bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activating α4β2 Nicotinic Acetylcholine Receptors Alleviates Fentanyl-induced Respiratory Depression in Rats
Authors: Ren Jun , Ding Xiuqing , Greer John J. 
Published: April 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Opioid analgesics are widely used for treatment of acute, postoperative, and chronic pain. However, activation of opioid receptors can result in severe respiratory depression. There is an unmet clinical need to develop a pharmacologic therapy to counter opioid-induced respiratory depression without interfering with analgesia. Further, additional advances to confront accidental lethal overdose with the use of fentanyl and other opioids are needed. Here, the authors test the hypothesis that activation of nicotinic receptors expressed within respiratory rhythm–generating networks would counter opioid-induced respiratory depression without compromising analgesia.

Methods
Respiratory neural discharge was measured using in vitro brainstem–spinal cord and medullary slice rat preparations. In vivo, plethysmographic recording, nociception testing, and righting reflexes were used to examine respiratory ventilation, analgesia, and sedation, respectively.

Results
The administration of nicotine, selective α4β2 nicotinic receptor agonist A85380, but not α7 nicotinic receptor agonist PNU282987, reversed opioid-induced respiratory depression in neonatal pups in vitro and in vivo. In adult rats in vivo, administration of A85380 (0.03 mg/kg), but not PNU282987, provides a rapid and robust reversal of fentanyl-induced decrease in respiratory rate (93.4 ± 33.7% of control 3 min after A85380 vs. 31 ± 20.5% of control after vehicle, n = 8 each, P < 0.001), without marked side effects. The coadministration of A85380 (0.06 mg/kg) with fentanyl or remifentanil markedly reduced respiratory depression and apneas, and enhanced the fentanyl-induced analgesia, as evidenced by increased paw withdrawal latency in Hargreaves plantar test (14.4 ± 2.8 s vs. vehicle: 11.3 ± 2.4 s, n = 8 each, P = 0.013) and decreased formalin-induced nocifensive duration (2.5 ± 2.4 min vs. vehicle: 5.4 ± 2.7 min, n = 8 each, P = 0.029).

Conclusions
The novel strategy of targeting α4β2 nicotinic acetylcholine receptors has the potential for advancing pain control and reducing opioid-induced respiratory depression and overdose.
Synchrotron Radiation-Based Reconstruction of the Human Spiral Ganglion: Implications for Cochlear Implantation
Authors: Li Hao , Schart-Morén Nadine , Rohani Seyed Alireza , Ladak Hanif M. , Rask-Andersen Helge , Agrawal Sumit 
Published: April 2019

Objective:
To three-dimensionally reconstruct Rosenthal’s canal (RC) housing the human spiral ganglion (SG) using synchrotron radiation phase-contrast imaging (SR-PCI). Straight cochlear implant electrode arrays were inserted to better comprehend the electro-cochlear interface in cochlear implantation (CI).

Design:
SR-PCI was used to reconstruct the human cochlea with and without cadaveric CI. Twenty-eight cochleae were volume rendered, of which 12 underwent cadaveric CI with a straight electrode via the round window (RW). Data were input into the 3D Slicer software program and anatomical structures were modeled using a threshold paint tool.

Results:
The human RC and SG were reproduced three-dimensionally with artefact-free imaging of electrode arrays. The anatomy of the SG and its relationship to the sensory organ (Corti) and soft and bony structures were assessed.

Conclusions:
SR-PCI and computer-based three-dimensional reconstructions demonstrated the relationships among implanted electrodes, angular insertion depths, and the SG for the first time in intact, unstained, and nondecalcified specimens. This information can be used to assess stimulation strategies and future electrode designs, as well as create place-frequency maps of the SG for optimal stimulation strategies of the human auditory nerve in CI.
Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV
Authors: Waalewijn Hylke , Turkova Anna , Rakhmanina Natella , Cressey Tim R. , Penazzato Martina , Colbers Angela , Burger David M. ,   on behalf of the Pediatric Antiretroviral Working Group (PAWG)
Published: April 2019

Introduction:
This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children.

Methods:
A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration–time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied.

Discussion and conclusion:
Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.
Hospital risk-based payments and physician employment: Impact on financial performance
Authors: Bazzoli Gloria J. 
Published: April 2019

Background
Hospital involvement in risk-based payment and employment of physicians can have a large impact on their profitability. Risk-based reimbursement approaches with third-party payers and provider-sponsored insurance products hold hospital organizations financially accountable for a range of patient services. Direct employment of physicians can add new revenue sources for the hospital but comes at the high cost of physician compensation packages.

Purpose
Risk bearing and physician employment have multifaceted effects on hospital profitability. The objective of this study is to assess overall financial implications of these arrangements.

