bluuebunny/crossref_metadata_2025 huggingface dataset:
tableone: An open source Python package for producing summary statistics for research papers
Authors: Pollard Tom J , Johnson Alistair E W , Raffa Jesse D , Mark Roger G
Published: May 2018

Objectives

In quantitative research, understanding basic parameters of the study population is key for interpretation of the results. As a result, it is typical for the first table (“Table 1”) of a research paper to include summary statistics for the study data. Our objectives are 2-fold. First, we seek to provide a simple, reproducible method for providing summary statistics for research papers in the Python programming language. Second, we seek to use the package to improve the quality of summary statistics reported in research papers.

Materials and Methods

The tableone package is developed following good practice guidelines for scientific computing and all code is made available under a permissive MIT License. A testing framework runs on a continuous integration server, helping to maintain code stability. Issues are tracked openly and public contributions are encouraged.

Results

The tableone software package automatically compiles summary statistics into publishable formats such as CSV, HTML, and LaTeX. An executable Jupyter Notebook demonstrates application of the package to a subset of data from the MIMIC-III database. Tests such as Tukey’s rule for outlier detection and Hartigan’s Dip Test for modality are computed to highlight potential issues in summarizing the data.

Discussion and Conclusion

We present open source software for researchers to facilitate carrying out reproducible studies in Python, an increasingly popular language in scientific research. The toolkit is intended to mature over time with community feedback and input. Development of a common tool for summarizing data may help to promote good practice when used as a supplement to existing guidelines and recommendations. We encourage use of tableone alongside other methods of descriptive statistics and, in particular, visualization to ensure appropriate data handling. We also suggest seeking guidance from a statistician when using tableone for a research study, especially prior to submitting the study for publication.
On the existence of a luminosity threshold of GRB jets in massive stars
Authors: Aloy M A , Cuesta-Martínez C , Obergaulinger M
Published: May 2018

Motivated by the many associations of gamma-ray bursts (GRBs) with energetic supernova (SN) explosions, we study the propagation of relativistic jets within the progenitor star in which an SN shock wave may be launched briefly before the jets start to propagate. Based on analytic considerations and verified with an extensive set of 2D axisymmetric relativistic hydrodynamic simulations, we have estimated a threshold intrinsic jet luminosity, $L_{\rm j}^{\rm thr}$, for successfully launching a jet. This threshold depends on the structure of the progenitor and, thus, it is sensitive to its mass and to its metallicity. For a prototype host of cosmological long GRBs, a low-metallicity star of 35 M⊙, it is $L_{\rm j}^{\rm thr}\simeq 1.35\times 10^{49}$ erg s−1. The observed equivalent isotropic gamma-ray luminosity, $L_{\rm \gamma ,iso,BO} \simeq 4 \epsilon _\gamma L_{\rm j} \theta _{\rm BO}^{-2}$, crucially depends on the jet opening angle after breakout, θBO, and on the efficiency for converting the intrinsic jet luminosity into γ-radiation, εγ. Highly energetic jets can produce low-luminosity events if either their opening angle after the breakout is large, which is found in our models, or if the conversion efficiency of kinetic and internal energy into radiation is low enough. Beyond this theoretical analysis, we show how the presence of an SN shock wave may reduce this luminosity threshold by means of numerical simulations. We foresee that the high-energy transients released by jets produced near the luminosity threshold will be more similar to llGRBs or X-ray flashes than to GRBs.
The Cumulative Impact of Harm Reduction on the Swiss HIV Epidemic: Cohort Study, Mathematical Model, and Phylogenetic Analysis
Authors: Marzel Alex , Kusejko Katharina , Weber Rainer , Bruggmann Philip , Rauch Andri , Roth Jan A , Bernasconi Enos , Calmy Alexandra , Cavassini Matthias , Hoffmann Matthias , Böni Jürg , Yerly Sabine , Klimkait Thomas , Perreau Matthieu , Günthard Huldrych F , Kouyos Roger D ,   Swiss HIV Cohort Study, Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: May 2018

Background

Human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs) is increasing in the United States due to the recent opioid epidemic and is the leading mode of transmission in Eastern Europe.

Methods

To evaluate the overall impact of HIV harm reduction, we combined (1) data from the Swiss HIV Cohort Study and public sources with (2) a mathematical model expressed as a system of ordinary differential equations. The model reconstructs the national epidemic from the first case in 1980 until 2015. Phylogenetic cluster analysis of HIV-1 pol sequences was used to quantify the epidemic spillover from IDUs to the general population.

Results

Overall, harm reduction prevented 15903 (range, 15359–16448) HIV infections among IDUs until the end of 2015, 5446 acquired immune deficiency syndrome (AIDS) deaths (range, 5142–5752), and a peak HIV prevalence of 50.7%. Introduction of harm reduction 2 years earlier could have halved the epidemic, preventing 3161 (range, 822–5499) HIV infections and 1468 (range, 609–2326) AIDS deaths. Suddenly discontinuing all harm reduction in 2005 would have resulted in outbreak re-emergence with 1351 (range, 779–1925) additional HIV cases. Without harm reduction, the estimated additional number of heterosexuals infected by HIV-positive IDUs is estimated to have been 2540 (range, 2453–2627), which is equivalent to the total national reported incidence among heterosexuals in the period of 2007 to 2015.

