bluuebunny/crossref_metadata_2025 huggingface dataset:
The diversification of begomovirus populations is predominantly driven by mutational dynamics
Authors: Lima Alison T. M. , Silva José C. F. , Silva Fábio N. , Castillo-Urquiza Gloria P. , Silva Fabyano F. , Seah Yee M. , Mizubuti Eduardo S. G. , Duffy Siobain , Zerbini F. Murilo
Published: February 2017

Begomoviruses (single-stranded DNA plant viruses) are responsible for serious agricultural threats. Begomovirus populations exhibit a high degree of within-host genetic variation and evolve as quickly as RNA viruses. Although the recombination-prone nature of begomoviruses has been extensively demonstrated, the relative contribution of recombination and mutation to the genetic variation of begomovirus populations has not been assessed. We estimated the genetic variability of begomovirus datasets from around the world. An uneven distribution of genetic variation across the length of the cp and rep genes due to recombination was evident from our analyses. To estimate the relative contributions of recombination and mutation to the genetic variability of begomoviruses, we mapped all substitutions over maximum likelihood trees and counted the number of substitutions on branches which were associated with recombination (ηr) and mutation (ημ). In addition, we also estimated the per generation relative rates of both evolutionary mechanisms (r/μ) to express how frequently begomovirus genomes are affected by recombination relative to mutation. We observed that the composition of genetic variation in all begomovirus datasets was dominated by mutation. Additionally, the low correlation between the estimates indicated that the relative contributions of recombination and mutation are not necessarily a function of their relative rates. Our results show that, although a considerable fraction of the genetic variation levels could be assigned to recombination, it was always lower than that due to mutation, indicating that the diversification of begomovirus populations is predominantly driven by mutational dynamics.
Programmed Intermittent Epidural Boluses for Maintenance of Labor Analgesia: An Impact Study
Authors: McKenzie C.P. , Cobb B. , Riley E.T. , Carvalho B.
Published: February 2017

(IJOA. 2016;26:32–38)

Maintenance of epidural labor analgesia has evolved from manual boluses to continuous infusions to patient-controlled boluses. Patient-controlled epidural analgesia (PCEA) in the presence or absence of a background continuous epidural infusion (CEI) is a common technique for providing labor analgesia. Programmed intermittent epidural bolus (PIEB) is an automated technique that provides fixed boluses of local anesthetic with or without opioid at scheduled intervals. It can be used as an alternative to CEI alone or CEI with PCEA. This current study aimed to compare PIEB+PCEA administration to CEI+PCEA administration for labor analgesia. The hypothesis was that PIEB would reduce the number of patients requiring clinician boluses compared to CEI.
US Term Stillbirth Rates and the 39-Week Rule: A Cause for Concern?
Authors: Nicholson James M. , Kellar Lisa C. , Ahmad Shahla , Abid Ayesha , Woloski Jason , Hewamudalige Nadine , Henning George F. , Lauring Julianne R. , Ural Serdar H. , Yaklic Jerome L.
Published: February 2017

(Am J Obstet Gynecol. 2016;214(5):621.e1–621.e9)

The restriction of the use of “elective” delivery before 39 weeks 0 days of gestation, known as “the 39-week rule” or “the Rule,” was mandated in 2010 in the United States. The Rule was applicable to both labor induction and prelabor cesarean delivery, and was developed as higher rates of adverse childbirth outcomes, including infant morbidity and mortality, subsequent to deliveries that occurred before 39 weeks 0 days of gestation had been reported. However, the prospective risk of term stillbirth was known to increase as a function of increasing gestational age, and hence it was speculated that the Rule might increase the overall rate of term stillbirth. This study aimed to determine whether the term stillbirth rate increased during the 7-year period that the 39-week rule was adopted. The number of live births and the number of stillbirths that occurred within each week of gestational age at and further than 37 weeks were obtained from the state health departments for the years 2007 to 2013. The patterns of the timing of term childbirth and term stillbirth were determined as a function of calendar year and gestational age for each state and for the United States overall. The number needed to treat, which represented the number of women who would need to have an early-term delivery without an accepted indication to prevent one term stillbirth, was estimated based on the change in the proportion of deliveries that occurred before the 39th week of gestation in 2013 compared with 2007, and by the estimated change in the incidence of term stillbirth that occurred in 2013 compared with 2007.
Local Anesthetic Systemic Toxicity: Continuing Professional Development
Authors: El-Boghdadly Kariem , Chin Ki Jinn
Published: February 2017

(Can J Anaesth. 2016;63(3):330–349)

Local anesthetic systemic toxicity (LAST) is a life-threatening complication that must be considered whenever local anesthetic is administered. Research has shown that with the use of ultrasound guidance and the development of new techniques, such as tissue plane blocks and local infiltration analgesia, the incidence of LAST is relative rare.
Twin Birth Study: 2-Year Neurodevelopmental Follow-up of the Randomized Trial of Planned Cesarean or Planned Vaginal Delivery for Twin Pregnancy
Authors: Asztalos Elizabeth V. , Hannah Mary E. , Hutton Eileen K. , Willan Andrew R. , Allen Alexander C. , Armson B. Anthony , Gafni Amiram , Joseph K.S. , Ohlsson Arne , Ross Susan , Sanchez J. Johanna , Mangoff Kathryn , Barrett Jon F.R.
Published: February 2017