Methodology
Fixed-effects estimation with American Hospital Association, Centers for Medicare & Medicaid Services, and Area Health Resource File data are used for the period 2012–2015. Key measures include indicators of hospital involvement in risk-based payments and the number of employed physicians by specialty. Hospital and market factors that could affect profitability are controlled in the analysis.

Results
Increases in employed hospitalists for hospitals with risk-based payment arrangements had a beneficial effect on their profitability. No significant association existed between profits and increased physician employment for hospitals lacking such payment arrangements and for increased nonhospitalist physician employment in hospitals with these arrangements.

Conclusions
Hospitals that hold some degree of financial responsibility for patient care have learned how to deploy employed hospitalists to their financial advantage. The unique role of hospitalists in expediting and coordinating patient care may yield the cost control that hospitals need to succeed under risk-based payment arrangements.

Practice Implications
Hospitals are still on a learning curve in determining how to structure incentives for their nonhospitalist employed physicians. To the extent that employment of these nonhospitalist physicians has not yet had a detrimental effect on hospital profits, a window of opportunity exists for hospitals to develop enhanced approaches to align primary care and specialist physicians to achieve financial aims.
It’s how we communicate! Exploring face-to-face versus electronic communication networks in multidisciplinary teams
Authors: Mascia Daniele , Rinninella Emanuele , Pennacchio Nicola Walter , Cerrito Lucia , Gasbarrini Antonio 
Published: April 2019

Background
Previous research suggests that multidisciplinary team communication networks enhance knowledge exchange, learning, and quality of care in health organizations. However, little is known about team members’ reliance on face-to-face versus electronic-based communication networks for information and knowledge exchange.

Purpose
The aim of the study was to describe patterns of face-to-face versus electronic-based communication networks in a multidisciplinary team and to explore the relationships between team communication networks and performance, measured as promptness of treatment implementation.

Methodology
We collected data on work-based communication among members of a multidisciplinary tumor board (MDT) in a large Italian research hospital. A social network survey was administered in 2016 to all board members to gather network data on face-to-face interaction and the use of electronically based communication channels (e-mail, text messages, and WhatsApp) for sharing clinical knowledge. Twenty physicians (71%) completed the survey. Archival data were accessed to obtain detailed information about 222 clinical cases discussed over a 1-year period during weekly MDT meetings. Minutes of board meetings were used to link all discussed cases to team members. We used the multiple regression quadratic assignment procedure (MR-QAP) to study associations between team member characteristics and communication networks. Negative binomial regression was employed to test relationships between team communication networks and performance.

Results
MDT members relied on different communication channels for knowledge sharing. The geographical proximity of team members positively predicted the frequency of face-to-face interaction. Physicians’ seniority was related to the use of WhatsApp as a communication channel; greater interaction of this type was observed between team members of different seniority. Performance was related positively to face-to-face communication networks but negatively to communication via WhatsApp.

Practice Implications
Although team communication networks are important for knowledge exchange, health administrators must pay attention to the increasing propensity of team members to rely on electronic-based communication. The use of these easy-to-use tools can hinder the quality of group discussion and debate.
EHA Research Roadmap on Hemoglobinopathies and Thalassemia: An Update
Authors: Iolascon Achille , De Franceschi Lucia , Muckenthaler Martina , Taher Ali , Rees David , de Montalembert Mariane , Rivella Stefano , Eleftheriou Androulla , Cappellini Maria Domenica 
Published: April 2019

AbstractThe inherited disorders of hemoglobin, which include sickle cell disease and thalassemias, are the most common and widespread distributed monogenic disorders. Due to a selective advantage in malaria regions, these hemoglobin defects are particularly frequent in Africa, Asia, or in the Mediterranean areas, where malaria was endemic until the last century. In recent decades, the globalization of migration has contributed to generate multiethnic European societies. Due to migration from countries or regions with high hemoglobinopathy frequencies such as Africa, Middle East, or Asia, large numbers of patients with these disorders are living in almost every European country today. Furthermore, the numbers are increasing because of increasing refugee flows toward Europe. Additional requirements are the development of European recommendations and guidelines for diagnosis and effective therapeutic approaches. These, together with the advancement of clinical trials using new drugs and therapeutic procedures could ameliorate the quality of life of patients affected with these diseases and increase their life expectancy. Lastly, coordinated efforts should be made to develop diagnostic pathways for thalassemias and hemoglobinopathies, in order to plan interventions, including prenatal diagnosis and cure. For these reasons, the development of new tools to reliably diagnose anemias is urgently needed and fits well with the needs of personalized medicine. In the last 15 years, hematology research has made many big leaps forward. Our general aim will be to solve several hematologic problems using these new approaches. We expect that the development of such a diagnostic tool will improve timely diagnosis throughout Europe, especially in those countries where it is difficult to gain access to “classical” diagnostic tests.
Factors That Influence the Success of Contact Lens Fitting in Presbyopes: A Multicentric Survey
Authors: Zeri Fabrizio , Di Censi Manuele , Livi Stefano , Ercoli Antonio , Naroo Shehzad A. 
Published: April 2019

Objectives:
To evaluate the key factors behind successful and unsuccessful wear of contact lenses (CLs) for patients with presbyopia.

