Lee , Spagnolo Chris
Published: April 2018

This trial aimed to test whether education and audit can change documentation of dementia by general practitioners (GPs). We measured the number of new dementia diagnoses documented and Mini Mental State Examinations (MMSEs) performed following the interventions of education and audit, using electronic data for audit and outcomes. GPs in Mackay were randomly assigned to the interventions of either an educational workshop or education combined with audit of their documented dementia diagnoses and MMSE performed in electronic medical records. The results were compared with a control group of GPs in Townsville. Together with education, audit significantly improved documentation of dementia compared with education alone and a control group. We developed a data extraction tool for Medical Director (MD) software producing a report of dementia diagnoses, MMSE tests and practice population at risk of dementia. General practitioners participating in this project were likely to be motivated to learn about dementia. Education using Royal Australian College of General Practitioners? (RACGP) guidelines and audit using an IT extraction tool can improve computer documentation of dementia. Differences in practice software and past adverse experiences with new software were barriers to using our data extraction software for audit purposes.
Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia
Authors: Fan Yi , Liu Weiqing , Bi Ruiye , Densmore Michael J. , Sato Tadatoshi , Mannstadt Michael , Yuan Quan , Zhou Xuedong , Olauson Hannes , Larsson Tobias E. , Toka Hakan R. , Pollak Martin R. , Brown Edward M. , Lanske Beate
Published: April 2018

Significance

Secondary hyperparathyroidism (SHPT) is a severe consequence of chronic kidney disease. A better understanding of the mechanisms controlling the progression of SHPT and the regulation of parathyroid hormone (PTH) production is clinically relevant. Utilizing parathyroid gland (PTG)-specific knockout mouse models, we demonstrated calcium-sensing receptor (CaSR) and Klotho together regulate PTH synthesis and PTG growth, and that Klotho contributes to PTH suppression in the absence of CaSR. Klotho exerts an independent function in mediating PTH secretion under chronic hypocalcemia and in suppressing PTG cell proliferation. Moreover, the results revealed a previously unidentified interaction between PTG-expressed CaSR and Klotho. These findings highlight the essential and interrelated roles for CaSR and Klotho to prevent parathyroid hyperplasia, suggesting potential treatment strategies to control PTH synthesis and hyperparathyroidism.
Cell contraction induces long-ranged stress stiffening in the extracellular matrix
Authors: Han Yu Long , Ronceray Pierre , Xu Guoqiang , Malandrino Andrea , Kamm Roger D. , Lenz Martin , Broedersz Chase P. , Guo Ming
Published: April 2018

Significance

The behavior of cells is strongly affected by the mechanics of their surroundings. In tissues, cells interact with the extracellular matrix, a 3D network of biopolymers with a highly nonlinear elastic response. We introduce a method exploiting this matrix nonlinearity to infer mechanical stresses in 3D. Using this method, we demonstrate that cell contractility induces large stresses, which generate a massive stiffness gradient over an extended region in 3D matrices of collagen, fibrin, and Matrigel. Our work highlights the importance of nonlinear matrix mechanics at the microscopic scale and suggests a concrete mechanism through which cells can control their microenvironment and mechanically communicate with each other.
Place Names and Enregistered Identity of Michigan’s Upper Peninsula
Authors: Adams Michael
Published: April 2018

A clever reward system for frequent catalogue shoppers of Zingerman’s – a renowned delicatessen in Ann Arbor, Michigan – uses Michigan place names to indicate spending and reward levels. In favoring those of Michigan’s Upper Peninsula (UP), the item participates in the process of enregistering UP dialect.
Bending deformation and fracture characterisation in quenching and partitioning steel
Authors: Yang Yong-Gang , Mi Zhen-Li , Xu Mei , Jiang Hai-Tao , Xiu Qi
Published: April 2018

The bending deformation recorded and fracture characterisation seen during the process of quenching and partitioning (Q&P) steel are investigated as a function of bending angle. According to experimental results, the mechanically induced martensitic transformation of the retained austenite occurred heterogeneously in the direction of thickness. Results from electron backscattered diffraction and finite element analysis confirmed that the heterogeneous phase transformation was caused by the stress difference in the direction of thickness. The results prove fracture behaviour is dominated by martensite cracking. The results provide a new insight into deformation characterisation of the Q&P steel under bending, which allows the design and optimisation of mechanical properties.
Axial to transverse energy mixing dynamics in octupole-based magnetostatic antihydrogen traps
Authors: Zhong A , Fajans J , Zukor A F
Published: April 2018

