bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposal of a management system to develop an animal welfare strategy for the animal food chain.
Authors: Souza A. P. de O. , Molento C. F. M.
Published: April 2018

This study aimed to propose general guidelines for an animal welfare (AW) management system based on the hazard analysis and critical control point (HACCP) to develop an AW strategy appropriate for individual organizations of the animal food chain. Main adaptations for steps within pre-hazard analysis included a description of the animal species and its intended use, the development of a flow diagram detailing operations where live animals are handled and focusing on animal handling procedures for each stage of animal production or process step. The hazard analysis step included considerations of all kinds of welfare problems that may occur in each step or production stage listed in the flow diagram. Hazard duration, including duration of its consequences, were added to the hazard characterization step. Main changes on establishing critical limits for critical control points included a proposal to set initial thresholds for animal-based measures while scientific-validated data are obtained. Corrective actions considered the concept of implementing real-time procedures to avoid animal suffering, as well as the possibility of reducing identified hazards for future animals. By implementing the HACCP-based system, companies will be prompted to reduce levels of identified AW problems, with potential for mid to long-term reduction of AW problems through planned corrective and preventive actions. Application of the management system may take broader AW discussions to higher corporate levels in companies, needed for the development of an AW strategy, and may promote transparency of processes in animal production, which will benefit both animals and society.
Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells
Authors: Gao Fengyi , Li Guoping , Liu Chao , Gao Hui , Wang Hao , Liu Weixiao , Chen Min , Shang Yongliang , Wang Lina , Shi Jian , Xia Wenlong , Jiao Jianwei , Gao Fei , Li Jian , Chen Liang , Li Wei
Published: April 2018

Testosterone is indispensable for sexual development and maintaining male characteristics, and deficiency of this hormone results in primary or late-onset hypogonadism (LOH). Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell–specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH. The decline in testosterone was caused mainly by a defect in cholesterol uptake in autophagy-deficient Leydig cells. Further studies revealed that once autophagic flux was disrupted, Na+/H+ exchanger regulatory factor 2 (NHERF2) accumulated in Leydig cells, resulting in the down-regulation of scavenger receptor class B, type I (SR-BI) and eventually leading to insufficient cholesterol supply. Collectively, these results reveal that autophagy promotes cholesterol uptake into Leydig cells by eliminating NHERF2, suggesting that dysfunction of autophagy might be causal in the loss of testosterone production in some patients.
Numerical evidences of universal trap-like aging dynamics
Authors: Cammarota Chiara , Marinari Enzo
Published: April 2018

Trap models have been initially proposed as toy models for dynamical relaxation in extremely simplified rough potential energy landscapes. Their importance has recently grown considerably thanks to the discovery that the trap-like aging mechanism directly controls the out-of-equilibrium relaxation processes of more sophisticated spin models, that are considered as the solvable counterpart of real disordered systems. Further establishing the connection between these spin models, out-of-equilibrium behavior and the trap like aging mechanism could shed new light on the properties, which are still largely mysterious, for the activated out-of-equilibrium dynamics of disordered systems. In this work we discuss numerical evidence based on the computations of the permanence times of an emergent trap-like aging behavior in a variety of very simple disordered models—developed from the trap model paradigm. Our numerical results are backed by analytic derivations and heuristic discussions. Such exploration reveals some of the tricks needed to reveal the trap behavior in spite of the occurrence of secondary processes, of the existence of dynamical correlations and of strong finite system’s size effects.
Structure Optimization of Porous Dental Implant Based on 3D Printing
Authors: Ji Fangqiu , Zhang Chunyu , Chen Xianshuai
Published: April 2018

In this paper, selective laser melting (SLM) technology is used to process complex structures. In combination with the theory of biomedicine, a porous implant with a porous structure is designed to induce bone cell growth. The mechanical strength advantage of SLM was discussed by observing the metallographic structure of SLM specimen with mechanical microscope and mechanical tensile test. The osseointegration of porous implants was observed and analyzed by biological experiments. By establishing a mechanical model, the mechanical properties of the bone implant combined with the jaw bone were studied by the simple mechanical analysis under static multi loading and the finite element mechanical analysis. According to the experimental observation and mechanical research, the optimization suggestions for the structure design of the implant made by SLM technology were put forward.
Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-Hypertensive Community-Based Population
Authors: Tanaka Kentaro , Tanaka Fumitaka , Onoda Toshiyuki , Tanno Kozo , Ohsawa Masaki , Sakata Kiyomi , Omama Shinichi , Ogasawara Kuniaki , Ishibashi Yasuhiro , Itai Kazuyoshi , Kuribayashi Toru , Okayama Akira , Nakamura Motoyuki ,   Iwate-Kenco Study Group
Published: April 2018

BACKGROUND

The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals.

