bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric Properties of the Numerical Rating Scale to Assess Self-Reported Pain Intensity in Children and Adolescents
Authors: Castarlenas Elena , Jensen Mark P. , von Baeyer Carl L. , Miró Jordi 
Published: August 2016

Objectives:
The Numerical Rating Scale-11 (NRS-11) is one of the most widely used scales to assess self-reported pain intensity in children, despite the limited information on its psychometric properties for assessing pain in pediatric populations. Recently, there has been an increase in published findings regarding the strengths and weaknesses of the NRS-11 as a measure of pain in youths. The purpose of this study was to review this research and summarize what is known regarding the reliability and validity of the NRS-11 as a self-report measure of pediatric pain intensity.

Methods:
A literature search was conducted using PubMed, PsycINFO, CINAHL, and the Psychology and Behavioral Sciences Collection from their inception to February 2016.

Results:
A total of 382 articles were retrieved, 301 were screened for evaluation, and 16 were included in the review. The findings of reviewed studies support the reliability and validity of the NRS-11 when used with children and adolescents.

Discussion:
Additional research is needed to clarify some unresolved questions and issues, including (1) the minimum age that children should have to offer valid scores of pain intensity and (2) the development of consensus regarding administration instructions, in particular with respect to the descriptors used for the upper anchor. On the basis of available information, the NRS-11 can be considered to be a well-established measure for use with pediatric populations.
Evaluation of Transversus Abdominis Plane (TAP) Block in Hernia Surgery
Authors: Gao Tao , Zhang Juan-Juan , Xi Feng-Chan , Shi Jia-Liang , Lu Yi , Tan Shan-Jun , Yu Wen-Kui 
Published: August 2016

Background:
Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery.

Methods:
A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications.

Results:
The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] −11.40 mg, −22.41 to −0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P<0.001), the pain scores on rest 24 hours after surgery (WMD: −0.29, −0.55 to −0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: −0.70, −1.33 to −0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group.

Conclusions:
Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.
Sebacoyl Dinalbuphine Ester Extended-release Injection for Long-acting Analgesia
Authors: Yeh Chien-Yuh , Jao Shu-Wen , Chen Jinn-Shiun , Fan Chung-Wei , Chen Hong-Hwa , Hsieh Pao-Shiu , Wu Chang-Chieh , Lee Chia-Cheng , Kuo Yi-Hung , Hsieh Meng-Chiao , Huang Wen-Shih , Chung Yuan-Chiang , Liou Tian-Yuh , Chiu Hsi-Hsiung , Tseng Wen-Ko , Lee Ko-Chao , Wang Jeng-Yi 
Published: August 2016

Objectives:
This study was conducted to evaluate the safety and efficacy of single sebacoyl dinalbuphine ester (SDE) injection (150 mg/2 mL) when administered intramuscularly to patients who underwent hemorrhoidectomy for postoperative long-acting analgesia.

Methods:
A total of 221 patients scheduled for hemorrhoidectomy from 6 centers in Taiwan were randomly divided into SDE group and placebo group, and received the treatment, vehicle or SDE, 1 day before the surgery. Visual analogue scale (VAS) was recorded up to 7 to 10 days. Pain intensity using VAS AUC through 48 hours after surgery was calculated as the primary efficacy endpoint.

Results:
Area under the curve of VAS pain intensity scores (VAS AUC) through 48 hours after hemorrhoidectomy was significantly less in SDE group than those in placebo group (209.93 vs. 253.53). VAS AUC from the end of surgical procedure to day 7 was also significantly different between SDE and placebo group (630.79 vs. 749.94). SDE group consumed significantly less amount of other analgesics, such as PCA ketorolac and oral ketorolac. Median time from the end of surgery to the first use of pain relief medication was also shortened in the placebo group than in the SDE group. Most adverse events were assessed as mild and tolerable in both groups.

Discussion:
SDE injection demonstrated an extended analgesia effect, with a statistically significant reduction in pain intensity through 48 hours and 7 days after hemorrhoidectomy.
Evaluation of Long-Term Cochlear Implant Use in Subjects With Acquired Unilateral Profound Hearing Loss: Focus on Binaural Auditory Outcomes
Authors: Mertens Griet , De Bodt Marc , Van de Heyning Paul 
Published: August 2016

Introduction:
Cochlear implantation (CI) in subjects with unilateral profound sensorineural hearing loss was investigated. The authors of the present study demonstrated the binaural auditory outcomes in a 12- and 36-month prospective cohort outcome study. The present study aimed to do a long-term (LT) evaluation of the auditory outcomes in an analogous study group.