(Am J Obstet Gynecol. 2016;214:371.e1–371.e19)

Twin pregnancies occur more often and present with complications in 2% to 3% of all deliveries. Earlier studies reporting reduced risk of adverse perinatal outcomes for one or both twins when delivered by elective cesarean delivery has led to increased rates of elective cesarean delivery. The Twin Birth Study, a randomized controlled trial, enrolled women with twin pregnancies to planned cesarean or planned vaginal deliveries. Primary analysis revealed that cesarean delivery did not alter the risk of fetal or neonatal death as compared to vaginal delivery. The secondary outcome was a combination of death or neurodevelopmental delay of the children at 2 years of age. This study presented the 2-year outcomes of the children in the Twin Birth Study.
Accidental Dural Puncture and Postdural Puncture Headache: What Are Our Options?
Authors: Van de Velde M.
Published: February 2017

(Reg Anesth Pain Med. 2016;41(2):121–122)

Accidental dural puncture (ADP) and consequent postdural puncture headache (PDPH) in obstetric patients are a cause for concern as the latter is associated with mortality and morbidity.
Trial of Labor in Twin Pregnancies: A Retrospective Cohort Study
Authors: de Castro H. , Haas J. , Schiff E. , Sivan E. , Yinon Y. , Barzilaya E.
Published: February 2017

(BJOG. 2016;123:940–945)

Retrospective studies on vaginal deliveries for twin pregnancies have reported greater fetal risk, primarily for the second twin, than cesarean deliveries. The Twin Birth Study was a recent prospective, randomized study that assigned women to planned vaginal or cesarean delivery. It assessed the success rate and safety of vaginal delivery compared with cesarean delivery among a total of 2804 twin pregnancies. This study found that both delivery modes were equally safe; however, 43.8% of women in the planned vaginal delivery group ultimately delivered by cesarean section. The current investigators analyzed the success rate of trial of labor for twin pregnancies at their tertiary care medical center in Israel.
Invasive Therapies for Primary Postpartum Haemorrhage: A Population-based Study in France
Authors: Kayem G. , Dupont C. , Bouvier-Colle M.H. , Rudigoz R.C. , Deneux-Tharaux C.
Published: February 2017

(BJOG. 2016;123:598–605)

Despite continuing improvements in obstetric practice, hemorrhage remains a major cause of maternal mortality even in developed countries.
Induction of Labour at Term With Oral Misoprostol Versus a Foley Catheter (PROBAAT-II): A Multicentre Randomized Controlled Noninferiority Trial
Authors: Ten Eikelder Mieke L.G. , Rengerink Katrien O. , Jozwiak Marta , de Leeuw Jan W. , de Graaf Irene M. , van Pampus Mariëlle G. , Holswilder Marloes , Oudijk Martijn A. , van Baaren Gert-Jan , Pernet Paula J.M. , Bax Caroline , van Unnik Gijs A. , Martens Gratia , Porath Martina , van Vliet Huib , Rijnders Robbert J.P. , Feitsma A.H. , Roumen Frans J.M.E. , van Loon Aren J. , Versendaal Hans , Weinans Martin J.N. , Woiski Mallory , van Beek Erik , Hermsen Brenda , Mol Ben Willem , Bloemenkamp Kitty W.M.
Published: February 2017

(Lancet. 2016;387:1619–1628)

When conditions pose a threat to mother or baby, obstetric interventions, including induction of labor, are required.
Judicious Use of Oxytocin Augmentation for the Management of Prolonged Labor
Authors: Rossen Janne , Østborg Tilde B. , Lindtjørn Elsa , Schulz Jørn , Eggebø Torbjørn M.
Published: February 2017

(Acta Obstet Gynecol Scand. 2016;95(3):355–361)

The use of oxytocin plays an important role in the management of labor.
The Impact of Gestational Age and Fetal Weight on the Risk of Failure of Spinal Anesthesia for Cesarean Delivery
Authors: Adesope O.A. , Einhorn L.M. , Olufolabi A.J. , Cooter M. , Habib A.S.
Published: February 2017

(IJOA. 2016;26:8–14)

The spread of spinal anesthesia may be increased during pregnancy, and hence pregnant women are considered to need a smaller dose of local anesthetic than nonpregnant women to achieve the same spinal block level. Data on spinal dosing for preterm (<37 wk of gestation) versus term (≥37 wk of gestation) parturients is limited. One earlier study found that standard doses of hyperbaric bupivacaine used for cesarean delivery failed to provide as high of a spinal block in women with preterm gestations compared to women at term. The aim of this study was to investigate the hypothesis that preterm gestation was associated with an increased risk of failed spinal anesthesia for cesarean delivery when compared with term gestation.
Effect of Preoperative Pregabalin on Postcaesarean Delivery Analgesia: A Dose-response Study
Authors: El Kenany S. , El Tahan M.R.
Published: February 2017

(IJOA. 2016;26:24–31)

Analgesia after cesarean delivery is especially important to promote early mobilization, thereby allowing the mother to care for her infant.
Expecting the Unexpected: Perspectives on Stillbirth and Late Termination of Pregnancy for Fetal Anomalies
Authors: DiMiceli-Zsigmond Mary , Williams Amanda K. , Richardson Michael G.
Published: February 2017