Conclusions

Our results suggest that a paramount, population-level impact occurred because of the harm reduction package, beyond factors that can be explained by a reduction in risk behavior and a decrease in the number of drug users over time.
Towards a Definition for Health Care–Associated Infection
Authors: Friedman N Deborah , Levit Dana , Taleb Eyal , Marcus Gil , Michaeli Leah , Broide Mor , Mengesha Bethlehem , Zaidenstein Ronit , Lazarovitch Tsilia , Dadon Mor , Kaye Keith S , Marchaim Dror
Published: May 2018

Background

Health care–associated infection (HcAI) is a term frequently used to describe community-onset infections likely to be caused by multidrug-resistant organisms (MDROs). The most frequently used definition was developed at Duke University Medical Center in 2002 (Duke-2002). Although some professional societies have based management recommendations on Duke-2002 (or modifications thereof), neither Duke-2002 nor other variations have had their performance measured.

Methods

A case–control study was conducted at Assaf Harofeh Medical Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable model was used to develop a prediction score for HcAI, measured by the presence of MDRO infection on admission. The performances of this new score and previously developed definitions at predicting MDRO infection on admission were measured.

Results

Of the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled patients with nosocomial infections (n = 189) in terms of epidemiological characteristics, illness acuity, and outcomes more than patients with non-MDRO-BSI on admission (n = 215). The performances of both the newly developed score and the Duke-2002 definition to predict MDRO infection on admission were suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68, respectively).

Conclusions

Although the term HcAI is frequently used, its definition does not perform well at predicting MDRO infection present on admission to the hospital. A validated score that calculates the risk of MDRO infection on admission is still needed to guide daily practice and improve patient outcomes.
Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique
Authors: McGovern Robert A , Alomar Soha , Bingaman William E , Gonzalez-Martinez Jorge
Published: May 2018

BACKGROUND

The management of medically refractory epilepsy patients who are not surgical candidates has remained challenging. Closed loop—or responsive—neurostimulation (RNS) is now an established therapy for the treatment of epilepsy with specific indications. The RNS® system (NeuroPace Inc, Mountainview, California) has recently been shown to be effective in reducing the seizure frequency of partial onset seizures. The electrode design consists of either intracerebral depth electrodes or subdural strip electrodes, and stereotaxis is typically used to guide placement into the EZ. Details on the operative techniques used to place these electrodes have been lacking.

OBJECTIVE

To address the advantage of using a robotic-assisted technique to place depth electrodes for RNS® system placement compared to the typical frame-based or frameless stereotactic systems.

METHODS

We retrospectively reviewed our single center, technical operative experience with RNS® system placement using robotic assistance from 2014 to 2016 via chart review.

RESULTS

Twelve patients underwent RNS® system placement using robotic assistance. Mean operative time was 121 min for a median of 2 depth electrodes with mean deviation from intended target of ∼3 mm in x, y, and z planes. Two patients developed wound infections, 1 of whom was reimplanted. Seizures were reduced by ∼40% at 2 yr, similar to the results seen in the open label portion of the pivotal RNS trial.

CONCLUSION

Robotic-assisted stereotaxis can be used to provide a stable and accurate stereotactic platform for insertion of intracerebral RNS electrodes, representing a safe, efficient and accurate procedure.
Spatially resolved spectroscopy of non-thermal X-rays in RX J1713.7−3946 with Chandra
Authors: Okuno Tomoyuki , Tanaka Takaaki , Uchida Hiroyuki , Matsumura Hideaki , Tsuru Takeshi Go
Published: May 2018

The young shell-type supernova remnant (SNR) RX J1713.7−3946 has been studied as a suitable target to test the SNR paradigm for the origin of Galactic cosmic rays. We present a spatially resolved spectroscopy of the non-thermal X-ray emission in RX J1713.7−3946 with Chandra. In order to obtain X-ray properties of the filamentary structures and their surrounding regions, we divide the southeastern (SE), southwestern (SW), and northwestern (NW) parts of the SNR into subregions on the typical order of several 10" and extract spectra from each subregion. Their photon indices are significantly different among the subregions, with a range of 1.8 < Γ < 3. In the SE part, the clear filaments are harder (Γ ∼ 2.0) than the surrounding regions. This is a common feature often observed in young SNRs and naturally interpreted as a consequence of synchrotron cooling. On the other hand, the bright filamentary regions do not necessarily coincide with the hardest regions in the SW and NW parts. We also find the SW filamentary region is relatively rather soft (Γ ∼ 2.7). In addition, we find that hard regions with photon indices of 2.0–2.2 exist around the bright emission although the hard regions lie in the downstream region and the bright emission does not appear to be the blast wave shock front. Both the aforementioned characteristic regions in SW are located close to peaks of the interstellar gas. We discuss possible origins of the spatial variation of the photon indices, paying particular attention to the shock–cloud interactions.
Changes in Teaching Hospitals’ Community Benefit Spending After Implementation of the Affordable Care Act
Authors: Alberti Philip M. , Sutton Karey M. , Baker Matthew
Published: May 2018

Purpose

U.S. teaching hospitals that qualify as 501(c)(3) organizations (a not-for-profit designation) are required to demonstrate community benefit annually. Increases in health insurance access driven by Affordable Care Act (ACA) implementation, along with new regulations, research opportunities, and educational expectations, may be changing hospitals’ allocations of community benefit dollars. This study aimed to describe changes in teaching hospitals’ community benefit spending between 2012 (pre-ACA implementation) and 2015 (post-ACA implementation), and to explore differences in spending changes between hospitals in Medicaid expansion and nonexpansion states.