Method:
A multicenter survey was conducted using a questionnaire, in eight CL centers, among two groups of presbyopes: successful wearers (SWs), who were presbyopic and wearing CLs successfully, and unsuccessful wearers (UWs), who tried unsuccessfully to wear CLs to manage their presbyopia and had stopped wearing CLs.

Results:
A total of 237 completed questionnaires were returned; 178 from SWs and 59 from UWs. Successful wearers used CLs 5.8±1.5 days a week and additional reading spectacles were never used by half of the SWs. Among SWs, the most important reason to continue wearing CLs was convenience (61%), whereas among UWs, the most important reason to discontinue wearing CLs was poor vision (80%). A logistic regression analysis showed that the absence of astigmatism (P<0.05), a higher subjective satisfaction (P<0.05), a better subjective perceived vision at distance (P<0.01), and a lower subjective loss of visual contrast (P<0.05) were able to predict the success of CL use for presbyopia.

Conclusions:
This study explores the predictors for determining successful or unsuccessful CL wear in presbyopes. Among ophthalmic, demographic, lifestyle, and subjective variables, the latter seems to be of greater importance in determining the success of CL wear. Therefore, it is necessary that subjective variables are taken into account by the CL practitioner when approaching presbyopic CL fitting in practice.
Correlation Between Anterior Corneal Elevation Differences in Main Meridians and Corneal Astigmatism
Authors: Batres Laura , Piñero David , Carracedo Gonzalo 
Published: April 2019

Purpose:
To assess the correlation between anterior corneal elevation (ACE) and anterior corneal astigmatism (ACA) obtained with two different topographers in healthy subjects at different corneal diameters.

Methods:
A retrospective, comparative, and observational study was conducted. Topography data from 305 patients obtained with the Oculus Pentacam (Oculus, Wetzlar, Germany) and Sirius (CSO, Florence, Italy) systems were collected. Subjects were divided into four groups depending on the magnitude of ACA. The ACE was evaluated in the principal meridians at 2, 3, and 4 mm from the corneal apex. The difference in ACE between meridians (ACE-M) and in superior–inferior and nasal–temporal semimeridians (ACE-SM) was calculated.

Results:
A strong positive correlation between ACE-M and ACA with both topographers was found for all corneal diameters (P<0.001). A linear equation to calculate the ACE-M differences as a function of the astigmatism at 8 mm of diameter was obtained: y=23.417x+1.40, where y is ACE-M in microns and x is ACA in diopters. Significant differences in ACE along SM were found for all groups studied according to the magnitude of ACA for the horizontal SM (P>0.001). The temporal meridian was more elevated at 4- and 6-mm diameters, and the nasal semimeridian was the most elevated for 8 mm.

Conclusion:
Anterior corneal astigmatism and elevation differences are strongly correlated, providing more corneal topography knowledge that could be applied in the contact lens fitting. A toric orthokeratology lens may be indicated in ACA greater than 0.75 D.
Zone of Clear Single Binocular Vision in Myopic Orthokeratology
Authors: Gifford Kate L. , Gifford Paul , Hendicott Peter L. , Schmid Katrina L. 
Published: April 2019

Purpose:
To examine the zone of clear single binocular vision (ZCSBV) in myopic children and young adults after 12 months of orthokeratology (OK) wear, in comparison with single-vision soft contact lens (SCL) wear.

Methods:
Twelve children (8–16 years) and 8 adults (18–29 years) were assessed with a series of near-point binocular vision tests when myopia was corrected using single-vision SCLs and again after 1 and 12 months of OK wear, and axial length was measured. The ZCSBV was constructed for baseline SCL wear and after 12 months of OK wear.

Results:
After 1 month of OK wear, increased accommodative responses were noted in children (C) and adults (A) as increased binocular amplitude (C:P=0.03, A:P=0.04) and reduced accommodative lag (C:P=0.01, A:P=0.01). Divergence reserves improved after 1 month in both groups (P<0.04), and a near exophoric shift was evident at 12 months (C:P=0.01, A:P=0.04). All changes at 1 month maintained stability at 12 months. An increase in accommodation and vergence responses without reduction in range resulted in an expansion of the ZCSBV in both age groups. Axial length did not significantly change in either children (P=0.25) or adults (P=0.72).