(Anesth Analg. 2015;121:457–464)

Stillbirth or diagnosis of a life-limiting fetal anomaly is often a traumatic experience for mothers (6 and 3 in 1000 mothers, respectively), who may experience “insufferably hard” or “emotionally straining” peripartum periods. In these cases, there is a need for the obstetric anesthesiologist to deliver empathic, supportive care that promotes the psychological recovery of the patient. In this article, the authors described 2 relevant cases and reviewed the important issues surrounding stillbirth and late termination of pregnancies for fetal anomalies.
Zika Virus Infection With Prolonged Maternal Viremia and Fetal Brain Abnormalities
Authors: Driggers R.W. , Ho C.-Y. , Korhonen E.M. , Kuivanen S. , Jääskeläinen A.J. , Smura T. , Rosenberg A. , Hill D.A. , DeBiasi R.L. , Vezina G. , Timofeev J. , Rodriguez F.J. , Levanov L. , Razak J. , Iyengar P. , Hennenfent A. , Kennedy R. , Lanciotti R. , du Plessis A. , Vapalahti O.
Published: February 2017

(N Engl J Med. 2016;374:2142–2151)

Zika virus (ZIKV), a mosquito-borne flavivirus, is associated with intrauterine or perinatal transmission and increased risk of having a newborn with microcephaly. In the present study, the authors present findings on a case of congenital ZIKV infection in a pregnancy that was terminated at 21 weeks gestation.
Evidence for Transmission of Zika Virus by Platelet Transfusion
Authors: Motta I.J. , Spencer B.R. , Cordeiro da Silva S.G. , Arruda M.B. , Dobbin J.A. , Gonzaga Y.B. , Arcuri I.P. , Tavares R.C. , Atta E.H. , Fernandes R.F. , Costa D.A. , Ribeiro L.J. , Limonte F. , Higa L.M. , Voloch C.M. , Brindeiro R.M. , Tanuri A. , Ferreira O.C.
Published: February 2017

(N Engl J Med. 2016;375:1101–1103)

In this letter to the editor, the authors discussed a report from Brazil of 2 cases of Zika virus (ZIKV) transmission by blood transfusion.
The Effect of Oral Medication on Wound Healing
Authors: Levine Jeffrey M.
Published: February 2017

GENERAL PURPOSE:

The purpose of this learning activity is to provide information about the effects of oral medications on wound healing.

TARGET AUDIENCE:

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES:

After participating in this educational activity, the participant should be better able to:

1. Identify oral medications that aid in wound healing.

2. Recognize oral medications that interfere with wound healing.

Given the accelerated medical discoveries of recent decades, there is a surprising lack of oral medications that directly improve wound healing. Of the oral medications available, most target ancillary aspects of wound care such as pain management, infection mitigation, and nutrition. This article describes oral pharmacologic agents intended to build new tissue and aid in wound healing, as well as an introduction to oral medications that interfere with wound healing. This review will not discuss the pharmacology of pain management or treatment of infection, nor will it address nutritional supplements.
Structural Failure Sites in Anterior Vaginal Wall Prolapse: Identification of a Collinear Triad
Authors: Chen Luyun , Lisse Sean , Larson Kindra , Berger Mitchell B. , Ashton-Miller James A. , DeLancey John O. L.
Published: February 2017

(Abstracted from Obstet Gynecol 2016;128:853–862)

The most common form of pelvic organ prolapse and the most frequent site of operative failure is cystocele formation (anterior vaginal wall prolapse). Potential fascial and muscular failure factors (anatomic sites of injury) identified as causal factors contributing to cystocele formation include 2 vaginal failure sites (apical support and paravaginal defects), 2 vaginal wall factors (vaginal width and length), and 2 levator ani factors (hiatus size and levator ani defects).
Fetal and Neonatal Outcomes After Term and Preterm Delivery After Betamethasone Administration in Twin Pregnancies
Authors: Braun Thorsten , Weichert Alexander , Gil Hannah C. , Sloboda Deborah M. , Tutschek Boris , Harder Thomas , Dudenhausen Joachim W. , Plagemann Andreas , Henrich Wolfgang
Published: February 2017

(Abstracted from Int J Gynaecol Obstet 2016;134:329–335)

Prenatal betamethasone administration in singleton pregnancies is associated with a dose-dependent decrease in birth weight. This study aimed to determine the effects of betamethasone overall, and at different doses on fetal growth and neonatal outcomes in twin pregnancies based on fetal sex, chorionicity, and severity of prematurity.
Understanding the Role of Religious Views in the Discussion About Resuscitation at the Threshold of Viability
Authors: McGuirl J. , Campbell D.
Published: February 2017

(Abstracted from J Perinatol 2016;36:694–698)

One of the challenges faced by neonatologists and obstetric care providers is their interaction with parents expecting the delivery of a fetus at the “threshold of viability,” between 22 weeks and 25 weeks of gestation. Conversations regarding the chances of survival, the probability of survival without disability, or the risk of moderate to severe disability are common in such situations.
Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-Term Weight Loss: The IDEA Randomized Clinical Trial
Authors: Jakicic John M. , Davis Kelliann K. , Rogers Renee J. , King Wendy C. , Marcus Marsha D. , Helsel Diane , Rickman Amy D. , Wahed Abdus S. , Belle Steven H.
Published: February 2017