The nature of the trajectories of antihydrogen atoms confined in an octupole minimum-B trap is of great importance for upcoming spectroscopy, cooling, and gravity experiments. Of particular interest is the mixing time between the axial and transverse energies for the antiatoms. Here, using computer simulations, we establish that almost all trajectories are chaotic, and then quantify the characteristic mixing time between the axial and transverse energies. We find that there are two classes of trajectories: for trajectories whose axial energy is higher than about 20% of the total energy, the axial energy substantially mixes within about 10 s, whereas for trajectories whose axial energy is lower than about 10% of the total energy, the axial energy remains nearly constant for 1000 s or longer.
Counting zeros in quaternion algebras using Jacobi forms
Authors: Boylan Hati̇ce , Skoruppa Nils-Peter , Zhou Haigang
Published: April 2018

We use the theory of Jacobi forms to study the number of elements in a maximal order of a definite quaternion algebra over the field of rational numbers whose characteristic polynomial equals a given polynomial. A certain weighted average of such numbers equals (up to some trivial factors) the Hurwitz class number

H
(
4
n
−

r
2

)

H(4n-r^2)

. As a consequence we obtain new proofs for Eichler’s trace formula and for formulas for the class and type number of definite quaternion algebras. As a secondary result we derive explicit formulas for Jacobi Eisenstein series of weight 

2
2

on

Γ
0

(
N
)

\Gamma _0(N)

and for the action of Hecke operators on Jacobi theta series associated to maximal orders of definite quaternion algebras.
SnapperDB: a database solution for routine sequencing analysis of bacterial isolates
Authors: Dallman Timothy , Ashton Philip , Schafer Ulf , Jironkin Aleksey , Painset Anais , Shaaban Sharif , Hartman Hassan , Myers Richard , Underwood Anthony , Jenkins Claire , Grant Kathie
Published: April 2018

Real-time surveillance of infectious disease using whole genome sequencing data poses challenges in both result generation and communication. SnapperDB represents a set of tools to store bacterial variant data and facilitate reproducible and scalable analysis of bacterial populations. We also introduce the ‘SNP address’ nomenclature to describe the relationship between isolates in a population to the single nucleotide resolution. We announce the release of SnapperDB v1.0 a program for scalable routine SNP analysis and storage of microbial populations.

Availability and implementation

SnapperDB is implemented as a python application under the open source BSD license. All code and user guides are available at https://github.com/phe-bioinformatics/snapperdb. Reference genomes and SnapperDB configs are available at https://github.com/phe-bioinformatics/snapperdb_references.
A sequence family database built on ECOD structural domains
Authors: Liao Yuxing , Schaeffer R Dustin , Pei Jimin , Grishin Nick V
Published: April 2018

Motivation

The ECOD database classifies protein domains based on their evolutionary relationships, considering both remote and close homology. The family group in ECOD provides classification of domains that are closely related to each other based on sequence similarity. Due to different perspectives on domain definition, direct application of existing sequence domain databases, such as Pfam, to ECOD struggles with several shortcomings.

Results

We created multiple sequence alignments and profiles from ECOD domains with the help of structural information in alignment building and boundary delineation. We validated the alignment quality by scoring structure superposition to demonstrate that they are comparable to curated seed alignments in Pfam. Comparison to Pfam and CDD reveals that 27 and 16% of ECOD families are new, but they are also dominated by small families, likely because of the sampling bias from the PDB database. There are 35 and 48% of families whose boundaries are modified comparing to counterparts in Pfam and CDD, respectively.

Availability and implementation

The new families are now integrated in the ECOD website. The aggregate HMMER profile library and alignment are available for download on ECOD website (http://prodata.swmed.edu/ecod).

Supplementary information

Supplementary data are available at Bioinformatics online.
Ribopeaks: a web tool for bacterial classification through m/z data from ribosomal proteins
Authors: Tomachewski Douglas , Galvão Carolina Weigert , de Campos Júnior Arion , Guimarães Alaine Margarete , Ferreira da Rocha José Carlos , Etto Rafael Mazer
Published: April 2018

MALDI-TOF MS is a rapid, sensitive and economic tool for bacterial identification. Highly abundant bacterial proteins are detected by this technique, including ribosomal proteins (r-protein), and the generated mass spectra are compared with a MALDI-TOF MS spectra database. Currently, it allows mainly the classification of clinical bacteria due to the limited number of environmental bacteria included in the spectra database. We present a wide-ranging bacterium classifier tool, called Ribopeaks, which was created based on r-protein data from the Genbank. The Ribopeaks database has more than 28 500 bacterial taxonomic records. It compares the incoming m/z data from MALDI-TOF MS analysis with models stored in the Ribopeaks database created by machine learning and then taxonomically classifies the bacteria.

Availability and implementation

The software is available at http://www.ribopeaks.com.

Supplementary information

Supplementary data are available at Bioinformatics online.
IRscope: an online program to visualize the junction sites of chloroplast genomes
Authors: Amiryousefi Ali , Hyvönen Jaakko , Poczai Peter
Published: April 2018

Motivation

Genome plotting is performed using a wide range of visualizations tools each with emphasis on a different informative dimension of the genome. These tools can provide a deeper insight into the genomic structure of the organism.