Method

In 2017, for each teaching hospital member of the Association of American Medical Colleges’ (AAMC’s) Council of Teaching Hospitals and Health Systems required to submit Form 990s to the Internal Revenue Service, the authors sought community benefit spending data for 2012 and 2015 as reported on Schedule H.

Results

The analysis included 169 pairs of Form 990s representing 184 AAMC member teaching hospitals (93% of 198 eligible hospitals). Compared with 2012, hospitals in 2015 spent $3.1 billion (20.14%) more on community benefit despite spending $804 million (16.17%) less on charity care. Hospitals in Medicaid expansion states increased spending on subsidized health services and Medicaid shortfalls at rates higher than hospitals in nonexpansion states. The latter increased spending at higher rates on community health improvement and cash/in-kind contributions.

Conclusions

After ACA implementation, teaching hospitals increased their overall community benefit spending while their charity care spending declined. Changes in community benefit spending differed according to states’ Medicaid expansion status, demonstrating hospitals’ responsiveness to state and local realities.
Neuromodulation in Pediatrics
Authors: Kim Eugene , Gamble Sean , Schwartz Adina , Cucchiaro Giovanni
Published: May 2018

Objectives:

Neuromodulation, particularly intrathecal drug delivery systems and spinal cord stimulators (SCSs), can be a valuable tool when treating chronic pain in adults. However, there is a paucity of literature with regard to its use in pediatrics.

Materials and Methods:

We present a series of 14 children and adolescents with intractable pain who received a SCS or a pump for the intrathecal delivery of medications between 2010 and 2016 at our institution.

Results:

During the study period, we placed 10 intrathecal pumps and 4 SCSs with an average age of 17 years old. Pain scores significantly improved after the implant (P<0.007) and function improved in 79% of patients. Opioid use was also significantly reduced. Three patients eventually had their device removed due to psychiatric comorbidities. Four patients had complications that were treated without further sequelae.

Conclusions:

Neuromodulation can offer important options in treating some pediatric chronic pain patients. In-depth knowledge of primary disease and strict patient selection in the context of the patient’s social situation is vital to successful treatment.
Radiological Evaluation of Craniocervical Region in Patients with Basilar Invagination
Authors: Ji Wei , Xu Xiaolin , Wu Zenghui , Liu Xiang , Kong Ganggang , Huang Zucheng , Chen Jianting
Published: May 2018

Study Design.

A retrospective analysis of collected data.

Objective.

Our study aims to present the morphology of cranial-cervical spinal canal in basilar invagination (BI) patients.

Summary of Background Data.

BI is characterized by protrusion of the odontoid process into the foramen magnum (C0), leading to compression of the cervicomedullary junction. However, no study has ever clarified the anatomical diameters of spinal canal in patients with BI.

Methods.

The study retrospectively examined computed tomography (CT)-based anatomical characteristics in a cohort of 84 patients with and without BI. We measured the anteroposterior diameter (APD) and transversal diameter (TVD) of spinal canal from C0 to C4, together with the area of vertebral canal (Area). Independent samples t test was used for statistical analysis.

Results.

The APD in the BI group was shorter than the control group from C0 to C2 (C0: 27.98 vs. 35.11 mm, P < 0.001; C1: 11.87 vs. 16.91 mm, P < 0.001; C2: 12.91 vs. 14.84 mm, P < 0.001), but it became longer from C3 to C4. The TVD of the BI group was significantly wider from C0 to C3 (C0: 30.59 vs. 28.54 mm, P < 0.001; C1: 31.31 vs. 25.98 mm, P < 0.001; C2: 21.56 vs. 20.40 mm, P = 0.01; C3: 22.45 vs. 21.23 mm, P = 0.013), and it had no significance at C4. The Area showed no difference between the two groups from C1 to C2, but it turned larger at C3 and C4 in BI patients.

Conclusion.

BI patients may have shorter APD from C0 to C2, which could be the leading cause of neurological compression, necessitating decompression on sagittal plane. Below the pathological levels, BI patients have larger spinal canal than general population.

Level of Evidence: 3
Evidence-based Care Bundles for Preventing Surgical Site Infections in Spinal Instrumentation Surgery
Authors: Yamada Koji , Abe Hiroaki , Higashikawa Akiro , Tonosu Juichi , Kuniya Takashi , Nakajima Koji , Fujii Haruko , Niwa Kazuki , Shinozaki Tomohiro , Watanabe Kenichi , Sakae Tanaka , Okazaki Hiroshi
Published: May 2018

Study Design.

A retrospective study, using prospectively collected data.

Objective.

The aim of this study was to evaluate the impact of evidence-based care bundles for preventing surgical site infections (SSIs) in spinal instrumentation surgery.