(Abstracted from JAMA 2016;316(11):1161–1171)

Obesity is an increasing public health concern and is associated with several health conditions. Commercial technologies, including wearable devices, are available to monitor physical activity and diet and have been demonstrated to be moderately effective in promoting weight loss in prior studies.
Risk of Psychiatric Illness From Advanced Paternal Age Is Not Predominantly From De Novo Mutations
Authors: Gratten Jacob , Wray Naomi R. , Peyrot Wouter J. , McGrath John J. , Visscher Peter M. , Goddard Michael E.
Published: February 2017

(Abstracted from Nat Genet 2016;48:718–724)

Epidemiologic studies have reported an increased risk of schizophrenia, autism, and other psychiatric disorders among offspring of older fathers. It is widely assumed that paternal age–related de novo mutations are the primary underlying causal mechanism.
Feedback for Learners in Medical Education: What Is Known? A Scoping Review
Authors: Bing-You Robert , Hayes Victoria , Varaklis Kalli , Trowbridge Robert , Kemp Heather , McKelvy Dina
Published: February 2017

Purpose

To conduct a scoping review of the literature on feedback for learners in medical education.

Method

In 2015–2016, the authors searched the Ovid MEDLINE, ERIC, CINAHL, ProQuest Dissertations and Theses Global, Web of Science, and Scopus databases and seven medical education journals (via OvidSP) for articles published January 1980–December 2015. Two reviewers screened articles for eligibility with inclusion criteria. All authors extracted key data and analyzed data descriptively.

Results

The authors included 650 articles in the review. More than half (n = 341) were published during 2010–2015. Many centered on medical students (n = 274) or residents (n = 192); some included learners from other disciplines (n = 57). Most (n = 633) described methods used for giving feedback; some (n = 95) described opinions and recommendations regarding feedback. Few studies assessed approaches to feedback with randomized, educational trials (n = 49) or described changes in learner behavior after feedback (n = 49). Even fewer assessed the impact of feedback on patient outcomes (n = 28).

Conclusions

Feedback is considered an important means of improving learner performance, as evidenced by the number of articles outlining recommendations for feedback approaches. The literature on feedback for learners in medical education is broad, fairly recent, and generally describes new or altered curricular approaches that involve feedback for learners. High-quality, evidence-based recommendations for feedback are lacking. In addition to highlighting calls to reassess the concepts and complex nature of feedback interactions, the authors identify several areas that require further investigation.
Emergency Medical Technician Training During Medical School: Benefits for the Hidden Curriculum
Authors: Russ-Sellers Rebecca , Blackwell Thomas H.
Published: February 2017

Problem

Medical schools are encouraged to introduce students to clinical experiences early, to integrate biomedical and clinical sciences, and to expose students to interprofessional health providers and teams. One important goal is for students to gain a better understanding of the patients they will care for in the future and how their social and behavioral characteristics may affect care delivery.

Approach

To promote early clinical exposure and biomedical integration, in 2012 the University of South Carolina School of Medicine Greenville incorporated emergency medical technician (EMT) training into the curriculum. This report describes the program; outlines changes (made after year 1) to improve biomedical integration; and provides a brief analysis and categorization of comments from student reflections to determine whether particular themes, especially related to the hidden curriculum, appeared.

Outcomes

Medical students wrote frequently about EMT-related experiences: 29% of reflections in the charter year (1.2 per student) and 38% of reflections in the second year (1.5 per student) focused on EMT-related experiences. Reflections related to patient care, professionalism, systems-based practice, and communication/interpersonal skills. The frequency of themes in student reflections may provide insight into a medical program’s hidden curriculum. This information may serve to inform curricula that focus on biosocial elements such as professionalism and communication with the goal of enhancing future physicians’ tolerance, empathy, and patient-centeredness.

Next Steps

The authors plan to conduct further qualitative analysis of student reflections to iteratively revise curricula to address gaps both in learning and in the differences between the explicit curriculum and actual experiences.
Training Internal Medicine Residents in Social Medicine and Research-Based Health Advocacy: A Novel, In-Depth Curriculum
Authors: Basu Gaurab , Pels Richard J. , Stark Rachel L. , Jain Priyank , Bor David H. , McCormick Danny
Published: February 2017

Problem

Health disparities are pervasive worldwide. Physicians have a unique vantage point from which they can observe the ways social, economic, and political factors impact health outcomes and can be effective advocates for enhanced health outcomes and health equity. However, social medicine and health advocacy curricula are uncommon in postgraduate medical education.

Approach

In academic year (AY) 2012, the Cambridge Health Alliance internal medicine residency program transformed an elective into a required social medicine and research-based health advocacy curriculum. The course has three major innovations: it has a yearlong longitudinal curriculum, it is required for all residents, and all residents complete a group research-based health advocacy project within the curricular year. The authors describe the structure, content, and goals of this curriculum.

Outcomes

Over the last four years (AYs 2012–2015), residents (17/32; 53%) have rated the overall quality of the course highly (mean = 5.2, where 6 = outstanding; standard deviation = 0.64). In each year since the new course has been implemented, all scholarly work from the course has been presented at conferences by 31 resident presenters and/or coauthors. The course seems to enhance the residency program’s capacity to recruit high-caliber residents and faculty members.