Results

Here, we announce a new visualization tool that is specifically designed for chloroplast genomes. It allows the users to depict the genetic architecture of up to ten chloroplast genomes in the vicinity of the sites connecting the inverted repeats to the short and long single copy regions. The software and its dependent libraries are fully coded in R and the reflected plot is scaled up to realistic size of nucleotide base pairs in the vicinity of the junction sites. We introduce a website for easier use of the program and R source code of the software to be used in case of preferences to be changed and integrated into personal pipelines. The input of the program is an annotation GenBank (.gb) file, the accession or GI number of the sequence or a DOGMA output file. The software was tested using over a 100 embryophyte chloroplast genomes and in all cases a reliable output was obtained.

Availability and implementation

Source codes and the online suit available at https://irscope.shinyapps.io/irapp/ or https://github.com/Limpfrog/irscope.
Gross Negligence (Medical) Manslaughter and the Puzzling Implications of Negligent Ignorance: Rose v R [2017] EWCA Crim 1168
Authors: Mullock Alexandra
Published: April 2018

This commentary explores the Court of Appeal’s decision in the case of Rose1 in order to assess the risk of liability for gross negligence manslaughter currently faced by the medical profession in the event that negligence causes the death of a patient. Subtly modifying the test established in Adomako,2Rose confirms that in order to be potentially liable, there must be a serious risk of death that was, rather than ought to have been, obvious/foreseeable to the defendant. Consequently, in more complex cases where the serious risk of death is not immediately obvious, negligently failing to assess risk seems to prevent potential liability on the basis that the putative defendant was in a position of negligent ignorance.
Antifungal susceptibilities, in vitro production of virulence factors and activities of ceragenins against Candida spp. isolated from vulvovaginal candidiasis
Authors: Hacioglu Mayram , Guzel Cagla Bozkurt , Savage Paul B , Tan A Seher Birteksoz
Published: April 2018

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis after bacterial vaginosis, affecting millions of women worldwide every year. Candida albicans is the most frequent agent of VVC followed by other species of Candida such as C. glabrata and C. parapsilosis. Out of a total of 100 clinical isolates of Candida spp. obtained from patients diagnosed with VVC, 84 were identified as C. albicans, while the remaining isolates were identified as non–-albicans Candida strains. Phospholipases and proteinases were produced by a majority of the C. albicans strains and esterases and hemolysins a minority of these strains. Among the non–C. albicans strains, only a few of the strains produced these proteins. Nearly all of the isolates formed biofilms. Our results showed that the butoconazole, clotrimazole, and fluconazole were active against C. albicans and less so against the non–albicans Candida strains. The MIC90 of amphotericin B and nystatins were 2 and 4 μg/ml, respectively, against either C. albicans or non–albicans Candida spp. Representative ceragenins (CSA-13, CSA-131, and CSA-138), developed as mimics of endogenous antimicrobial peptides, were active against fluconazole-resistant strains, both alone and in combination with fluconazole. These results suggest the potential use of ceragenins in treating VVC, including infections caused by fluconazole-resistant isolates.
Circular polarization of gravitational waves from non-rotating supernova cores: a new probe into the pre-explosion hydrodynamics
Authors: Hayama Kazuhiro , Kuroda Takami , Kotake Kei , Takiwaki Tomoya
Published: April 2018

We present an analysis of the circular polarization of gravitational waves (GWs) using results from three-dimensional (3D), general relativistic (GR) core-collapse simulations of a non-rotating 15 M⊙ star. For the signal detection, we perform a coherent network analysis taking into account the four interferometers of LIGO Hanford, LIGO Livingston, VIRGO, and KAGRA. We focus on the Stokes V parameter, which directly characterizes the asymmetry of the GW circular polarization. We find that the amplitude of the GW polarization becomes bigger for our 3D-GR model that exhibits strong activity of the standing accretion shock instability (SASI). Our results suggest that the SASI-induced accretion flows to the proto-neutron star (PNS) lead to a characteristic, low-frequency modulation (100–200 Hz) in both the waveform and the GW circular polarization. By estimating the signal-to-noise ratio of the GW polarization, we demonstrate that the detection horizon of the circular polarization extends by more than a factor of several times farther comparing to that of the GW amplitude. Our results suggest that the GW circular polarization, if detected, could provide a new probe into the pre-explosion hydrodynamics such as the SASI activity and the g-mode oscillation of the PNS.
Aneurysm Size is the Strongest Risk Factor for Intracranial Aneurysm Growth in the Eastern Finnish Population
Authors: Björkman Joel , Frösen Juhana , Tähtinen Olli , Huttunen Terhi , Huttunen Jukka , Kurki Mitja I , von und zu Fraunberg Mikael , Koivisto Timo , Manninen Hannu , Jääskeläinen Juha E , Lindgren Antti E
Published: April 2018

BACKGROUND

Saccular intracranial aneurysm (sIA) growth during follow-up is associated with high risk for subsequent rupture. Finnish patients have been suggested to have higher risk for subarachnoid hemorrhage, but follow-up studies of sIA growth in the Finnish population are scarce.