Summary of Background Data.

About half of all SSIs are preventable via evidence-based methods. For successful SSI prevention, the bacterial load must be minimized, and methicillin-resistant Staphylococcus aureus (MRSA) protection must be maximized. However, it is difficult to cover all of these requirements by single preventative method.

Methods.

We screened consecutive patients scheduled for spinal instrumentation surgeries at a single tertiary referral hospital for high surgical, SSI, and MRSA colonization risks. Evidence-based care bundles were implemented for high-risk patients and included 1) additional vancomycin prophylaxis, 2) diluted povidone-iodine irrigation, and 3) nasal and body decontamination. Patient demographics, comorbidities, operative features, and SSIs reported to the Japanese Nosocomial Infections Surveillance system were prospectively obtained in the same method by the same assessor and were used for the analyses. The results were compared before and after the application of the bundle.

Results.

There were 1042 spinal instrumentation surgeries (741 before and 301 after care bundles) performed from November 2010 to December 2015. Of 301 surgeries, 57 cases (18.9%) received care bundles. There were no significant differences in patient backgrounds before and after the intervention. The SSI rate decreased significantly from 3.8% to 0.7% (P < 0.01) after the intervention, with an overall 82% relative risk reduction. A significant protective effect was observed in the multivariate analysis (adjusted odds ratio 0.18, 95% confidence interval: 0.04–0.77, P = 0.02). There were no MRSA-related SSIs among those that received care bundles, even though MRSA was the predominant pathogen in the study population.

Conclusion.

Evidence-based care bundles, applied in selected high-risk spinal instrumentation cases, minimized bacterial load, maximized MRSA protection, and significantly reduced SSI rates without topical vancomycin powder.

Level of Evidence: 4
Adjacent Segment Disease After Single Segment Posterior Lumbar Interbody Fusion for Degenerative Spondylolisthesis
Authors: Okuda Shinya , Nagamoto Yukitaka , Matsumoto Tomiya , Sugiura Tsuyoshi , Takahashi Yoshifumi , Iwasaki Motoki
Published: May 2018

Study Design.

A retrospective study.

Objective.

The aim of this study was to investigate the incidence of adjacent segment disease (ASD) at 2, 5, and 10 years after primary posterior lumbar interbody fusion (PLIF), and clinical features of ASD.

Summary of Background Data.

Few reports have examined ASD after PLIF with more than 10 years of follow-up. Furthermore, no reports have examined limited conditions of preoperative pathology, fusion segment, and fusion method with long follow-up.

Methods.

Data were reviewed for 128 patients who underwent single-segment PLIF for L4 degenerative spondylolisthesis and could be followed for at least 10 years. Mean age at the time of surgery was 63 years, and mean follow-up was 12.4 years. Follow-up rate was 62.4%. ASD was defined as radiological ASD (R-ASD), radiological degeneration adjacent to the fusion segment by plain X-rays and magnetic resonance imaging (MRI); symptomatic ASD (S-ASD), a symptomatic condition due to neurological deterioration at the adjacent segment degeneration; and operative ASD (O-ASD), S-ASD requiring revision surgery.

Results.

Incidences of each ASD at 2, 5, and 10 years after primary PLIF were 19%, 49%, and 75% for R-ASD, 6%, 14%, and 31% for S-ASD, and 5%, 9%, and 15% for O-ASD, respectively. O-ASD incidence was 24% at final follow-up. O-ASD peak was bimodal, at 2 and 10 years after primary PLIF. O-ASD was mainly observed at the cranial segment (77%), followed by the caudal segment (13%) and both cranial and caudal segments (10%). With respect to O-ASD pathology, degenerative spondylolisthesis was observed in 52%, spinal stenosis in 39%, and disc herniation in 10%.

Conclusion.

Incidences of R-ASD, S-ASD, and O-ASD at 10 years after primary PLIF were 75%, 31%, and 15%, respectively. With respect to O-ASD pathology, degenerative spondylolisthesis at the cranial segment was the most frequent.

Level of Evidence: 4
Distinct Clinical and Genetic Findings in Iranian Patients With Glycogen Storage Disease Type 3
Authors: Nazari Ferdos , Sinaei Farnaz , Nilipour Yalda , Petit François , Oveisgharan Shahram , Nassiri-Toosi Mohsen , Razzaghy-Azar Maryam , Mahmoudi Mahdi , Nafissi Shahriar
Published: May 2018

Objectives:

Glycogen storage disease type 3 (GSD-III) is a rare inherited metabolic disorder caused by glycogen debranching enzyme deficiency. Various pathogenic mutations of the AGL gene lead to abnormal accumulation of glycogen in liver, skeletal, and cardiac muscles. Here, we report distinct clinical and genetic data of Iranian patients with GSD-III.

Methods:

Clinical and laboratory data of 5 patients with GSD-III were recorded. Genetic investigation was performed to identify the causative mutations.

Results:

Three patients had typical liver involvement in childhood and one was diagnosed 2 years after liver transplantation for cirrhosis of unknown etiology. Four patients had vacuolar myopathy with glycogen excess in muscle biopsy. All patients had novel homozygous mutations of the AGL gene namely c.378T>A, c.3295T>C, c.3777G>A, c.2002-2A>G, and c.1183C>T.