METHODS

A total of 4,927 non-hypertensive individuals ≥40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP).

RESULTS

During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, P < 0.001) compared to those with no ECG-LVH. This association was also significant in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic blood pressure (BP) <120 mm Hg and diastolic BP <80 mm Hg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17–0.22, each P value < 0.010).

CONCLUSIONS

In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.
A comprehensive web tool for toehold switch design
Authors: To Andrew Ching-Yuet , Chu David Ho-Ting , Wang Angela Ruoning , Li Frances Cheuk-Yau , Chiu Alan Wai-On , Gao Daisy Yuwei , Choi Chung Hang Jonathan , Kong Siu-Kai , Chan Ting-Fung , Chan King-Ming , Yip Kevin Y
Published: April 2018

Motivation

Toehold switches are a class of RNAs with a hairpin loop that can be unfolded upon binding a trigger RNA, thereby exposing a ribosome binding site (RBS) and permitting translation of the reporter protein. They have been shown very useful in detecting a variety of targets including RNAs from Zika and Ebola viruses. The base complementation between the toehold switch and the trigger RNA also makes it sensitive to sequence variations. Design of toehold switches involves a series of considerations related to their sequence properties, structures and specificities.

Results

Here we present the first comprehensive web tool for designing toehold switches. We also propose a score for predicting the efficacy of designed toehold switches based on properties learned from ∼180 experimentally tested switches.

Availability and implementation

The toehold switch web tool is available at https://yiplab.cse.cuhk.edu.hk/toehold/.
Psychometric evaluation of the Smartphone for Clinical Work Scale to measure nurses’ use of smartphones for work purposes
Authors: Bautista John Robert , Rosenthal Sonny , Lin Trisha Tsui-Chuan , Theng Yin-Leng
Published: April 2018

Objective

This study reports the development and psychometric evaluation of the Smartphone for Clinical Work Scale (SCWS) to measure nurses’ use of smartphones for work purposes.

Methods

Items were developed based on literature review and a preliminary study. After expert consultations and pilot testing, a 20-item scale was administered in January-June 2017 to 517 staff nurses from 19 tertiary-level general hospitals in Metro Manila, Philippines. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate construct validity. Structural equation modeling (SEM) was used to test the predictive validity of SCWS on perceived work productivity.

Results

EFA results show that 15 out of 20 items loaded on five factors: communication with clinicians via call and text, communication with doctors via instant messaging, information seeking, communication with nurses via instant messaging, and communication with patients via call and text. CFA results suggest that the five factors that form SCWS have adequate fit to the data, thus supporting construct validity. SEM results suggest predictive validity since SCWS was positively associated with perceived work productivity.

Conclusions

The 15-item SCWS showed satisfactory psychometric properties for use in future studies. These studies can focus on identifying factors associated with nurses’ use of smartphones for work purposes.
Affordability and Price Increases of New Cancer Drugs in Clinical Guidelines, 2007–2016
Authors: Hwang Thomas J , Kesselheim Aaron S , Gyawali Bishal
Published: April 2018

In response to the rising cost of cancer drugs, the National Comprehensive Cancer Network (NCCN) recently developed a value framework, known as “Evidence Blocks,” to grade the efficacy, safety, evidence quality, evidence consistency, and affordability of treatments included in its clinical guidelines. The value scores were available for 55 of the 69 new cancer drugs approved by the US Food and Drug Administration from 2007 to 2016. Overall, the treatment costs for 95% of new cancer medicines in NCCN clinical guidelines were scored as “very expensive” or “expensive”. In multivariable ordered logistic regression models, there was no association between the affordability of new cancer drugs and efficacy and safety data available in clinical guidelines. Most guideline-recommended drugs were subject to annual list price increases exceeding inflation.
The cosmic transparency measured with Type Ia supernovae: implications for intergalactic dust
Authors: Goobar Ariel , Dhawan Suhail , Scolnic Daniel
Published: April 2018

Observations of high-redshift Type Ia supernovae (SNe Ia) are used to study the cosmic transparency at optical wavelengths. Assuming a flat Λ cold dark matter (ΛCDM) cosmological model based on baryon acoustic oscillations and cosmic microwave background measurements, redshift dependent deviations of SN Ia distances are used to constrain mechanisms that would dim light. The analysis is based on the most recent Pantheon SN compilation, for which there is a $0.03 \pm 0.01 \, {(\rm {stat})}$ mag discrepancy in the distant supernova distance moduli relative to the ΛCDM model anchored by supernovae at z < 0.05. While there are known systematic uncertainties that combined could explain the observed offset, here we entertain the possibility that the discrepancy may instead be explained by scattering of supernova light in the intergalactic medium (IGM). We focus on two effects: Compton scattering by free electrons and extinction by dust in the IGM. We find that if the discrepancy is entirely due to dimming by dust, the measurements can be modelled with a cosmic dust density $\Omega _{\rm IGM}^{\rm dust} = 8 \times 10^{-5} (1+z)^{-1}$, corresponding to an average attenuation of 2 × 10−5 mag Mpc−1 in V band. Forthcoming SN Ia studies may provide a definitive measurement of the IGM dust properties, while still providing an unbiased estimate of cosmological parameters by introducing additional parameters in the global fits to the observations.
Gradient pattern analysis applied to galaxy morphology
Authors: Rosa R R , de Carvalho R R , Sautter R A , Barchi P H , Stalder D H , Moura T C , Rembold S B , Morell D R F , Ferreira N C
Published: April 2018