OBJECTIVE

To identify the strongest risk factors for sIA growth in Eastern Finnish population by studying 205 patients with 350 unruptured sIAs with angiographic follow-up imaging.

METHODS

In this population-based cohort study, we included unruptured sIA patients from the Kuopio University Hospital Intracranial Aneurysm Patient and Family database with at least 6 mo of angiographic follow-up after the diagnosis of sIAs. Angiograms were re-evaluated to detect aneurysms with growth of at least 1.0 mm. Cox regression analysis with patient- and aneurysm-related risk factors was used to calculate hazard ratios with 95% confidence intervals for growth. In addition, we tested the diagnostic value of previously introduced PHASES score for the prediction of sIA growth in Eastern Finnish population.

RESULTS

Of the 350 unruptured aneurysms, 36 (10.3%) showed growth during median follow-up of 1.7 yr and total follow-up of 790 yr. In the multivariate Cox regression analysis, sIA size and location in the middle cerebral artery were significant risk factors for sIA growth. In receiver operator characteristic curves, both PHASES score and sIA size had relatively low areas under the curve.

CONCLUSION

Our study indicates that aneurysm size is the strongest risk factor for aneurysm growth in Eastern Finnish population. Further studies are required to identify new risk factors for aneurysm growth.
Cardiovascular Effects of Hookah Smoking: Potential Implications for Cardiovascular Risk
Authors: Rezk-Hanna Mary , Benowitz Neal L
Published: April 2018

Introduction

Smoking is a major cause of cardiovascular morbidity and mortality worldwide. Hookah (ie, waterpipe) smoking is a centuries-old revived yet understudied global epidemic of tobacco use. Because of the traditional set-up of a hookah-pipe, in addition to inhaling tobacco-combustion products, smokers are also exposed to large amounts of charcoal combustion products from the burning charcoal briquettes used to heat the hookah flavored tobacco. Despite being heavily advertised and actively glamorized in the mass media as a healthier tobacco alternative, the toxicological constituents of hookah smoke—including nicotine, carbon monoxide, particulates, oxidants, heavy metals, phenols and flavorants—indicate the potential to cause adverse cardiovascular events.

Methods

Herein, we review evidence on hookah smoke toxicological constituents, cardiovascular effects and potential mechanisms by which hookah smoke aerosol could cause cardiovascular disease.

Results

The evidence reviewed here indicates that contrary to the widespread popular belief that hookah is a healthier tobacco alternative, the constituents of hookah smoke aerosol contains similar chemicals compared to cigarette smoke, many of which are known to be harmful to cardiovascular health and mediated by similar pathophysiologic processes. Because the burning charcoal briquettes are a unique source of toxicant emissions specific to hookah smoking, some constituents differ in their quantities from cigarettes with some of their cardiovascular effects unknown.

Conclusions

To date, much more is known about the constituents and their toxicology than about the effects of hookah smoking on human cardiovascular health. Further research on long-term consequences of hookah use is needed.

Implications

This review provides an overview on the potential impact of hookah smoking on cardiovascular health. Readers will gain an insight into evidence on its toxicological constituents, human health effects, and pathophysiological mechanisms by which hookah smoking might cause cardiovascular disease. The review also highlights current research gaps regarding the cardiovascular consequences of hookah smoking, specifically the long-term consequences in the United States and Europe among flavored-hookah tobacco users.
Beyond the Lamppost: A Proposal for a Fourth Wave of Education for Collaboration
Authors: Paradis Elise , Whitehead Cynthia R.
Published: April 2018

Interprofessional education (IPE) is an increasingly popular educational model that aims to educate health care students to be better collaborators by enabling them to learn with, from, and about each other. IPE’s rising popularity is evident in the increase in scholarship on this topic over the last few decades. In this Perspective, the authors briefly describe three historical “waves” of IPE: managing the health workforce through shared curriculum, maximizing population health through health workforce planning, and fixing individuals to fix health care. Using insights from the social sciences and past practice, they then discuss six reasons why the current third wave of IPE is likely to fall short of meeting its goals, including that (1) IPE is logistically complex and costly, (2) IPE is developmentally inappropriate, (3) the link between IPE and key outcomes is still missing, (4) IPE insufficiently engages with theory, (5) IPE rarely addresses power and conflict, and (6) health care is an inertial system that IPE is unlikely to change. The authors conclude by sharing their vision for a fourth wave of education for collaboration, addressing workplace systems and structures, which would combine undergraduate, uniprofessional education for collaboration with practice-based interventions.
Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy
Authors: Gruenbaum Shaun E. , Dhaher Roni , Rapuano Amedeo , Zaveri Hitten P. , Tang Amber , de Lanerolle Nihal , Eid Tore
Published: April 2018

Background:

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood.