Design:
LT evaluation was derived from 12 single-sided deaf (SSD) CI recipients and from 11 CI recipients with asymmetric hearing loss (AHL). A structured interview was conducted with each subjects. Speech perception in noise and sound localization were assessed in a CIOFF and in a CION condition. Four binaural effects were calculated: summation effect (S0N0), squelch effect (S0NCI), combined head shadow effect (SCIN0), and spatial release from masking (SRM). At the LT evaluation, the contribution of a CI or a bone conduction device on speech perception in noise was investigated in two challenging spatial configurations in the SSD group.

Results:
All (23/23) subjects wore their CI 7 days a week at LT follow-up evaluation, which ranged from 3 to 10 years after implantation. In the SSD group, a significant combined head shadow effect of 3.17 dB and an SRM benefit of 4.33 dB were found. In the AHL group, on the other hand, the summation effect (2.00 dB), the squelch effect (2.67 dB), the combined head shadow effect (3.67 dB), and SRM benefit (2.00 dB) were significant at LT testing. In both the spatial challenging configurations, the speech in noise results was significantly worse in the condition with the bone conduction device compared with the unaided condition. No negative effect was found for the CION condition. A significant benefit in the CION condition was found for sound localization compared with the CIOFF condition in the SSD group and in the AHL group.

Conclusion:
All subjects wore their CI 7 days a week at LT follow-up evaluation. The presence of binaural effects has been demonstrated with speech in noise testing, sound localization, and subjective evaluation. In the AHL group, all investigated binaural effects were found to be significant. In the SSD group on the other hand, only SRM and the head shadow, the two most robust binaural effects, were significantly present. However, it took 12M before the SSD and the AHL subjects significantly benefit from the head shadow effect. These reported results could guide counseling of future CI candidates with SSD and AHL in general.
Age-Dependent Changes in the Pulmonary Renin-Angiotensin System Are Associated With Severity of Lung Injury in a Model of Acute Lung Injury in Rats
Authors: Schouten Laura R. A. , Helmerhorst Hendrik J. F. , Wagenaar Gerry T. M. , Haltenhof Tom , Lutter René , Roelofs Joris J. T. H. , van Woensel Job B. M. , van Kaam Anton H. L. C. , Bos Albert P. , Schultz Marcus J. , Walther Thomas , Wösten-van Asperen Roelie M. 
Published: August 2016

Objectives:
A growing body of evidence suggests that age affects the main pathophysiologic mechanisms of the acute respiratory distress syndrome. This may imply the need for developing age-tailored therapies for acute respiratory distress syndrome. However, underlying molecular mechanisms governing age-related susceptibility first need to be unraveled. In a rat model of acute lung injury, we investigated whether age affects the balance between the two key enzymes of the pulmonary renin-angiotensin system, angiotensin-converting enzyme, and angiotensin-converting enzyme 2. We hypothesized that aging shifts the balance toward the lung injury–promoting angiotensin-converting enzyme, which may form an explanation for the differences in severity of lung injury between different age groups.

Design:
Prospective, randomized controlled animal study.

Setting:
University medical research laboratory.

Subjects:
Infant (15 ± 2 d), juvenile (37 ± 2 d), adult (4 ± 0.2 mo), and elderly (19.5 ± 0.5 mo) male RCCHan Wistar rats.

Interventions:
Lung injury was induced by intratracheal administration of lipopolysaccharide (5 mg/kg) and 4 hours of mechanical ventilation (15 mL/kg).

Measurements and Main Results:
In lipopolysaccharide-exposed and mechanical ventilated rats, angiotensin-converting enzyme activity in bronchoalveolar lavage fluid increased 3.2-fold in elderly when compared with infants. No changes in bronchoalveolar lavage fluid angiotensin-converting enzyme 2 activity were found. In addition, membrane-bound angiotensin-converting enzyme activity decreased. Together with the presence of angiotensin-converting enzyme-sheddase ADAM9 (a disintegrin and metalloproteinase domain–containing protein 9) and an age-dependent increase in tumor necrosis factor-α, an activator of ADAM9, these results indicate increased shedding of angiotensin-converting enzyme in the alveolar compartment, thereby shifting the balance toward the injurious pathway. This imbalance was associated with an increased inflammatory mediator response and more lung injury (wet-to-dry ratio and histology) in elderly rats.