Gradient pattern analysis (GPA) is a well-established technique for measuring gradient bilateral asymmetries of a square numerical lattice. This paper introduces an improved version of GPA designed for galaxy morphometry. We show the performance of the new method on a selected sample of 54 896 objects from the SDSS-DR7 in common with Galaxy Zoo 1 catalogue. The results suggest that the second gradient moment, G2, has the potential to dramatically improve over more conventional morphometric parameters. It separates early- from late-type galaxies better (${\sim } 90\hbox{ per cent}$) than the CAS system ($C\sim 79\hbox{ per cent}, A\sim 50\hbox{ per cent}, S\sim 43\hbox{ per cent}$) and a benchmark test shows that it is applicable to hundreds of thousands of galaxies using typical processing systems.
Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study
Authors: Ding Dale , Mehta Gautam U , Patibandla Mohana Rao , Lee Cheng-Chia , Liscak Roman , Kano Hideyuki , Pai Fu-Yuan , Kosak Mikulas , Sisterson Nathaniel D , Martinez-Alvarez Roberto , Martinez-Moreno Nuria , Mathieu David , Grills Inga S , Blas Kevin , Lee Kuei , Cifarelli Christopher P , Katsevman Gennadiy A , Lee John Y K , McShane Brendan , Kondziolka Douglas , Lunsford L Dade , Vance Mary Lee , Sheehan Jason P
Published: April 2018

BACKGROUND

Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined.

OBJECTIVE

To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors.

METHODS

We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo.

RESULTS

The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%.

CONCLUSION

SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.
Novice and Expert Clinical Instructors: A Method to Enhance Teaching Capabilities
Authors: Roman Tammy
Published: April 2018

Due to scarce opportunities for professional development in clinical teaching, an online learning community was developed to provide initial and ongoing education for novice and experienced clinical instructors. Asynchronous learning modules were developed that included discussion boards to share best practices. Results demonstrated a significant change in the participants’ knowledge of clinical teaching as well as the identification of a lack of confidence among novice instructors (p < .05). This research establishes the benefit of a learning community for both new and experienced clinical instructors and the need to increase confidence in their teaching abilities.
Relationship of Ethical Knowledge to Action in Senior Baccalaureate Nursing Students
Authors: Moe Catherine S.
Published: April 2018

It is not known if nursing graduates have skills to manage ethical clinical situations. This study examined the relationship between knowledge of ethics to choices of action in baccalaureate nursing students. It explored individual student characteristics to determine what impact these have on the relationship between knowledge and action. A significant correlation between knowledge of ethics and action was found. College courses on ethics, previous experience in making health care decisions, or general health care experience did not significantly impact this relationship, but the data trended toward significance with previous experience in making decisions and supported a need for further research.
Screening women for intimate partner violence
Authors: Knox Beth
Published: April 2018

Intimate partner violence continues to be a challenge for advanced practice registered nurses to address and manage in their daily practice. This article reviews current healthcare concerns in heterosexual, bisexual, transgender, and lesbian women, and explores screening guidelines and resources for developing successful screening habits. Additionally, the article discusses how the Transtheoretical Model and Stages of Change offers insight into the behavior of women who experience intimate partner violence and provides safety strategies for these women.
Unilateral Lateral Epicondylalgia Shows a Pro-nociceptive Pain Profile
Authors: Bisset Leanne , Carty Michelle , Smith Ashley
Published: April 2018

Objective:

Lateral epicondylalgia (LE, tennis elbow) is characterized by both local tissue pathology and features indicative of secondary hyperalgesia. The aim of this study was to evaluate endogenous pain modulation characteristics in people with chronic LE, and to investigate the relationship between endogenous pain modulation and clinical characteristics.

Materials and Methods:

This case-control observational study included 25 participants with LE of at least 6 weeks’ duration and 15 age-matched (±5 y) healthy control participants, who were each evaluated in a single session. Pain and disability were assessed using the patient-rated tennis elbow evaluation and pain-free grip strength. Endogenous pain modulation was assessed using pressure pain threshold, cold pain threshold, conditioned pain modulation (CPM), and temporal summation (TS).