Materials and Methods:

Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis.

Results:

Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls.

Conclusions:

Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans.
Reported Side-effects and Safety Considerations for the Use of Blood Flow Restriction During Exercise in Practice and Research
Authors: Brandner Christopher R. , May Anthony K. , Clarkson Matthew J. , Warmington Stuart A.
Published: April 2018

Blood flow restriction (BFR) exercise is seen as a potential alternative to traditional training methods, and evidence suggests this is being used with both healthy and clinical populations worldwide. Although the efficacy of the technique regarding muscular adaptations is well known, the safety of its use has been questioned. The purpose of this review was: (i) provide an overview of the known reported side-effects while using BFR exercise; (ii) highlight risks associated with the cardiovascular system, and; (iii) suggest recommendations to minimize risk of complications in both healthy and clinical populations. Overall, reported side-effects include perceptual type responses (ie, fainting, numbness, pain, and discomfort), delayed onset muscle soreness, and muscle damage. There may be heightened risk to the cardiovascular system, in particular increased blood pressure responses, thrombolytic events, and damage to the vasculature. However, while these may be of some concern there is no evidence to suggest that BFR exercise elevates the risk of complications any more than traditional exercise modes. Several modifiable extrinsic factors for risk minimization include selecting the appropriate BFR pressure and cuff width, as well as completion of a preexercise safety standard questionnaire to determine any contraindications to BFR or indeed the prescribed exercise. On the basis of the available evidence, we are confident that the side-effects of using BFR are minimal, and further minimized by the use of an appropriate method of application in the hands of a trained practitioner.
Comparative Usefulness of Sepsis-3, Burn Sepsis, and Conventional Sepsis Criteria in Patients With Major Burns
Authors: Yoon Jaechul , Kym Dohern , Hur Jun , Kim Youngmin , Yang Hyeong-Tae , Yim Haejun , Cho Yong Suk , Chun Wook
Published: April 2018

Objectives:

We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis.

Design:

This was retrospective cohort study.

Setting:

The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea.

Patients:

A total of 1,185 adult patients (mean age, 49.1 yr) were admitted between January 2009 and December 2015.

Interventions:

The 1,185 patients enrolled in the present study and were then re-evaluated based on S1, burn sepsis, and S3 criteria, following which 565 patients, 812 patients, and 809 patients were diagnosed with sepsis based on S1, burn sepsis, S3 criteria, respectively.

Measurements and Main Results:

For diagnostic performance, sensitivity, specificity, predictive value, and likelihood ratio were calculated. The area under the curve of the receiver operating characteristic curve was calculated to determine the accuracy of mortality prediction. The optimal cutoff value of Sequential Organ Failure Assessment score was calculated by the decision tree method. Total body surface area burned was 33.4%. Patients were identified with sepsis using S1 (812), S3 (809), and burn sepsis (565) criteria. Overall mortality was 20.3%, highest (82.2%) and lowest (26.5%) occurred with new septic shock (SH3) and S3, respectively. The sensitivity and specificity for burn sepsis (84.6% and 61.8%) and SH3 (63.1% and 96.5%) were reported. Area under the curve values for Sequential Organ Failure Assessment scores were the highest in all sepsis categories. With Sequential Organ Failure Assessment score greater than or equal to 6 (with infection), the accuracy was 0.86 (95% CI, 0.82–0.89).

Conclusions:

The S3 criteria failed to show superior prognostic accuracy for mortality in severely burned patients. Sequential Organ Failure Assessment score greater than or equal to 6 may be a better criterion for the diagnosis of sepsis in burns patients.
Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes*
Authors: Uber Amy J. , Perman Sarah M. , Cocchi Michael N. , Patel Parth V. , Ganley Sarah E. , Portmann Jocelyn M. , Donnino Michael W. , Grossestreuer Anne V.
Published: April 2018

Objectives:

Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes.

Design:

Retrospective cohort study.

Setting:

Urban tertiary-care hospital.

Patients:

Successfully resuscitated targeted temperature management–treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C.

Interventions:

None.

Measurements and Main Results:

Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation (“heat units”) was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3–5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6–21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0–33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5–4.0 hr] vs median, 3.6 hr [interquartile range, 2.0–5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1–2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6–20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5–33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5–3.8 hr] vs median, 3.6 hr [interquartile range, 2.0–5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the relationship between outcomes and time to Ttarget was no longer significant. Controlling for location, witnessed arrest, age, initial rhythm, and neuromuscular blockade use, increased heat generation was associated with better neurologic (adjusted odds ratio, 1.01 [95% CI, 1.00–1.03]; p = 0.039) and survival (adjusted odds ratio, 1.01 [95% CI, 1.00–1.03]; p = 0.045) outcomes.