Next Steps

The authors are collecting qualitative and quantitative data on the impact of the course. They will use their findings to advocate for a national health advocacy competency framework. Recommendations about how to initiate or further develop social medicine and health advocacy curricula are offered.
Interprofessional Medical–Legal Education of Medical Students: Assessing the Benefits for Addressing Social Determinants of Health
Authors: Pettignano Robert , Bliss Lisa , McLaren Susan , Caley Sylvia
Published: February 2017

Problem

Screening tools exist to help identify patient issues related to social determinants of health (SDH), but solutions to many of these problems remain elusive to health care providers as they require legal solutions. Interprofessional medical–legal education is essential to optimizing health care delivery.

Approach

In 2011, the authors implemented a four-session didactic interprofessional curriculum on medical–legal practice for third-year medical students at Morehouse School of Medicine. This program, also attended by law students, focused on interprofessional collaboration to address client/patient SDH issues and health-harming legal needs. In 2011–2014, the medical students participated in pre- and postintervention surveys designed to determine their awareness of SDH’s impact on health as well as their attitudes toward screening for SDH issues and incorporating resources, including a legal resource, to address them. Mean ratings were compared between pre- and postintervention respondent cohorts using independent-sample t tests.

Outcomes

Of the 222 medical students who participated in the program, 102 (46%) completed the preintervention survey and 100 (45%) completed the postintervention survey. Postintervention survey results indicated that students self-reported an increased likelihood to screen patients for SDH issues and an increased likelihood to refer patients to a legal resource (P < .001).

Next Steps

Incorporating interprofessional medical–legal education into undergraduate medical education may result in an increased likelihood to screen patients for SDH and to refer patients with legal needs to a legal resource. In the future, an additional evaluation to assess the curriculum’s long-term impact will be administered prior to graduation.
Proposing a Model of Co-Regulated Learning for Graduate Medical Education
Authors: Rich Jessica V.
Published: February 2017

Primarily grounded in Zimmerman’s social cognitive model of self-regulation, graduate medical education is guided by principles that self-regulated learning takes place within social context and influence, and that the social context and physical environment reciprocally influence persons and their cognition, behavior, and development. However, contemporary perspectives on self-regulation are moving beyond Zimmerman’s triadic reciprocal orientation to models that consider social transactions as the central core of regulated learning. Such co-regulated learning models emphasize shared control of learning and the role more advanced others play in scaffolding novices’ metacognitive engagement.

Models of co-regulated learning describe social transactions as periods of distributed regulation among individuals, which instrumentally promote or inhibit the capacity for individuals to independently self-regulate. Social transactions with other regulators, including attending physicians, more experienced residents, and allied health care professionals, are known to mediate residents’ learning and to support or hamper the development of their self-regulated learning competence. Given that social transactions are at the heart of learning-oriented assessment and entrustment decisions, an appreciation for co-regulated learning is likely important for advancing medical education research and practice—especially given the momentum of new innovations such as entrustable professional activities.

In this article, the author explains why graduate medical educators should consider adopting a model of co-regulated learning to complement and extend Zimmerman’s models of self-regulated learning. In doing so, the author suggests a model of co-regulated learning and provides practical examples of how the model is relevant to graduate medical education research and practice.
Lipids and lipid changes with synthetic and biologic disease-modifying antirheumatic drug therapy in rheumatoid arthritis: implications for cardiovascular risk
Authors: Myasoedova Elena
Published: February 2017

Purpose of review

To highlight recently published studies addressing lipid changes with disease-modifying antirheumatic drug use and outline implications on cardiovascular outcomes in rheumatoid arthritis (RA).

Recent findings

Growing evidence suggests lower lipid levels are present in patients with active RA vs. general population, and significant modifications of lipid profile with inflammation suppression. Increase in lipid levels in patients with RA on synthetic and biological disease-modifying antirheumatic drugs may be accompanied by antiatherogenic changes in lipid composition and function. The impact of lipid changes on cardiovascular outcomes in RA is a subject of active research. The role of lipids in cardiovascular risk in RA may be overpowered by the benefits of inflammation suppression with antirheumatic medication use. Recommendations on lipid management in RA are evolving but uncertainty exists regarding frequency of lipid testing and goals of treatment.

Knowledge about quantitative and qualitative lipid changes in RA is expanding. The relative role of lipids in cardiovascular risk in the context of systemic inflammation and antirheumatic therapy remains uncertain, delaying development of effective strategies for cardiovascular risk management in RA. Studies are underway to address these knowledge gaps and may be expected to inform cardiovascular risk management in RA and the general population.
Recent advances in the pathogenesis, prediction, and management of rheumatoid arthritis-associated interstitial lung disease
Authors: Johnson Cheilonda
Published: February 2017

Purpose of review

To provide an overview of recently published articles covering interstitial lung disease associated with rheumatoid arthritis (RA-ILD).

Recent findings

Over the past year, many studies replicated previous findings in more diverse and occasionally larger populations internationally. Specifically, the association among cigarette smoking, high rheumatoid factor titer, elevated anticitrullinated protein antibody (ACPA) levels, and RA-ILD was strengthened. Clinical characteristics, autoantibodies, and biomarkers to aid in RA-ILD development, progression, and mortality prediction were explored. Finally, direct and indirect treatment effects were highlighted.