Results:

The LE group exhibited significantly lower pain-free grip and pressure pain threshold bilaterally compared with the control group. Cold pain threshold was significantly reduced on the affected side compared with the matched control side. There was no significant difference between groups for CPM; however, the LE group exhibited significantly increased facilitation as measured by TS (between-group difference in change score of 9.6 mm on a 0 to 100 mm pain visual analogue scale; 95% confidence intervals, 3.4-15.8 mm). There was no significant correlation between pain modulation and clinical measures of pain and disability.

Discussion:

LE is characterized by locally increased facilitation of pain, as measured by TS, but this is not associated with severity of pain or disability.
Atlas Fractures
Authors: Smith Richard M. , Bhandutia Amit K. , Jauregui Julio J. , Shasti Mark , Ludwig Steven C.
Published: April 2018

Fractures of the C1 vertebrae (atlas) are commonly the result of falls and other trauma, which cause hyperextension, or axial compression of the cervical spine. Although historically thought as a benign injury with lower neurological risks, current data suggests that this may not hold true for geriatric patients (aged 65 y and older) who may be predisposed to these fractures even after lower-energy trauma such as ground-level falls. Advancements in orthopedic trauma care has increased our diagnostic abilities to identify and manage patients with C1 fractures and other upper cervical spine trauma. However, there are no universal treatment guidelines based on level I trials. Current treatment ranges from nonoperative to operative management depending on fracture-pattern and integrity of the surrounding ligaments. Furthermore, in the elderly patients these fractures present a unique dilemma due to preexisting comorbidities and contraindications to various treatment modalities. C1 fractures warrant greater recognition to provide optimal treatment to patients and minimize the risk for developing complications. The goal of this review is to highlight the most updated treatment guidelines and to discuss the complications of both operative and nonoperative management of C1 fractures especially among the elderly patient population.
Total Endoprosthesis Versus Lundborg´s Resection Arthroplasty for the Treatment of Trapeziometacarpal Joint Osteoarthritis
Authors: Erne Holger , Scheiber Claudia , Schmauss Daniel , Loew Steffen , Cerny Michael , Ehrl Denis , Schmauss Verena , Machens Hans-Guenter , Muhl Philipp
Published: April 2018

Background:

There exist various operative approaches for the treatment of trapeziometacarpal joint osteoarthritis. The aim of this study was to compare the results of Lundsborg’s resection arthroplasty (RA) with implantation of a total endoprosthesis.

Patients and Methods:

In this 2-center study, we retrospectively analyzed 71 patients with symptomatic osteoarthritis of the carpometacarpal I joint stage III according to the Eaton-Littler classification. Thirty-two patients underwent a Lundsborg’s RA group, and 39 patients received a total endoprosthesis of the carpometacarpal I joint (TEP group). We evaluated operative time, DASH score, postoperative time until resolution of symptoms, pain level, pinch force, and satisfaction with the treatment.

Results:

Both groups had a similar mean length of follow-up of 42 months (TEP group) and 36 months (RA group). The final DASH score was significantly better in the TEP-group (10.1 versus 21.5 in the RA group; P ≤ 0.05). Also, the time interval from surgery till absence of any pain (1.5 versus 5.9 months) and the time of inability to work (6 versus 21 weeks) were significantly shorter for the TEP group compared with the RA group (P ≤ 0.05). The pinch force, pain intensity, and the satisfaction with the treatment were comparable (P > 0.05). The duration of the operation was significantly shorter in the RA group (31 min versus 65 min in the TEP group; P ≤ 0.05).

Conclusion:

Both techniques resulted in improved function of the operated hand and a clear reduction of symptoms. However, the implantation of a total endoprosthesis seems to have advantages, given a significantly better DASH score and a significantly shorter time until resolution of symptoms.
Clinical Value of Dorsal Medulla Oblongata Involvement Detected With Conventional Magnetic Resonance Imaging for Prediction of Outcome in Children With Enterovirus 71-Related Brainstem Encephalitis
Authors: Liu Kun , Zhou Yongjin , Cui Shihan , Song Jiawen , Ye Peipei , Xiang Wei , Huang Xiaoyan , Chen Yiping , Yan Zhihan , Ye Xinjian
Published: April 2018

Background:

Brainstem encephalitis is the most common neurologic complication after enterovirus 71 infection. The involvement of brainstem, especially the dorsal medulla oblongata, can cause severe sequelae or death in children with enterovirus 71 infection. We aimed to determine the prevalence of dorsal medulla oblongata involvement in children with enterovirus 71-related brainstem encephalitis (EBE) by using conventional magnetic resonance imaging (MRI) and to evaluate the value of dorsal medulla oblongata involvement in outcome prediction.