Conclusions:

Increased heat generation during targeted temperature management initiation is associated with better outcomes at hospital discharge and may affect the relationship between time to Ttarget and outcomes.
Longer-Term Effectiveness and Tolerability of Adjunctive Open Lurasidone in Patients With Bipolar Disorder
Authors: Miller Shefali , Do Dennis , Gershon Anda , Wang Po W. , Hooshmand Farnaz , Chang Lauren S. , Ketter Terence A.
Published: April 2018

Purpose

To retrospectively assess lurasidone effectiveness/efficacy/tolerability in bipolar disorder (BD) patients.

Methods

Outpatients assessed with Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation received naturalistically administered (primarily adjunctive) open lurasidone while monitored at visits with the Systematic Treatment Enhancement Program for BD Clinical Monitoring Form.

Results

Sixty-one patients (32 type I, 26 type II, 3 type not otherwise specified; mean ± SD age, 45.1 ± 14.0 years; 63.9% were female) received lurasidone with 3.1 ± 1.4 (≥2 in 88.5%, monotherapy in only 3.3%) other nonanxiolytic/hypnotic prescription psychotropics, started during syndromal depression in 57.4%, subsyndromal depression in 23.0%, and euthymia in 19.7%. Lurasidone was taken for median 126 days, with final dose 55.6 ± 30.8 mg/d. By final visit taking lurasidone, syndromal depression rate decreased by nearly one-half to 31.1%, and euthymia rate more than doubled to 42.6%, whereas subsyndromal depression rate was unchanged at 23.0%. Clinical Global Impressions–BD-Overall Severity improved significantly only in patients with baseline syndromal depression. Seventy-seven percent of patients discontinued lurasidone after median 103 days, because of adverse events in 54.1% (most often akathisia, sedation/somnolence, nausea, and weight gain), inefficacy in 16.4%, and other reasons in 6.6%; 12.1% had equal to or greater than 7% weight gain, and 3.3% developed hypomania. Limitations to this study were the open design and demographically homogeneous (relatively affluent, predominantly white female) small sample taking complex pharmacotherapy.

Conclusions

In American specialty clinic BD outpatients, adjunctive longer-term lurasidone commonly relieved syndromal depression and maintained euthymia, suggesting possible effectiveness/efficacy. However, lurasidone was discontinued in 54.1% because of adverse events, suggesting tolerability limitations in these challenging patients, nearly 90% of whom were already taking at least 2 other nonanxiolytic/hypnotic prescription psychotropics.
Comedication of Valproic Acid Is Associated With Increased Metabolism of Clozapine
Authors: Hommers Leif , Scharl Magdalena , Hefner Gudrun , Hohner Matthias , Fischer Matthias , Pfuhlmann Bruno , Deckert Jürgen , Unterecker Stefan
Published: April 2018

Objectives

Valproic acid and clozapine are drugs commonly used in the treatment of schizophrenic and schizoaffective disorders. Pharmacokinetic interactions of valproic acid with several drugs are well known, yet results concerning the interaction with clozapine are inconsistent.

Methods

Steady-state dose-corrected serum concentrations of clozapine and its main metabolite norclozapine were retrospectively analyzed in 45 patients receiving both clozapine and valproic acid. Controls were matched for sex, age, smoking, comedication, and inflammatory response.

Results

The group receiving comedication with valproic acid showed significantly lower median dose-corrected serum concentrations of norclozapine (0.44 [0.27–0.58] (ng/mL)/(mg/d) vs 0.78 [0.60–1.07] (ng/mL)/(mg/d)) as well as metabolite to parent compound ratios (0.40 [0.36–0.47] vs 0.71 [0.58–0.84]) by approximately 44%. Dose-corrected serum concentrations of clozapine were not significantly lower. The effect of valproic acid was independent of sex and smoking.

Conclusions

Comedication with valproic acid accelerated metabolism of clozapine with predominant effects on the degradation of norclozapine. Therapeutic drug monitoring should be applied to guide individual patient responses upon initiation of comedication.
Facilitators and Barriers to the Implementation of iSPRINT: A Sport Injury Prevention Program in Junior High Schools
Authors: Richmond Sarah A. , Donaldson Alex , Macpherson Alison , Bridel William , van den Berg Carla , Finch Caroline F. , Hagel Brent , Emery Carolyn A.
Published: April 2018

Objectives:

Sport injury is the leading cause of hospitalization in Canadian youth and represents a high burden to the health care system. This study aims to describe the facilitators and barriers to implementation of a sport injury prevention program in junior high school physical education (known as iSPRINT), previously shown to reduce the risk of sport-related injury in youth (age, 11-15 years).