The ability to identify risk factors for preclinical RA-ILD has been enhanced, but the proper management strategy for these patients is yet to be defined. ACPAs and cigarette smoking are highly associated with RA-ILD, but the mechanistic relationship between lung injury and autoantibody generation remains unknown. There is conflicting evidence regarding the significance of a usual interstitial pneumonia (UIP) versus non-UIP pattern on high-resolution computed tomography. The use of biologic agents in patients with rheumatoid arthritis does not appear to increase the risk of incident ILD or RA-ILD exacerbation. Randomized prospective studies of specific therapy for RA-ILD are still lacking.
When Is a Fracture Not “Fresh”? Aligning Reimbursement With Patient Outcome After Treatment With Low-Intensity Pulsed Ultrasound
Authors: Zura Robert , Xu Zekun (Jack) , Della Rocca Gregory J. , Mehta Samir , Steen R. Grant
Published: February 2017

Objective:

The clinical value of low-intensity pulsed ultrasound (LIPUS) for fresh fracture is known. Yet, in the absence of a definition of what “fresh” is, payers have adopted study inclusion criteria drawn from randomized clinical trials as de facto definitions of which patients should be treated, with “fresh” defined as <1 week old. Patients with fracture may thus be ineligible for LIPUS treatment after week 1, which potentially denies access to patients who could benefit from LIPUS. We seek to characterize the inflection point at which heal rate declines.

Design:

Prospective cohort.

Setting:

Food and Drug Administration–mandated nationwide postmarketing surveillance registry.

Patients:

Observational cohort of 5983 registry enrollees.

Intervention:

LIPUS, 20 min/d.

Main Outcome Measure:

Fracture heal rate. Logistic regression was used to model the odds ratio of nonunion from week 1 to week 12. Covariates in the model included age, gender, body mass index, open fracture, and smoking.

Results:

We estimated the time point at which a fracture responds to LIPUS as well as during the first week after fracture. There was significant bone-to-bone variation; metatarsal was “fresh” until week 7, ankle until week 9, humerus until week 10, and femur and radius until week 12. Healing was significantly impacted by patient age, body mass index, and open fracture (all, P ≤ 0.02).

Conclusions:

Our results suggest that fractures of the metatarsal, femur, humerus, ankle, and radius respond to LIPUS treatment, as if they were still fresh at least 6 weeks longer than the eligibility allowed under current coverage policies.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
When Should We Change Drill Bits? A Mechanical Comparison of New, Reprocessed, and Damaged Bits
Authors: Myers Richard , Kim Hyunchul , Hsieh Adam H. , O'Toole Robert V. , Sciadini Marcus F.
Published: February 2017

Objectives:

We assessed how reprocessed and damaged drill bits perform relative-to-new drill bits in terms of drilling force required, heat generated at near and far cortices, and number of usable passes.

Methods:

Nine pairs of nonosteoporotic human cadaveric femora were tested using 3 types of 3.2-mm drill bits (new, reprocessed, and damaged) in 3 investigations (force, temperature, and multiple usable passes). Operating room conditions were simulated. Force and temperature data were collected for each type. The multiple pass investigation measured only force.

Results:

New and reprocessed drill bits performed similarly regarding force required and heat generated; both outperformed damaged bits. New and reprocessed bits had a similar number of usable passes in ideal conditions. Damaged bits required nearly 2.6 times as much force to maintain drilling rate.

Conclusions:

Reprocessed drill bits seem to be a viable alternative to new drill bits for fracture treatment surgery in terms of force required, heat generated, and number of usable passes. Drill bits that are damaged intraoperatively should be replaced. In ideal conditions, new and reprocessed drill bits can be used for multiple consecutive cases.

Clinical Relevance:

Reprocessed drill bits may be as effective as new drill bits, representing potential cost savings for institutions. Both types can be considered for reuse.
Gravity Stress Radiographs and the Effect of Ankle Position on Deltoid Ligament Integrity and Medial Clear Space Measurements
Authors: Ashraf Ali , Murphree Jacob , Wait Eric , Winston Travis , Wooldridge Adam , Meriwether Matthew , Wilson Joshua , Grimes Jerry S.
Published: February 2017

Introduction:

External rotation and gravity stress radiographs have been described to distinguish stable supination-external rotation-II (SER-II) ankle fractures from unstable SER-IV fractures. It has been previously shown that both external rotation and gravity stress views are equivalent in their ability to diagnose deltoid ligament injury. It has also been shown that the position of the ankle influences the external rotation stress radiograph. However, no data of ankle position exist for gravity stress radiographs.

Methods:

Eight fresh-frozen cadaveric ankles were dissected and destabilized sequentially according to the SER mechanism of ankle fractures, starting with the anterior inferior tibiofibular ligament, distal fibula osteotomy at the level of the syndesmosis, posterior inferior tibiofibular ligament, superficial deltoid ligament, and finally the deep deltoid ligament. Fluoroscopic radiographs were taken with gravity stress views in both neutral and plantarflexion. Measurements of both dorsal and the medial clear space were taken for each stage. The difference between the dorsal and medial clear space was measured.