Methods:

Forty-six children with EBE were enrolled in the study. All subjects underwent a 1.5 Tesla MRI examination of the brain. The disease distribution and clinical data were collected. Dichotomized outcomes (good vs. poor) at longer than 6 months were available for 28 patients. Logistic regression was used to determine whether the MRI-confirmed dorsal medulla oblongata involvement resulted in improved clinical outcome prediction when compared with other location involvement.

Results:

Of the 46 patients, 35 had MRI evidence of dorsal medulla oblongata involvement, 32 had pons involvement, 10 had midbrain involvement and 7 had dentate nuclei involvement. Patients with dorsal medulla oblongata involvement or multiple area involvement were significantly more often in the poor outcome group than in the good outcome group. Logistic regression analysis showed that dorsal medulla oblongata involvement was the most significant single variable in outcome prediction (predictive accuracy, 90.5%), followed by multiple area involvement, age and initial Glasgow Coma Scale score.

Conclusions:

Dorsal medulla oblongata involvement on conventional MRI correlated significantly with poor outcomes in EBE children, improved outcome prediction when compared with other clinical and disease location variables, and was most predictive when combined with multiple area involvement, Glasgow Coma Scale score and age.
Perinatal Risk Factors Associated With Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000–2012): A Record Linkage Cohort Study
Authors: Fathima Parveen , Snelling Thomas Laurence , de Klerk Nicholas , Lehmann Deborah , Blyth Christopher Charles , Waddington Claire Shelley , Moore Hannah Catherine
Published: April 2018

Background:

Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions associated with childhood gastroenteritis-related hospitalizations.

Methods:

We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia 2000–2012. We identified hospital admissions up to <15 years of age pertaining to these children, with a principal diagnosis code for infectious gastroenteritis. Cox regression was used to obtain the adjusted hazard ratios with 95% confidence intervals and the population attributable fractions associated with each risk factor in Aboriginal and non-Aboriginal children for their first gastroenteritis-related hospital admission.

Results:

There were a total of 15,888 gastroenteritis-related hospital admissions (25.7% occurring among non-Aboriginal children). The overall gastroenteritis hospitalization rate for children <15 years of age was 4.6/1000 child-years for non-Aboriginal children and 21.5/1000 child-years for Aboriginal children. Male gender, <20 years of maternal age, preterm birth, low birth weight, residence in remote regions of Western Australia and birth in the pre-rotavirus vaccine era were significant independent risk factors for gastroenteritis hospitalization in both Aboriginal and non-Aboriginal children. Additionally, birth by caesarean section and low socioeconomic status were identified as being associated with gastroenteritis hospitalization in non-Aboriginal children. Population attributable fractions suggest that 39% of all gastroenteritis hospitalizations in non-Aboriginal children (38% in Aboriginal children) could be averted if all children receive the rotavirus vaccine.

Conclusions:

Given the beneficial effect of infant rotavirus vaccination in preventing all-cause gastroenteritis hospitalization, efforts should be taken to optimize rotavirus vaccine coverage in those at highest risk.
Piperacillin-Tazobactam–Induced Neutropenia and Fever
Authors: Al Soub Hussam , Al Madhoun Eyad , Al Maslamani Muna , Al-Khal Abdullatif , Al Soub Deema
Published: April 2018

Background

This study aims to describe our experience with 11 cases of piperacillin-tazobactam–related neutropenia and fever that were observed over a 6-year period and detail some of their clinical findings, risk factors, management, and outcome.

Method

Review of the records of all cases of piperacillin-tazobactam–related neutropenia and fever reported to the adverse drug reaction reporting system of the Department of Pharmacy at Hamad General Hospital in the period between 2010 and 2015 was performed.

Results

During the study period, 11 cases of piperacillin-tazobactam–related neutropenia and fever were identified. Nine were males, and 2 were females, with a mean age of 36 years. All patients had neutropenia, and 10 had fever at the same time. The mean duration of piperacillin-tazobactam use before the development of neutropenia and fever was 17.3 days. Concomitant anemia and thrombocytopenia were observed in 82% and 55%, respectively. Recovery was fast with resolution of fever and neutropenia in 1.5 days and 2.9 days, respectively. All patients survived.