Methods:

Focus group data were mapped onto constructs from the Consolidated Framework for Implementation Research (CFIR). Four schools that implemented iSPRINT participated in this study. Forty-seven key stakeholders (teachers, students, principals) participated in 9 semistructured focus groups and 4 interviews. The CFIR was used to guide the focus group discussions, data coding, and analysis using a qualitative content analysis approach.

Results:

Of the 22 applicable CFIR constructs, 16 were identified in the transcripts. The most significant facilitators to successful implementation efforts included evidence strength and quality, adaptability, implementation climate, culture, and having a high level of compatibility facilitated successful implementation efforts. Barriers to implementation included intervention complexity, planning, and readiness for implementation. Constructs that acted as both a facilitator and a barrier, depending on the context, were self-efficacy, execution, and individual identification with the organization.

Conclusions:

Participants in this study reported positive attitudes about implementing iSPRINT, citing evidence strength, adaptability, and constructs related to the organizational setting that contributed to successful implementation. Potential improvements include modifying certain program components, decreasing the number of components, and reducing the equipment required.
Cardiac output monitoring: how to choose the optimal method for the individual patient
Authors: Saugel Bernd , Vincent Jean-Louis
Published: April 2018

Purpose of review

To review the different methods available for the assessment of cardiac output (CO) and describe their specific indications in intensive care and perioperative medicine.

Recent findings

In critically ill patients, persistent circulatory shock after initial resuscitation is an indication for the assessment of CO to monitor the response to fluids and vasoactive agents. In patients with circulatory shock associated with right ventricular dysfunction, pulmonary artery hypertension, or acute respiratory distress syndrome, invasive CO monitoring using indicator dilution methods is indicated. Calibrated and uncalibrated pulse wave analysis enable absolute or relative CO changes to be monitored in real-time during the assessment of fluid responsiveness. In patients undergoing open-heart and thoracic aortic surgery, transesophageal echocardiography is recommended. In selected cardiac surgery patients, advanced hemodynamic monitoring using thermodilution methods can be considered. In high-risk noncardiac surgical patients, invasive pulse wave analysis or esophageal Doppler should be used for perioperative hemodynamic management.

Various invasive, minimally invasive, and noninvasive methods to assess CO are available. A profound understanding of the different CO monitoring methods is key to define indications for CO monitoring in the individual critically ill or surgical patient.
Hepatitis B virus reactivation in patients with resolved hepatitis B virus infection receiving chemotherapy or immunosuppressive therapy
Authors: Su Yi-Chia , Lin Pei-Chin , Yu Hsien-Chung , Wu Chih-Chien
Published: April 2018

Background

The role of antiviral prophylaxis before chemotherapy or immunosuppressive therapy to prevent hepatitis B virus (HBV) reactivation in patients with resolved HBV infection [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc) positive] is unclear. This study aimed to evaluate the efficacy of prophylactic antiviral therapy and outcomes of HBsAg-negative, anti-HBc-positive patients who received chemotherapy or immunosuppressive therapy.

Patients and methods

We retrospectively evaluated the medical records of HBsAg-negative, anti-HBc-positive patients who underwent chemotherapy or immunosuppressive therapy from January 2013 through November 2016 at a single institute in southern Taiwan.

Results

Among 1000 included HBsAg-negative, anti-HBc-positive patients, the rate of hepatitis B surface antibody (anti-HBs) seropositivity before chemotherapy or immunosuppressive therapy was 76.6%. Twenty-six patients received a prophylactic oral antiviral agent (one telbuvudine, two lamivudine, 22 entecavir, and one tenofovir). Seven (0.7%) patients were diagnosed with HBV reactivation during or after chemotherapy courses. In multivariate Cox regression analysis, an rituximab-based regimen (hazard ratio: 11.74; 95% confidence interval: 1.62–84.94; P=0.02) and baseline anti-HBs-positive status (hazard ratio: 0.17; 95% confidence interval: 0.04–0.8; P=0.03) were significant predictive factors for HBV reactivation. Among anti-HBs-negative recipients of rituximab-based chemotherapy, HBV reactivation was observed in zero of nine patients who received prophylactic antiviral therapy and three (33.3%) of nine patients who did not.