Results:

Positive predictive value (PPV) with a medial clear space cutoff of 5 mm was 80% in plantarflexion and 72.72% in neutral with a negative predictive value (NPV) of 100% in both positions. Using a 6-mm cutoff, the PPV improved to 100% and NPV remained 100% for both neutral and plantarflexion. When the difference measurement is used, a 1.0-mm difference yielded a PPV of 72% and an NPV of 100% in both neutral and plantarflexion. With a 1.5-mm cutoff, the PPV and NPV were 100% for both positions.

Conclusions:

The position of the ankle during gravity stress radiographs does not influence the clinical effectiveness of the images. Using larger references for stability, the PPV can be improved.
Checkpoint inhibitor-associated drug reaction with eosinophilia and systemic symptom syndrome
Authors: Mirza Sayeef , Hill Ebone’ , Ludlow Steven P. , Nanjappa Sowmya
Published: February 2017

Drug reaction with eosinophilia and systemic symptom syndrome is a potentially fatal drug reaction that must be recognized quickly. Ipilimumab and nivolumab are both important agents in the treatment of melanoma and continue to be studied in other malignancies. We believe the mainstay of therapy for immunotherapy-induced drug reaction with eosinophilia and systemic symptom syndrome is early recognition, discontinuation of the inciting agent, supportive care, and treatment with high dose corticosteroids with appropriate tapers that may reduce the length of internal organ injury in cases with liver or kidney involvement.
Alzheimer’s disease in the zebrafish: where can we take it?
Authors: Caramillo Erika M. , Echevarria David J.
Published: February 2017

With the ever-growing geriatric population, research on brain diseases such as dementia is more imperative now than ever. The most prevalent of all dementias is Alzheimer’s disease, a progressive neurodegenerative disease that presents with deficits in memory, cognition, motor skills, and a general decline in the quality of life. The social and economic burden associated with Alzheimer’s disease is tremendous and is projected to grow even greater over the coming years. There is a specific need to elucidate and improve the treatments available, not only to alleviate the symptoms related to dementias such as Alzheimer’s but also to prevent the formation of the disease. This is an effort that can be expedited and made more efficient by utilizing an animal model such as the zebrafish. This paper reviews the utility of zebrafish in Alzheimer’s research by examining research on a sampling of the treatments available for the disease, specifically donepezil, memantine, and methylene blue. The human model and the shortcomings of the rodent model are also discussed.
Burn injury decreases the antinociceptive effects of opioids
Authors: Emery Michael A. , Bates M.L. Shawn , Wellman Paul J. , Eitan Shoshana
Published: February 2017

Burn victim patients are frequently prescribed opioids at doses that are significantly higher than standard analgesic dosing guidelines, and, even despite an escalation in opioid dosing, many continue to experience pain. Thus, the aim of this study was to determine the effect of burn injury on opioid antinociception. Mice were examined for their baseline pain sensitivity thresholds using the von Frey filaments test. Then, they were subjected to burn or sham injury to the dorsal surface of the hindpaw and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 following the burn injury. The antinociceptive effects of the various drugs were analyzed by computing the daily difference between pain sensitivity threshold scores (in g) before and after treatment. This study showed that burn injury decreases opioid antinociception potency. A marked reduction was observed in the antinociceptive effectiveness of all opioids, and for both doses, in the burn-injured versus the sham animals. These results suggest that burn trauma limits the ability of opioids to be effective in reducing pain.
High-fat diet alters weight, caloric intake, and haloperidol sensitivity in the context of effort-based responding
Authors: Robertson Stephen H. , Boomhower Steven R. , Rasmussen Erin B.
Published: February 2017

High-fat (HF) diets result in weight gain, hyperphagia, and reduced dopamine D2signaling; however, these findings have been obtained only under free-feeding conditions. This study tested the extent to which HF diet affects effort-dependent food procurement and the extent to which dopamine signaling is involved. Male Sprague-Dawley rats consumed either a HF (n=20) or a standard-chow (n=20) diet. We assessed the sensitivity to effort-based reinforcement in 10 rats from each group by measuring consumption across a series of fixed-ratio schedules (FR 5–FR 300) under a closed economy and quantified performance using the exponential-demand equation. For each FR, acute injections of 0 or 0.1 mg/kg of haloperidol, a D2antagonist, were administered to assess dopamine-related changes in consumption. Rats fed a HF diet consumed more calories and weighed significantly more than rats fed standard-chow. Food consumption decreased in both groups in an effort-dependent manner, but there were no group differences. Haloperidol reduced responding in an FR-dependent manner for both groups. Animals exposed to a HF diet showed an altered sensitivity to haloperidol relative to rats fed a standard diet, suggesting that HF diet alters sensitivity to DA signaling underlying effort-based food procurement.
The contribution of transgenic and nontransgenic animal models in Alzheimer’s disease drug research and development
Authors: Mhillaj Emanuela , Cuomo Vincenzo , Mancuso Cesare
Published: February 2017