Conclusions:

This is the first comprehensive report of patients with GSD-III in Iran with 2 uncommon clinical presentations and 5 novel mutations in the AGL gene.
Barriers to Preceptor Placement for Nurse Practitioner Students
Authors: Hawkins Martha D.
Published: May 2018

Advanced practice registered nurses (APRNs) are positioned to fill healthcare gaps in the looming primary care provider shortage, if clinical educational needs can be met. Issues with preceptor placements for APRNs have been hotly debated in nursing education but not well studied. This article presents a case study of a quality improvement project, describing the experiences of a Clinical Preceptor Placement Coordinator for APRN students for a small Midwestern university. Barriers identified in finding preceptor placements for students are delineated, and suggestions for solutions and further research are given to address this growing problem.
Pneumocystis Infection in Children
Authors: Inagaki Kengo , Blackshear Chad , Hobbs Charlotte V.
Published: May 2018

Background:

Although the epidemiology of immunocompromising condition in children has evolved over time, updated epidemiology of pediatric pneumocystis infection in the United States is not available.

Methods:

We performed a retrospective analysis using the Kids’ Inpatient Database, a nationally representative sample of US pediatric hospital discharges collected in 1997, 2000, 2003, 2006, 2009 and 2012. Pneumocystis cases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification, code 136.3 among children 0–18 years of age. Demographic data of cases with and without mortality were compared.

Results:

We identified 1902 [standard error (SE): 95] pneumocystis cases during the study period. The pneumocystis hospitalization rate decreased from 7.5 (SE: 0.91) to 2.7 (SE: 0.31) per a million US children from 1997 to 2012 (63.2% decrease). Cases with HIV infection decreased from 285 (SE: 56) cases in 1997 to 29 (SE: 7) cases in 2012, whereas hematologic malignancy and primary immunodeficiency became more prominent. Infants were the most commonly affected [510 cases (SE: 40)]. All-cause in-hospital mortality was 11.7% (SE: 1.3%) and was particularly high among cases with hematopoietic stem cell transplant [32.4%(SE: 7.1%); P < 0.001].

Conclusions:

Pneumocystis infection in children showed a marked decrease from 1997 to 2012 in the United States, largely driven by the reduction in HIV-associated cases, and cases with non-HIV illnesses became more prominent. Hematopoietic stem cell transplant–associated cases had particularly high mortality. Clinicians should be aware of high-risk groups that may benefit from chemoprophylaxis, particularly in infancy.
Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice
Authors: Millecamps Magali , Stone Laura S.
Published: May 2018

Low back pain (LBP) is associated with both axial discomfort and radiating leg pain. Although intervertebral discs are suspected as the source of pain in some individuals, the relationship between disc degeneration and back pain remains controversial. The goals of this study were to investigate the long-term impact of L4/L5 disc puncture on disc degeneration and the subsequent emergence, persistence, and underlying mechanisms of axial and radiating LBP in mice. L4 to L5 discs were punctured on the ventral aspect with a 30 gauge needle in 3-month old female CD1 mice, and the development of behavioral signs of axial discomfort (tail suspension and grip force), radiating hypersensitivity (von Frey and acetone), and motor impairment (rotarod) were monitored. Disc degeneration was assessed using X-ray, T2–magnetic resonance imaging, and histology, and persisted for up to 1 year. Innervation was quantified by immunohistochemistry using the pan-neuronal marker PGP9.5. Behavioural signs of axial discomfort peaked 3 to 9 months after injury. During the peak, local nerve density was increased. A transient increase in hypersensitivity to cold, suggestive of radiating pain, was observed 2 weeks after injury. Radiating pain then reemerged 9 to 12 months after injury in half the animals and correlated with increased dorsal innervation and reduced disc height at these late time points. In summary, a single-level disc injury is sufficient to induce prolonged disc degeneration and delayed axial and radiating pain. This model will be useful to investigate underlying mechanisms and potential therapeutic strategies for discogenic LBP.
Racial differences in opioid prescribing for children in the United States
Authors: Groenewald Cornelius B. , Rabbitts Jennifer A. , Hansen Elizabeth E. , Palermo Tonya M.
Published: May 2018

Racial differences exist in analgesic prescribing for children during emergency department and ambulatory surgery visits in the United States; however, it is unknown whether this is true in the outpatient setting. We examined racial and ethnic differences in outpatient analgesic prescribing using nationally representative data from 113,929 children from the Medical Expenditure Panel Survey. We also examined whether patient–provider race and ethnic concordance was associated with opioid prescription. White children were more commonly prescribed opioids as compared to minorities (3.0% vs 0.9%-1.7%), except for Native American children who had similar rates of opioid prescription (2.6%) as white children. Minorities were more likely to receive nonopioid analgesics than white children (2.0%-5.7% vs 1.3%). Although most white children had race-concordant providers (93.5%), only 34.3% of black children and 42.7% of Hispanic children had race-concordant providers. Among black children, having a race concordant usual source of care provider was associated with a decreased likelihood of receiving an opioid prescription as compared to having a white usual source of care provider (adjusted odds ratio [95% confidence interval] = 0.51 [0.30-0.87]). For all other racial groups, patient–provider race-concordance was not associated with likelihood of opioid prescription. Racial differences exist in analgesic prescriptions to children at outpatient health care visits in the United States, with white children more likely to receive opioids and minorities more likely to receive nonopioid analgesics. Health care providers' race and ethnicity may play a significant role in extant analgesic differences. Further work should focus on understanding the role of provider race and ethnicity in analgesic differences to children in the United States.
The Human Cochlear Aqueduct and Accessory Canals: a Micro-CT Analysis Using a 3D Reconstruction Paradigm
Authors: Atturo Francesca , Schart-Morén Nadine , Larsson Sune , Rask-Andersen Helge , Li Hao
Published: May 2018