Conclusion

Piperacillin-tazobactam is a commonly used antibiotic in Qatar. Neutropenia and fever related to piperacillin-tazobactam does occur, however, very rarely. The most important risk factor for its occurrence is prolonged use of more than 17 days. Discontinuation of the drug results in rapid resolution with no sequelae. We report these cases to alert physicians to this uncommon adverse effect of piperacillin-tazobactam and to encourage reporting.
Altered prefrontal correlates of monetary anticipation and outcome in chronic pain
Authors: Martucci Katherine T. , Borg Nicholas , MacNiven Kelly H. , Knutson Brian , Mackey Sean C.
Published: April 2018

Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation—possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.
Sources of opioid medication for misuse in older adults: results from a nationally representative survey
Authors: Schepis Ty S. , McCabe Sean Esteban , Teter Christian J.
Published: April 2018

Despite increasing rates of prescription opioid (PO) misuse in adults 50 years of age and older, little research has investigated such misuse in this population. This work aimed to examine sources of misused opioid medication in adults 50 years and older, with comparisons to younger groups. Data were from the 2009 to 2014 National Survey on Drug Use and Health surveys. Prevalence rates of PO sources, misuse, and PO use disorder (POUD) symptoms were estimated. Design-based logistic regression investigated age-based differences in these factors and the association of sources with POUD symptoms and other concurrent substance use. Nearly half (47.7%) of adults 65 years and older used physician sources for past 30-day PO misuse, with the second highest rates in those 50 to 64 years old (39.2%). Conversely, use of theft (5.3%), purchases (8.5%), or friends/family (for free; 23.2%) to obtain opioids were least common in adults 65 years and older, with prevalence rates of these sources in those 50 years and older closer to those of younger groups. Across those 50 years and older, use of purchases, physician, or multiple sources were associated with elevated POUD symptom prevalence. Older adults, particularly those 65 years and older, use a different pattern of PO sources than adolescents or younger adults, and those using physician sources have elevated POUD symptoms. Physicians are a key avenue for older adults to obtain opioids for misuse, highlighting the potential role of clinicians in limiting such misuse.
Pharmacokinetics of Sustained-Release Oral Dexamphetamine Sulfate in Cocaine and Heroin-Dependent Patients
Authors: Herbrink Maikel , Nuijten Masha , Nuijen Bastiaan , Huitema Alwin D.R. , Beijnen Jos H. , Hendriks Vincent M. , Blanken Peter , Janmohamed Amin , van den Brink Wim
Published: April 2018

Introduction

Research has shown that sustained-release (SR) dexamphetamine is a promising agonist treatment for cocaine dependence. However, little is known about the pharmacokinetics (PKs) of SR oral dexamphetamine. This study examined the PKs of a new SR dexamphetamine formulation in cocaine plus heroin-dependent patients currently in heroin-assisted treatment.

Methods

The study was designed as an open-label PK study in 2 cohorts: n = 5 with once daily 60 mg and n = 7 with once daily 30 mg SR oral dexamphetamine. Five days of blood plasma dexamphetamine concentrations measured with liquid chromatography–mass spectrometry with PK parameter estimates using noncompartmental analysis.

Results

Twelve cocaine-dependent plus heroin-dependent patients in heroin-assisted treatment were included. The initial cohort 1 dose of 60 mg once daily was adjusted to 30 mg after mild to moderate adverse events. After oral administration,tmaxvalues (coefficient of variation %) were 6.0 (17.0%) and 6.3 (16.3%) hours andt1/2were 11 (24.6%) and 12 (25.4%) hours for 60 mg and 30 mg SR dexamphetamine, respectively. At steady state,CSSmaxvalues were reached at 100 (27.5%) ng/mL and 58.4 (14.4%) ng/mL, whereasCSSminvalues were 39.5 (38.9%) ng/mL and 21.8 (19.8%) ng/mL for 60 mg and 30 mg, respectively.

Conclusions

The investigated SR formulation of dexamphetamine showed favorable slow-release characteristics in cocaine and heroin-dependent patients. A dose-proportional steady-state concentration was achieved within 3 days. These findings support the suitability of the SR formulation in the treatment of cocaine dependence.
Decreasing the Time to Administration of First Dose of Antibiotics in Children With Severe Sepsis
Authors: Mittal Yash , Sankar Jhuma , Dhochak Nitin , Gupta Samriti , Lodha Rakesh , Kabra Sushil Kumar
Published: April 2018

Objectives:

To measure difference in median time to antibiotic administration in severe sepsis before and after making process changes and clinical outcomes such as duration of hospitalization and mortality.

Methods:

The study was carried out in the emergency department in children <17 years of age with severe sepsis/septic shock. In phase 1, data were collected and reasons for delayed antibiotic administration were identified. Following this, process changes like creating a triage tool, re-enforcing the severe sepsis protocol and increasing the number of nurses were made to correct the delay. In phase 2, we measured outcomes to compare the effect of the process changes.

Results:

A total of 28 and 13 children each were included during phase 1 and phase 2 of the study respectively. The median interquartile range time to administration of antibiotics from the time of admission decreased significantly from 50 minutes (18, 65) to 20 minutes (15, 20) (p = .02). Duration of hospital stay was longer in phase 1 as compared to phase 2 (12 days vs. 6 days). However, the difference was not statistically significant (p = .1).