Conclusions:
Increasing age is associated with an imbalance of the pulmonary renin-angiotensin system, which correlates with aggravated inflammation and more lung injury. These changes might form the ground for new therapeutic strategies in terms of dosing and effectiveness of renin-angiotensin system–modulating agents for treatment of acute respiratory distress syndrome.
Survey of U.S. Organ Procurement Organizations Regarding Pediatric Organ Donor Management
Authors: Ream Robert S. , Armbrecht Eric S. 
Published: August 2016

Objective:
To describe the current practice of pediatric organ donor management in the United States for donors declared dead based upon neurologic criteria. The study directs particular attention to how pediatric donors are defined, the use of donor management guidelines, the use of donor management goals, and the involvement of pediatric critical care or transplantation expertise.

Design:
Cross-sectional observational study using a web-based survey and follow-up telephone interview with respondents from U.S. organ procurement organizations. The study also incorporated organ procurement organization–specific data on organ yield for the 4-year period (2010–2013) preceding the study.

Setting:
The 58 U.S. organ procurement organizations.

Subjects:
Respondents chosen by each organ procurement organization.

Interventions:
None.

Measurements and Main Results:
All 58 U.S. organ procurement organizations participated in the study. Fifty-two respondents (90%) indicated that their organ procurement organization distinguished pediatric from adult donors resulting in 28 unique pediatric definitions. Thirty-nine organ procurement organizations utilized some form of written pediatric management guidelines, and 27 (47%) maintained pediatric donor management goals; compliance was infrequently monitored for both guidelines (28%) and goals (33%). A pediatric intensivist was always or usually involved in pediatric donor management at 47 organ procurement organizations (81%); transplant/organ recovery surgeons were always or usually involved at 12 organ procurement organizations (21%). There was an increase in the number of organs transplanted per donor among donors 11–17 years old for organ procurement organizations that used donor management goals for the duration of the period studied (p < 0.01). There was also an increase in the ratio of observed/expected organs transplanted among donors of 0–10 years old for organ procurement organizations that always or usually consulted a transplant/organ recovery surgeon (p = 0.02) although this did not reach our threshold for statistical significance..

Conclusions:
There is little consensus among organ procurement organizations regarding the definition of “pediatric” during organ donor management. Most organ procurement organizations employ written pediatric guidelines and use pediatric intensive care physicians for assistance in managing these donors. There is a positive association between the use of donor management goals and organ yield among pediatric donors in the 11- to 17-year age group.
Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents
Authors: Radbruch Alexander , Weberling Lukas D. , Kieslich Pascal J. , Hepp Johanna , Kickingereder Philipp , Wick Wolfgang , Schlemmer Heinz-Peter , Bendszus Martin 
Published: August 2016

Purpose
Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine.

Materials and Methods
Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods.

Results
The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: −0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: −0.0250 ± 0.0284, P = 0.011).

Conclusions
In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.
The Importance of Reverse Translation for Preclinical Off-Target Mitigation: Quantification and Mitigation of Biases in the FDA Adverse Event Reporting System
Authors: Maciejewski Mateusz , Lounkine Eugen , Whitebread Steven , Farmer Pierre , DuMouchel Bill , Shoichet Brian K. , Urban Laszlo 
Published: August 2016

AbstractThe Food and Drug Administration Adverse Event Reporting System (FAERS) is the primary source for post-marketing pharmacovigilance. Though potentially highly useful, the database reflects reporting biases, stimulated reporting, and suffers from lack of standardization and the use of multiple drug synonyms. These biases can suggest adverse drug reactions (ADRs) where none exist, and can obscure others that do exist. To decrease the noise in FAERS, and to reinforce important associations, we mapped over 750,000 drug identifiers in FAERS to the normalized chemical structures of their ingredients. This illuminated associations that would not otherwise be apparent, and also allowed a time-resolved analysis of ADR reporting. It also revealed similarities between drugs and adverse events across therapeutic classes, enabling unbiased classification of adverse events, indications, and drugs with similar clinical profiles. For instance, comparison of two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib finds distinctive FAERS profiles after time-resolved analysis. We also investigated key idiosyncrasies, such as confusion between drug indications and drug ADRs, which can tar a drug treating a life-threatening disease, like thalidomide’s use against myeloma, with a deadly ADR that is likely the result of the disease itself, multiplications of the same report, which unjustifiably increases its apparent importance, and the correlation of reported ADRs with public events, regulatory announcements, and with publications. Comparing the pharmacological, pharmacokinetic, and clinical ADR profiles of methylphenidate, aripiprazole and risperidone, and of kinase drugs targeting the VEGF receptor (VEGF-R2), demonstrates how underlying molecular mechanisms can emerge from ADR co-analysis. The precautions and methods we describe may enable investigators to avoid confounding chemistry-based associations and reporting biases in FAERS, and illustrate how comparative analysis of ADRs can reveal underlaying mechanisms.
The frequency spectrum of chromatin accessibility in Yorubans points toward a significant role of random genetic drift in shaping the chromatin landscape
Authors: Weavil-Abueg Mariah , Schraiber Joshua G. 
Published: August 2016