Objective:

We sought to study the anatomic variations of the cochlear aqueduct and its accessory canals in human temporal bones using micro-CT and a 3D reconstruction paradigm. More knowledge about the anatomic variations of these structures, particularly at the basal turn of the cochlea and round window niche, may be important to better preserve residual hearing as well as the neural supply during cochlear implant surgery.

Methods:

An archival collection of 30 human temporal bones underwent micro-CT and 3D reconstruction. A surface enhancement paradigm was applied. The application displays reconstructed slices as a 3D object with realistic 3D visualization of scanned objects. Virtual sectioning or “cropping” of the petrous bone presented subsequent areas. Thereby, the bony canals could be followed from inside the basal turn of cochlea and middle ear to the jugular foramen.

Results:

The cochlear aqueduct was always paralleled by an accessory canal containing the inferior cochlear vein. It ran from the basal turn of the cochlea and exited laterally in the jugular foramen. In 70% of the cases, a secondary accessory canal was observed and it derived mostly from a depression or infundibulum located in the floor of the round window niche. This canal also exited in the jugular foramen. The secondary accessory canal occasionally anastomosed with the primary accessory canal suggesting that it contains a vein that drains middle ear blood to the cranial sinus.

Conclusion:

Micro-CT with 3D surface reconstruction paradigm offers new possibilities to study the topographic anatomy of minor details in the human inner ear. The technique creates simulated transparent “castings” of the labyrinth with a coinciding surface view through enhancement of contrast between boundaries. Accessory canals that drain blood from the cochlea, spiral ganglion, and middle ear could be characterized three-dimensionally.
Refractory Constipation
Authors: Staller Kyle
Published: May 2018

Most clinicians will agree that chronic constipation is characterized by abnormal bowel movement consistency and/or frequency plus or minus evacuation symptoms, but patient perception of constipation varies widely and includes symptoms that may or may not meet official defining criteria. Although intermittent constipation is extremely common, only a small minority of patients seek care for their symptoms. Among these patients, dissatisfaction with the currently available laxative options is not uncommon, and many patients will require specialized care for severe or refractory symptoms—especially those with abdominal pain, irritable bowel syndrome overlap, bloating or distention, and psychological comorbidities. This review outlines a physiological assessment of the patient with refractory constipation, exploring treatment options among patients with slow transit, rectal evacuation disorders, and normal transit. In addition, we explore nonlaxative approaches to normal-transit patients bothered by ongoing symptoms, with an emphasis on the biopsychosocial model of functional gastrointestinal disease and treatment of visceral hypersensitivity using neuromodulators. Finally, we propose a comprehensive evaluation algorithm for the management of patients with refractory slow-transit constipation considering surgery and examine surgical options including colectomy and cecostomy using an antegrade continent enema.
Constipation in critical care patients: both timing and duration matter
Authors: Prat Dominique , Messika Jonathan , Millereux Maude , Gouezel Corentin , Hamzaoui Olfa , Demars Nadège , Jacobs Frédéric , Trouiller Pierre , Ricard Jean-Damien , Sztrymf Benjamin
Published: May 2018

Objective

Most of the studies have defined constipation as a period without stool after ICU admission. We aimed to test the impact of both duration and timing of infrequent defecation in critical care patients.

Patients and methods

We performed a prospective, bi-center, observational study. Patients were divided into three subgroups: ‘not constipated’, ‘3–5 days’, and ‘at least 6 days’ (longest period without stool passage, respectively, shorter than 3 days, 3–5 days, and ≥6 days). Furthermore, ‘early’ constipated patients were defined as those for whom the longest time to stool passage occurred just after ICU admission, whereas for ‘late’ constipated patients the longest period without stool occurred later during ICU stay.

Results

A total of 182 patients were included: the mean age was 67.2 years (54.4–78.9 years), 80 were women, and simplified acute physiology score II was 42 (34–52). In all, 42 (23.1%), 82 (45.1%), and 58 (31.8%) belonged to the nonconstipated, 3–5 days, or greater than or equal to 6 days subgroup of patients, respectively. Time spent under mechanical ventilation and ICU length of stay was longer in the greater than or equal to 6 days subgroups as compared with both other subgroups. ICU stay was longer in the 3–5 days subgroup as compared with the not constipated patients. Furthermore, the late patients of the greater than or equal to 6 days subgroups exhibited worse survival as compared with all other patients.