Conclusions:

Use of a triage tool, severe sepsis protocol, and increasing the number of nurses resulted in earlier recognition and administration of first dose of antibiotics in children with severe sepsis.
How Useful Is the Flexion–Adduction–Internal Rotation Test for Diagnosing Femoroacetabular Impingement: A Systematic Review
Authors: Shanmugaraj Ajaykumar , Shell Jaymee R. , Horner Nolan S. , Duong Andrew , Simunovic Nicole , Uchida Soshi , Ayeni Olufemi R.
Published: April 2018

Objective:

Clinicians use the flexion, adduction, and internal rotation (FADIR) test in the diagnosis of femoroacetabular impingement (FAI). However, the diagnostic utility of this test remains unclear. The purpose of this review was to determine the utility of the FADIR test in diagnosing FAI.

Data Sources:

MEDLINE, EMBASE, and PubMed were searched using relevant key terms and study screening was performed in duplicate. Patient demographics, diagnostic imaging, and summary measures (eg sensitivity, specificity, etc.) of the FADIR test in patients with FAI were recorded.

Main Results:

Eight studies of levels III (87.5%) and IV (12.5%) evidence were included. Four hundred fifty-two patients (622 hips) with a mean age of 27.0 ± 9.0 were examined. Alpha (75.1%) and/or center-edge (26.8%) angles were used to diagnose hips with FAI. X-ray (78.9%), magnetic resonance imaging (MRI) (16.2%), and computed tomography (CT) (4.8%) were used to confirm the diagnosis of FAI. The sensitivity when confirmed by x-ray, MRI, or CT was 0.08 to 1, 0.33 to 1 and 0.90, respectively. The specificity when confirmed by x-ray and MRI was 0.11 and 1, respectively.

Conclusions:

Although the overall utility of the FADIR test in diagnosing FAI remains unclear given its moderate sensitivity and specificity, it may be a useful screening tool for FAI because of its low risk. Clinicians should consider the variability in sensitivity and specificity values reported and the low quality of literature available. Future studies should use large sample sizes and consistent radiographic measurements to better understand the usefulness of this physical examination maneuver in diagnosing FAI.

Level of Evidence:

Level IV, Systematic Review of Level III and IV studies.
Management of anaphylaxis in Spain: pediatric emergency care providers’ knowledge
Authors: Olabarri Mikel , Gonzalez-Peris Sebastiá , Vázquez Paula , González-Posada Aranzazu , Sanz Nuria , Vinuesa Ana , Diez Nuria , Benito Javier , Mintegi Santiago
Published: April 2018

Background

Acute care providers must diagnose and treat patients with anaphylaxis. The objective was to analyze Spanish pediatric emergency departments’ (ED) providers’ knowledge of the international recommendations for the management of anaphylaxis.

Methods

A web-based survey including providers (both attending and residents) from seven Spanish pediatric EDs was conducted. To analyze the knowledge of the identification of anaphylaxis, we used the diagnostic criteria given by the National Institute of Allergy and Infectious Disease and Food Allergy and the Food Allergy and Anaphylaxis Network (2005). To analyze the management, we used the practical recommendations on the management of anaphylaxis published by the Joint Task Force on Practice Parameters (2014).

Results

A total of 425 physicians received the link and 337 (79.2%) completed the survey (138 attending, 76.6%; 199 residents, 81.2%, P<0.05). More than 90% of the providers correctly identified the anaphylaxis, except for not diagnosing it when reduced blood pressure is detected after exposure to a known allergen (69.7%) and misdiagnosis of anaphylaxis in patients with progressive urticaria with significant angioedema (65.9%). Nearly 100% identified epinephrine as the first-line treatment. Main failures of treatment were related to the position of the patient, the effect of medications in preventing a biphasic reaction, the recommended time to observe patients, and those related to the follow-up. No significant differences were found between attendings and residents.

Conclusion

Even though the Spanish pediatric ED providers’ knowledge of the management of anaphylaxis is good, certain improvement areas are identified in both the identification and the management of these patients.
The Role of the Clinical Nurse Specialist From the Perspective of Parents of Children Born With Cleft Lip and/or Palate in the United Kingdom
Authors: Searle Aidan , Neville Patricia , Ryan Sara , Waylen Andrea
Published: April 2018

Purpose/Aim:

This qualitative study explores parents’ perspectives of the clinical nurse specialist (CNS) after diagnosis of cleft lip and/or palate and while preparing for/after lip or palate closure and other events on the cleft treatment pathway in the United Kingdom.

Design:

Parents with children on the “cleft treatment pathway” were recruited from multiple regions across the United Kingdom. In-depth interviews were conducted with 24 parents of children born with cleft lip and/or palate.

Methods:

Thematic analysis identified 4 key themes: relationship with CNS, information provision, preoperative care and multidisciplinary team (MDT), and postoperative support.