Over the last few years, several papers have become available in the literature on both the main hallmarks of Alzheimer’s disease (AD) and the several intracellular pathways whose alteration is responsible for its onset and progression. The use of transgenic and nontransgenic animal models has played a key role in achieving such a remarkable amount of preclinical data, allowing researchers to dissect the cellular changes occurring in the AD brain. In addition, the huge amount of preclinical evidence arising from these animal models was necessary for the further clinical development of pharmacological agents capable of interfering with most of the impaired neural pathways in AD patients. In this respect, a significant role is played by the dysfunction of excitatory and inhibitory neurotransmission responsible for the cognitive and behavioral symptoms described in AD patients. The aim of this review is to summarize the main animal models that contributed toward unraveling the pathological changes in neurotransmitter synthesis, release, and receptor binding in AD preclinical studies. The review also provides an updated description of the current pharmacological agents – still under clinical development – acting on the neurotransmitter systems.
Prenatal imaging findings in fetal Zika virus infection
Authors: Araujo Júnior Edward , Carvalho Francisco H.C. , Tonni Gabriele , Werner Heron
Published: February 2017

Purpose of review

The aim of this review is to report the most recent observations concerning intrauterine Zika virus (ZIKV) infection and associated neuroimaging.

Recent findings

ZIKV outbreak in Brazil in 2015 was associated with an impressive registration of cases of congenital microcephaly in women with symptoms suggestive of ZIKV infection. Clinical and laboratory testing for ZIKV and hypothetic etiopathogenetic mechanisms are described. Diagnostic tests on blood, urine and amniotic fluid should be performed in all mothers with symptoms suggestive of intrauterine ZIKV infection. ZIKV causes multiple teratogenic malformations, mainly affecting the developing brain.

Neuroimaging investigation contributes to the prenatal detection of microcephaly and other brain abnormalities in cases of intrauterine ZIKV infection. Neuroimaging is based antenatally on two-dimensional and three-dimensional ultrasound and fetal MRI, whereas computed tomography scan is performed postnatally. Although neuropathology associated with intrauterine ZIKV infection is characterized by nonspecific findings of brain disorder, reduced cortical gyration and white-matter hypomyelination or dysmyelination and cerebellar hypoplasia have been consistently observed in the majority of fetuses and newborns. Prenatal or postnatal genetic workup should be carried out to exclude cases of primary microcephaly. Follow-up should rely upon MRI and computed tomography scan as well as neuropediatrician to better define developmental outcome in survivors.
Noninvasive prenatal diagnosis for single gene disorders
Authors: Allen Stephanie , Young Elizabeth , Bowns Benjamin
Published: February 2017

Purpose of review

Noninvasive prenatal diagnosis for single gene disorders is coming to fruition in its clinical utility. The presence of cell-free DNA in maternal plasma has been recognized for many years, and a number of applications have developed from this. Noninvasive prenatal diagnosis for single gene disorders has lagged behind due to complexities of technology development, lack of investment and the need for validation samples for rare disorders.

Recent findings

Publications are emerging demonstrating a variety of technical approaches and feasibility of clinical application. Techniques for analysis of cell-free DNA including digital PCR, next-generation sequencing and relative haplotype dosage have been used most often for assay development. Analysis of circulating fetal cells in the maternal blood is still being investigated as a viable alternative and more recently transcervical trophoblast cells. Studies exploring ethical and social issues are generally positive but raise concerns around the routinization of prenatal testing.

Further work is necessary to make testing available to all patients with a pregnancy at risk of a single gene disorder, and it remains to be seen if the development of more powerful technologies such as isolation and analysis of single cells will shift the emphasis of noninvasive prenatal diagnosis. As testing becomes possible for a wider range of conditions, more ethical questions will become relevant.
CHOROIDAL THICKNESS IN PATIENTS WITH STARGARDT DISEASE
Authors: Vural Esra , Acar Ugur , Sevinc Mehmet K. , Erdurmus Mesut , Kucuk Bekir , Aykas Seckin , Sobaci Gungor
Published: February 2017

Purpose:

To investigate the relationship between choroidal thicknesses (CT), central foveal thicknesses, multifocal electroretinography (mf-ERG) responses, and best-corrected visual acuity levels in patients with Stargardt disease (STGD).

Methods:

A total of 30 eyes of 30 patients with STGD, and 30 age- and sex-matched healthy controls were included in the study. All participants underwent detailed ophthalmic examination including best-corrected visual acuity and spectral domain optical coherence tomography measurements, and also patients with STGD were performed mf-ERG.

Results:

The mean subfoveal CT values were 271.95 ± 85.57 μm in patients with STGD and 355.73 ± 87.41 μm in the control group (P < 0.001). The mean central foveal thickness values were 223.56 ± 61.38 μm in patients with STGD and 272.46 ± 27.52 μm in the control group (P < 0.001). The mean central and paracentral mf-ERG responses (45.71 ± 26.60 and 16.47 ± 10.75 Nv/deg2 respectively) in patients with STGD were significantly lower from the normal ranges (66.6–130.8 Nv/deg2 and 30.9–77.7 Nv/deg2, respectively; P < 0.001 for both). There was a statistically significant correlation between subfoveal CT and best-corrected visual acuity levels (P = 0.012, r = −0.452), and between parafoveal CT and inner retinal thickness and paracentral mf-ERG responses (P = 0.043, r = +0.372 and P = 0.049, r = +0.363, respectively). Paracentral mf-ERG responses were also correlated with outer retinal thickness values (P = 0.005, r = +0.503).

Conclusion:

Patients with STGD have a thinner CT, which may be responsible for some of the clinical findings. The pathophysiological significance of these findings needs further study.