Conclusion

Both timing and duration of infrequent defecation seem to have an impact on critical care patient’s outcome, and should therefore be included in the diagnostic criteria.
Evaluation of the Use of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients
Authors: Timaeus Sarah , Elder Joshua , Franco Kyle
Published: May 2018

A neurokinin-1 (NK1) receptor antagonist is recommended with a 5-HT3 receptor antagonist and dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving highly emetogenic chemotherapy. Data for fosaprepitant use in pediatric patients is lacking. A retrospective chart review was conducted using an electronic medical record to characterize the use of fosaprepitant in patients aged 10 months to 18 years at a single institution from August 2015 to January 2017. Thirty-nine patients received fosaprepitant 4 mg/kg (maximum, 150 mg) for prevention of CINV, and 35 were included in the analysis. Ten patients 5 years of age or older who received fosaprepitant after October 2016 were eligible for a follow-up phone call to assess control of delayed CINV. Complete control of emesis was observed in 89% of patients during the acute phase, 63% during the delayed phase, and 60% overall. Overall incidence of nausea as documented in the medical record was 43%. Among the 10 patients who completed follow-up phone calls, 30% experienced emesis and 50% experienced nausea after discharge. Fosaprepitant may be safe and effective in the prevention of CINV in pediatric patients as young as 10 months of age.
Pediatric Gastrointestinal Posttransplant Lymphoproliferative Disorder: Incidence, Clinical Characteristics, and Impact of Major Surgical Interventions Upon Overall Survival
Authors: Dziegielewski Claudia , Contreras Rodrigo , Weitzman Sheila , Gerstle Justin T.
Published: May 2018

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation. A common site for PTLD development is the gastrointestinal (GI) tract. The purpose of this study was to evaluate the incidence, clinical features, and overall survival of pediatric patients with GI-PTLD, and to assess whether major surgical interventions increased mortality. Records of pediatric transplant patients who developed GI-PTLD between January 2000 and June 2015 were retrospectively reviewed at our institution. Of 814 patients who received solid organ transplants, 34 (4%) developed GI-PTLD. Lung and multiorgan transplants had the highest incidence of GI-PTLD (both 11%). Patients often had multisite GI involvement (47%). Within the first year of transplantation, 38% of the 34 patients developed GI-PTLD. Of the patients with Epstein-Barr Virus–positive disease, 12/22 (55%) presented in the first 12 months of transplantation, compared with only 1/12 (8%) of the patients with Epstein-Barr Virus–negative disease (P=0.002). Major surgical interventions were required in 41% of patients; overall survival rate for these surgical patients was 71%, compared with 60% for patients not requiring major surgical interventions (P=0.49). Despite multimodal treatments, overall survival remains poor for patients with GI-PTLD; however, major surgical intervention did not significantly impact overall survival in this cohort.
Fast Ablation of Anogenital Warts of the Urinary Meatus by Low-dose Ingenol Mebutate Gel
Authors: Braun Stephan A. , Barsch Martin , Gerber Peter A.
Published: May 2018

Therapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate gel.
Functional Outcome of Elderly Hip Fracture Patients Is Not Affected By Prefracture Dementia
Authors: Mizrahi Eliyahu Hayim , Lubart Emilia , Adunsky Abraham
Published: May 2018

Objective

The aim of the study was to examine whether a diagnosis of prefracture dementia (PFD) affects functional outcome at discharge from a geriatric rehabilitation setting.

Design

A total of 211 consecutive elderly hip fracture patients were evaluated retrospectively. We used the Functional Independence Measure (FIM) and analyzed data by t test, χ2 test, and multiple linear regression analysis.

Results

Patients with PFD were older (P = 0.001), presented with lower Mini-Mental State Examination scores (P < 0.001) and lower prefracture function (P < 0.001). Total-FIM and motor-FIM scores at admission and discharge, as well as FIM gain scores at discharge, were lower among patients with PFD, compared with nonprefracture dementia (NPFD) patients (P < 0.001). The FIM daily gains (efficiency) (P < 0.001) and Montebello relative functional scores (P < 0.001) were also lower in PFD, compared with patients with NPFD. However, linear regression analysis showed that PFD did not predict total, motor, or FIM gain at discharge (β = −0.11, P = 0.115; β = −0.06, P = 0.412; β = −0.099, P = 0.329, respectively). Upon discharge, patients with PFD achieved lower FIM scores yet maintained similar motor-FIM gains compared with patients with NPFD.

Conclusions

Our study results supports the inclusion of patients with PFD in postfracture rehabilitation programs.
Can biomarkers improve the rational use of antibiotics?
Authors: Fontela Patricia S. , O’Donnell Shauna , Papenburg Jesse
Published: May 2018

Purpose of review

We aim to review recent literature about the use of biomarkers to guide the initiation and duration of antibiotic treatments for suspected bacterial infections.

Recent findings

Several good quality meta-analyses show that procalcitonin can be safely used to guide antibiotic-related decisions, especially for respiratory infections, thereby decreasing unnecessary antibiotic exposure. Furthermore, the use of CRP-based algorithms to guide antibiotic initiation in primary care patients with acute respiratory infections is associated with a reduction in antibiotic use without an increase in adverse events. Regarding neutrophil CD64 and serum amyloid A, more good-quality evidence is needed to assess their utility as biomarkers to tailor antibiotic use. Finally, transcriptomics, metabolomics and proteomics are promising tools for the development of tests to differentiate specific host responses to viral, bacterial and noninfectious stimuli, but such tests still need further validation.