Results:

Clinical nurse specialists are a highly valued point of contact and act as a trusted mediator between parents and other professionals in the MDT. Clinical nurse specialists are important gatekeepers in providing support and information and developing trust after diagnosis and birth and throughout the cleft treatment pathway.

Conclusion:

The present findings affirm the emotional, social, and informational support that the CNS can offer parents whose children are on a cleft treatment pathway. The CNS is a vital member of the cleft service MDT.
Congenital Syphilis Prevention: Strategies, Evidence, and Future Directions
Authors: Plotzker Rosalyn E. , Murphy Ryan D. , Stoltey Juliet E.
Published: April 2018

Background

Congenital syphilis (CS)—the preventable transmission ofTreponema pallidumfrom infected mother to fetus—remains a significant problem worldwide.

Methods

From July through November 2017, 239 articles relevant to CS prevention were identified via keyword searches in PubMed and Google Scholar, ancestry searches, and expert recommendation. Articles were then assessed for (1) measurement of a specified CS or adverse pregnancy outcomes (APOs) and (2) geographic setting in high/upper middle income countries according to United Nations criteria. In total, 119 articles met inclusion criteria. These were then vetted for 1 of 3 arms of CS prevention, after which additional ancestral searches were conducted within each arm to arrive at the final collection of articles per CS prevention strategy—maternal prenatal treatment (n = 33), prenatal screening (n = 24), and public health interventions that support screening and treatment (n = 15).

Results

Of the 7 studies that evaluated treatment with benzathine penicillin G (BPG) use within the context of a modern health care system, all showed BPG to be highly effective in CS prevention; 3 additional studies demonstrated BPG effectiveness in preventing APOs. Ten studies revealed early disease detection through prenatal screening significantly reduces CS and APOs when paired with BPG. There was limited literature evaluating public health interventions, such as partner notification, surveillance, and prenatal screening laws.

Conclusions

Congenital syphilis is a preventable disease, effectively avoided with appropriate prenatal screening and BPG therapy. Increasing syphilis rates among all adults, accompanied by gaps in the provision of prenatal care to women at high risk of infection, are major contributors to CS persistence.
Recent Changes in Prevention Funding to Areas With High Racial and Ethnic Disparities in Sexually Transmitted Disease Rates
Authors: Williams Austin M. , Chesson Harrell W.
Published: April 2018

We examined changes in federal sexually transmitted disease funding allocations to areas with high racial/ethnic disparities in sexually transmitted diseases after the implementation of a funding formula in 2014. The funding formula increased prevention funding allocations to areas with high relative racial/ethnic disparities. Results were mixed for areas with high absolute disparities.
Furosemide Response Predicts Acute Kidney Injury After Cardiac Surgery in Infants and Neonates
Authors: Borasino Santiago , Wall Kevin M. , Crawford Jack H. , Hock Kristal M. , Cleveland David C. , Rahman Fazlur , Martin Kimberly D. , Alten Jeffrey A.
Published: April 2018

Objective:

Cardiac surgery–induced acute kidney injury occurs frequently in neonates and infants and is associated with postoperative morbidity/mortality; early identification of cardiac surgery–induced acute kidney injury may be crucial to mitigate postoperative morbidity. We sought to determine if hourly or 6-hour cumulative urine output after furosemide in the first 24 hours after cardiopulmonary bypass could predict development of cardiac surgery–induced acute kidney injury and other deleterious outcomes.

Design:

Retrospective chart review.

Setting:

Pediatric cardiac ICU.

Patients:

All infants younger than 90 days old admitted to the cardiac ICU from October 2012 to December 2015 who received at least one dose of furosemide in the first 24 hours after cardiopulmonary bypass surgery.

Interventions:

None.

Measurements and Main Results:

Ninety-nine patients met inclusion and exclusion criteria. In total, 45.5% developed cardiac surgery–induced acute kidney injury. Median time between cardiopulmonary bypass and furosemide was 7.7 hours (interquartile range, 4.4–9.5). Six-hour cumulative urine output was 33% lower (p = 0.031) in patients with cardiac surgery–induced acute kidney injury. Area under the curve for prediction of cardiac surgery–induced acute kidney injury was 0.69 (p = 0.002). Other models demonstrated urine output response to furosemide had significant area under the curves for prediction of peak fluid over load greater than 15% (0.68; p = 0.047), prolonged peritoneal dialysis (area under the curve, 0.79; p = 0.007), prolonged mechanical ventilation (area under the curve, 0.79; p < 0.001), prolonged hospitalization (area under the curve, 0.62; p = 0.069) and mortality (area under the curve, 0.72; p = 0.05).

Conclusions:

Urine output response to furosemide within 24 hours of cardiopulmonary bypass predicts cardiac surgery–induced acute kidney injury development and other important morbidity in children younger than 90 days old; prospective validation is warranted.