Conclusion

Negative anti-HBs status and rituximab-containing regimens are both important factors for predicting chemotherapy or immunosuppressive therapy-related HBV reactivation in patients with resolved HBV infection. Therefore, antiviral prophylaxis should be considered in this patient population.
X-Linked Severe Combined Immunodeficiency and Hepatoblastoma: A Case Report and Review of Literature
Authors: Diaz-Parra Sandra , Lozano-Sanchez Gema , Escobosa-Sanchez Olga , Moreno-Perez David , Morales-Martinez Antonio , Armengol-Niell Carolina , Acha-Garcia Tomás
Published: April 2018

Severe combined immunodeficiency is an inherited disease with profoundly defective T cells, B cells, and natural killer cells. X-linked severe combined immunodeficiency is the most common form. In this report, we describe a 4-month-old male infant who was admitted to our hospital with progressive breathlessness and abdominal mass. He was diagnosed with hepatoblastoma and presented a pneumocystis jirovecii pneumonia at the beginning of chemotherapy. Definitive diagnosis of X-linked severe combined immunodeficiency was established by DNA analysis of the interleukin 2 receptor gamma chain gene. This case is the first report which describes an X-linked severe combined immunodeficiency patient with hepatoblastoma.
GATA2 Deficiency Due to de Novo Complete Monoallelic Deletion in an Adolescent With Myelodysplasia
Authors: Vinh Donald C. , Palma Laura , Storring John , Foulkes William D.
Published: April 2018

GATA2 deficiency is an inherited bone marrow failure syndrome that can manifest with myelodysplasia (myelodysplastic syndrome) with chromosomal aberrations and high risk of evolution to leukemia (particularly, acute myeloid leukemia); immunodeficiency with opportunistic infections; and/or lymphedema. It can be transmitted in families in autosomal-dominant fashion, or present de novo as sporadic disease in adults or children. The authors report a case of an adolescent male with features of GATA2 deficiency resulting from a complete monoallelic deletion, review chromosomal anomalies associated with this disorder, and discuss the management implications.
EBV-PTLD, Adenovirus, and CMV in Pediatric Allogeneic Transplants With Alemtuzumab as Part of Pretransplant Conditioning: A Retrospective Single Center Study
Authors: Cupit-Link Margaret C. , Nageswara Rao Amulya , Warad Deepti M. , Rodriguez Vilmarie , Khan Shakila
Published: April 2018

The risk of viral infections and reactivation occurring in the setting of pediatric allogeneic hematopoietic stem cell transplantation is a concern in the pediatric patient, especially with the use of Alemtuzumab (Campath) as a conditioning agent. The purpose of this study was to determine the incidence of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV-PTLD), cytomegalovirus (CMV), and adenovirus among pediatric recipients of alemtuzumab at our institution. We found that EBV-PTLD occurred in 2.1% of transplants (1 matched unrelated donor [MUD] recipient), CMV reactivation occurred in 12.5% of transplants (4 MUD and 2 matched related donor [MRD] recipients) with disseminated CMV in 2.1% of cases (1 MRD recipient), and adenovirus infection occurred in 8.3% of the total transplants (2 MUD and 2 MRD recipients). Alemtuzumab continues to be used as a method of graft-versus-host disease and graft failure prevention among pediatric recipients of hematopoietic stem cell transplantation and seems to be safer than previously reported. At our institution, alemtuzumab has not increased the risk for EBV-PTLD, CMV infection, or adenovirus.
Triptorelin for Fertility Preservation in Adolescents Treated With Chemotherapy for Cancer
Authors: Meli Mariaclaudia , Caruso-Nicoletti Manuela , La Spina Milena , Nigro Luca Lo , Samperi Piera , D’Amico Salvatore , Bellia Francesco , Miraglia Vito , Licciardello Maria , Cannata Emanuela , Marino Silvia , Cimino Carla , Puglisi Federica , Valvo Laura Lo , Pezzulla Agnese , Russo Giovanna , Di Cataldo Andrea
Published: April 2018

Background:

Triptorelin, a gonadotropin releasing hormone analogue, can be administered to postpubertal female individuals with cancer who receive chemotherapy to obtain menstrual suppression and decrease the risk of hemorrhage caused by thrombocytopenia. Our goal was to assess whether triptorelin also has a protective role against the gonadotoxicity of chemotherapy.

Patients and Methods:

This retrospective observational study includes all postmenarchal female patients who presented to our Unit from 2000 to 2015 and received chemotherapy for cancer. They were administered depot triptorelin. We evaluated long-term ovarian function in order to detect clinical signs of ovarian damage, miscarriages, and pregnancies. Laboratory follow-up consisted in dosing serum follicle stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone. Ultrasound of the ovaries was performed as well.

Results:

Of 36 evaluable patients, 9 received hematopoietic stem cell transplantation (HSCT). The remaining 27 patients maintained normal ovarian function at clinical, laboratory, and ultrasound assessment. Five of them achieved spontaneous physiological pregnancy. Four of the 9 patients who underwent HSCT developed premature ovarian failure.

Conclusion:

Our study suggests that gonadotropin releasing hormone-a administered during chemotherapy can prevent premature ovarian failure in patients treated without HSCT and that it is not enough to preserve the ovarian function during HSCT. Hence, a prospective randomized trial with a larger population would be recommended.