Conclusion:
In both pediatric and young adult myopes, the ZCSBV expands toward a more divergent, increased accommodation response in OK compared with SCL wear. This occurs without a corresponding loss of convergence or accommodation deactivation, indicating improved depth of focus. These findings are relevant to visual acceptance and possible mechanisms of OK's efficacy for myopia control.
Imaging vs quantitative sensory testing to predict chronic pain treatment outcomes
Authors: Davis Karen D. 
Published: April 2019

Abstract
In this article, I review the concept of personalized pain management and consider how brain imaging and quantitative sensory testing can be used to derive biomarkers of chronic pain treatment outcome. I review how different modalities of brain imaging can be used to acquire information about brain structure and function and how this information can be linked to individual measures of pain.
New approach for investigating neuropathic allodynia by optogenetics
Authors: Tsuda Makoto 
Published: April 2019

Abstract
Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. Recent studies using an optogenetic approach have shown that activation of LTMRs, including Aβ fibers that genetically express channelrhodopsin-2, by illuminating blue light to the skin elicit morphine-resistant withdrawal behaviors after nerve damage. Whole-cell recording has revealed that optical Aβ stimulation after nerve injury causes excitation of lamina I dorsal horn neurons, which are normally silent by this stimulation. Moreover, Aβ stimulation after nerve injury results in activation of central amygdaloid neurons and produces aversive behaviors. In summary, these findings indicate that optogenetics is a powerful approach for investigating LTMR-derived pain (resembling mechanical allodynia) with sensory and emotional features after nerve injury and for discovering novel and effective drugs to treat neuropathic pain.
Translational neuropathic pain research
Authors: Attal Nadine , Bouhassira Didier 
Published: April 2019

Abstract
The traditional translational approach in neuropathic pain research has mainly consisted to date in translating basic findings from animal models of nerve injury to the clinic. Because of the difficulty to extrapolate mechanisms from animals to humans, an inverse translational approach (“top–down”) has been advocated and contributed to the development of therapy. In particular, a number of treatments such as neurostimulation techniques have been initially assessed in patients and then translated to animal models for further investigation of their mechanisms. Therapeutic approaches based on an in-depth assessment of sensory phenotypes, suggestive of mechanisms, have also been implemented. The biggest trend in recent translational research is to investigate mechanisms or predict therapeutic response in patients by integrating multimodal approaches. The present narrative review emphasizes these various aspects of translational research in neuropathic pain.
Deconstructing biomarkers for chronic pain: context- and hypothesis-dependent biomarker types in relation to chronic pain
Authors: Reckziegel Diane , Vachon-Presseau Etienne , Petre Bogdan , Schnitzer Thomas J. , Baliki Marwan N. , Apkarian A. Vania 
Published: April 2019

Abstract
This review expounds on types and properties of biomarkers for chronic pain, given a mechanistic model of processes underlying development of chronic pain. It covers advances in the field of developing biomarkers for chronic pain, while outlining the general principles of categorizing types of biomarkers driven by specific hypotheses regarding underlying mechanisms. Within this theoretical construct, example biomarkers are described and their properties expounded. We conclude that the field is advancing in important directions and the developed biomarkers have the potential of impacting both the science and the clinical practice regarding chronic pain.
Structure–function relationships in peripheral nerve contributions to diabetic peripheral neuropathy
Authors: Frank Tessa , Nawroth Peter , Kuner Rohini 
Published: April 2019

Abstract
Diabetes mellitus (DM) is a major global health concern, affecting more than 9% of the world population. The most common complication of DM is diabetic peripheral neuropathy (DPN), which leads to neuropathic pain in as many as 50% of patients. Despite its prevalence, there is neither good prevention of nor treatments for DPN, representing a major gap in care for the many who are afflicted. It has long been known from patient studies that both small and large primary afferent fibers undergo structural changes in DPN; however, the exact functional contributions of these changes to DPN symptomology are unknown, necessitating animal studies. This review first presents the commonly used mouse models of DPN resulting from both type 1 and type 2 DM. It then discusses structural changes in Aβ, Aδ, and C fibers throughout the progression of DPN and their respective contributions to painful DPN in both human patients and DM mouse models. Finally, it highlights remaining questions on sensory neuron structure–function relationships in painful DPN and how we may address these in mouse models by using technological advances in cell-specific modulation. Only when these structure–function relationships are understood, can novel targeted therapeutics be developed for DPN.