Evidence shows that the use of biomarkers, procalcitonin and CRP, can safely reduce unnecessary antibiotic prescriptions in certain infectious syndromes. The clinical utility of host-based strategies such as transcriptomics, metabolomics and proteomics for the diagnosis of infectious diseases has yet to be evaluated, as well as considerations such as costs, technical complexity and result turnaround time.
Local Injections of Tacrolimus-loaded Hydrogel Reduce Systemic Immunosuppression-related Toxicity in Vascularized Composite Allotransplantation
Authors: Dzhonova Dzhuliya V. , Olariu Radu , Leckenby Jonathan , Banz Yara , Prost Jean-Christophe , Dhayani Ashish , Vemula Praveen K. , Voegelin Esther , Taddeo Adriano , Rieben Robert
Published: May 2018

Background

Routine application of vascularized composite allotransplantation is hampered by immunosuppression-related health comorbidities. To mitigate these, we developed an inflammation-responsive hydrogel for local immunosuppression. Here, we report on its long-term effect on graft survival, immunological, and toxicological impact.

Methods

Brown Norway-to-Lewis rat hindlimb transplantations were treated either systemically with daily injections of 1 mg/kg tacrolimus (TAC) or with subcutaneous intragraft injections of hydrogel containing 7 mg TAC, every 70 days. Animals were monitored for rejection or other pathology for 280 days. Systemic and graft TAC levels, regulatory T cells, and donor cell chimerism were measured periodically. At endpoint, markers for kidney, liver, and metabolic state were compared to naive age-matched rats.

Results

Both daily systemic TAC and subcutaneous intragraft TAC hydrogel at 70-day intervals were able to sustain graft survival longer than 280 days in 5 of 6 recipients. In the hydrogel group, 1 graft progressed to grade 3 rejection at postoperative day 149. In systemic TAC group, 1 animal was euthanized due to lymphoma on postoperative day 275. Hydrogel treatment provided stable graft and reduced systemic TAC levels, and a 4 times smaller total TAC dose compared with systemic immunosuppression. Hydrogel-treated animals showed preserved kidney function, absence of malignancies or opportunistic infections and increased hematopoietic chimerism compared with systemic immunosuppression.

Conclusions

Our findings demonstrate that localized immunosuppression with TAC hydrogel is a long-term safe and reliable treatment. It may reduce the burden of systemic immunosuppression in vascularized composite allotransplantation, potentially boosting the clinical application of this surgical intervention.
Dynamic Preictal Discharges in Patients With Mesial Temporal Lobe Epilepsy
Authors: Chen Jia , Li Liping , Wu Dongyan , Li Xiaoxuan , Xue Qing , Wang Liying , Du Jialin , Wang Di , Hu Minjing , Ren Liankun , Wang Yuping
Published: May 2018

Purpose:

It has been challenging to detect early changes preceding seizure onset in patients with epilepsy. This study investigated the preictal discharges (PIDs) by intracranial electroencephalogram of 11 seizures from 7 patients with mesial temporal lobe epilepsy.

Methods:

The EEG segments consisting of 30 seconds before ictal onset and 5 seconds after ictal onset were selected for analysis. After PID detection, the amplitude and interval were measured. According to the timing of PID onset, the 30-second period preceding seizure onset was divided into two stages: before PID stage and PID stage. The autocorrelation coefficients during the two stages were calculated and compared.

Results:

Preictal discharge amplitude progressively increased, while PID interval gradually decreased toward seizure onset. The autocorrelation coefficients of PID channels were significantly higher during PID stage than before PID stage. There was an overlap between channels with PIDs and seizure onset channels (80.77%).

Conclusions:

Preictal discharges emerge prior to ictal event, with a dynamic change and a spatial correlation with seizure onset zone. These findings deepen our understanding of seizure generation and help early prediction and localization of seizure onset zone.
The origin of the bird's beak: new insights from dinosaur incubation periods
Authors: Yang Tzu-Ruei , Sander P. Martin
Published: May 2018

The toothless beak of modern birds was considered as an adaption for feeding ecology; however, several recent studies suggested that developmental factors are also responsible for the toothless beak. Neontological and palaeontological studies have progressively uncovered how birds evolved toothless beaks and suggested that the multiple occurrences of complete edentulism in non-avian dinosaurs were the result of selection for specialized diets. Although developmental biology and ecological factors are not mutually exclusive, the conventional hypothesis that ecological factors account for the toothless beak appears insufficient. A recent study on dinosaur incubation period using embryonic teeth posited that tooth formation rate limits developmental speed, constraining toothed dinosaur incubation to slow reptilian rates. We suggest that selection for tooth loss was a side effect of selection for fast embryo growth and thus shorter incubation. This observation would also explain the multiple occurrences of tooth loss and beaks in non-avian dinosaur taxa crownward of
Tyrannosaurus
. Whereas our hypothesis is an observation without any experimental supports, more studies of gene regulation of tooth formation in embryos would allow testing for the trade-off between incubation period and tooth development.