AbstractThe function of non-coding variation in the human genome is hotly debated. While much of the genome appears to be involved in some kind of molecular activity, a relatively small portion of the genome appears to be conserved across mammalian species. To try to understand part of this seeming paradox, we examined chromatin accessibility as a model molecular phenotype. We modeled chromatin state as either open or closed as looked at the frequency of open chromatin across 70 Yoruban cell lines. We saw that most regions of chromatin accessibility occurred in only a small number of individuals, although there are a number of regions that are accessible across the entire panel. To delve further into understanding the evolutionary mechanisms, we examined nucleotide diversity in and around accessible regions. We found that in the open chromatin access, low frequency regions had decreased nucleotide diversity, however, they were situated within regions of elevated nucleotide diversity. These results point toward a role of random mutation and genetic drift shaping the distribution of accessible regions in the human genome.
A comparison of Species Distribution Modeling approaches for an under-sampled parasite of public health importance,Echinococcus multilocularis
Authors: Williams Heather M. , Egan Brian , Dittmar Katharina 
Published: August 2016

AbstractBackgroundSpecies distribution models (SDMs) have an important role in predicting the range of emerging and understudied pathogens and parasites. Their use, however, is often limited by the lack of high-resolution unbiased occurrence records.Echinococcus multilocularisis a parasitic cestode of public health importance which is widely distributed throughout Eu rasia and is considered an emerging threat in North America. In common with many parasite species, available data forE. multilocularisoccurrence are spatially biased and often poorly geo-referenced.ResultsHere we produce three separate SDMs using MaxEnt forE. multilocularisusing varying complexities of sampling schemes and environmental predictors, designed to make the best possible use of non-ideal occurrence data. The most realistic model utilized both derived and basic climatic predictors; an occurrence sampling scheme which relied primarily on high resolution occurrences from the literature and a bias grid to compensate for an apparently uneven research effort. All models predicted extensive regions of high suitability forE. multilocularisin North America, where the parasite is poorly studied and not currently under coordinated surveillance.ConclusionsThrough a pragmatic approach to non-ideal occurrence data we were able to produce a statistically well supported SDM for an under-studied species of public health importance. Although the final model was only trained on data from Eurasia, the global model projection encompassed all known occurrences in the United States. The approach defined here may be applicable to many other such species and could provide useful information to direct resources for future field based surveillance programs forE. multilocularisin North America.
Evaluating the genetic diagnostic power of exome sequencing: Identifying missing data
Authors: Lorente-Arencibia Pascual , Guacarán Deyán , Tugores Antonio 
Published: August 2016

ABSTRACTA hurdle of exome sequencing is its limited capacity to represent the entire exome. To ascertain the diagnostic power of this approach we determined the extent of coverage per individual sample. Using alignment data (BAM files) from 15 exome samples, sequences of any length that were below a determined sequencing depth coverage (DP) were detected and annotated with the Ensembl exon database using MIST, a novel software tool. Samples sequenced at 50X mean coverage had, on average, up to 50% of the Ensembl annotated exons with at least one nucleotide (L=1) with a DP<20, improving to 35% at 100X mean coverage. In addition, almost 15% of annotated exons were never sequenced (L=50, DP<1) at 50x mean coverage, reaching down to 5% at 100x. The diagnostic utility of this approach was tested for hypertrophic cardiomyopathy, a genetically heterogeneous disease, where exome sequencing covered as much as 80% of all candidate genes exons at DP≥20. This report stresses the value of identifying, precisely, which sequences are below a specific depth in an individual’s exome, and provides a useful tool to assess the potential and pitfalls of exome sequencing in a diagnostic or gene discovery setting.COMPETING INTERESTSThe authors declare no conflicts of interest.