bluuebunny/crossref_metadata_2025 huggingface dataset:
Chasing Private Information
Authors: Kacperczyk Marcin , Pagnotta Emiliano S
Published: March 2019

Using over 5,000 trades unequivocally based on nonpublic information about firm fundamentals, we find that asymmetric information proxies display abnormal values on days with informed trading. Volatility and volume are abnormally high, whereas illiquidity is low, in equity and option markets. Daily returns reflect the sign of private signals, but bid-ask spreads are lower when informed investors trade. Market makers’ learning under event uncertainty and limit orders help explain these findings. The cross-section of information duration indicates that traders select days with high uninformed volume. Evidence from the U.S. SEC Whistleblower Reward Program and the FINRA involvement addresses selection concerns.

Received January 11, 2017; editorial decision December 17, 2018 by Editor Andrew Karolyi. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Shmapped: development of an app to record and promote the well-being benefits of noticing urban nature
Authors: McEwan Kirsten , Richardson Miles , Brindley Paul , Sheffield David , Tait Crawford , Johnson Steve , Sutch Hana , Ferguson Fiona J
Published: March 2019

The majority of research to date on the links between well-being and green spaces comes from cross-sectional studies. Shmapped is an app that allows for the collection of well-being and location data live in the field and acts as a novel dual data collection tool and well-being intervention, which prompts users to notice the good things about their surroundings. We describe the process of developing Shmapped from storyboarding, budgeting, and timescales; selecting a developer; drawing up data protection plans; and collaborating with developers and end-user testers to ultimately publishing Shmapped. The development process and end-user testing resulted in a highly functional app. Limitations and future uses of such novel dual data collection and intervention apps are discussed and recommendations are made for prospective developers and researchers.
Drought response strategies and hydraulic traits contribute to mechanistic understanding of plant dry-down to hydraulic failure
Authors: Blackman Chris J , Creek Danielle , Maier Chelsea , Aspinwall Michael J , Drake John E , Pfautsch Sebastian , O’Grady Anthony , Delzon Sylvain , Medlyn Belinda E , Tissue David T , Choat Brendan
Published: March 2019

Drought-induced tree mortality alters forest structure and function, yet our ability to predict when and how different species die during drought remains limited. Here, we explore how stomatal control and drought tolerance traits influence the duration of drought stress leading to critical levels of hydraulic failure. We examined the growth and physiological responses of four woody plant species (three angiosperms and one conifer) representing a range of water-use and drought tolerance traits over the course of two controlled drought–recovery cycles followed by an extended dry-down. At the end of the final dry-down phase, we measured changes in biomass ratios and leaf carbohydrates. During the first and second drought phases, plants of all species closed their stomata in response to decreasing water potential, but only the conifer species avoided water potentials associated with xylem embolism as a result of early stomatal closure relative to thresholds of hydraulic dysfunction. The time it took plants to reach critical levels of water stress during the final dry-down was similar among the angiosperms (ranging from 39 to 57 days to stemP88) and longer in the conifer (156 days to stemP50). Plant dry-down time was influenced by a number of factors including species stomatal-hydraulic safety margin (gsP90 – stemP50), as well as leaf succulence and minimum stomatal conductance. Leaf carbohydrate reserves (starch) were not depleted at the end of the final dry-down in any species, irrespective of the duration of drought. These findings highlight the need to consider multiple structural and functional traits when predicting the timing of hydraulic failure in plants.
An Anesthesiologist’s Perspective on the History of Basic Airway Management
Authors: Matioc Adrian A.
Published: March 2019

This fourth and last installment of my history of basic airway management discusses the current (i.e., “modern”) era of anesthesia and resuscitation, from 1960 to the present. These years were notable for the implementation of intermittent positive pressure ventilation inside and outside the operating room. Basic airway management in cardiopulmonary resuscitation (i.e., expired air ventilation) was de-emphasized, as the “A-B-C” (airway-breathing-circulation) protocol was replaced with the “C-A-B” (circulation-airway-breathing) intervention sequence. Basic airway management in the operating room (i.e., face-mask ventilation) lost its predominant position to advanced airway management, as balanced anesthesia replaced inhalation anesthesia. The one-hand, generic face-mask ventilation technique was inherited from the progressive era. In the new context of providing intermittent positive pressure ventilation, the generic technique generated an underpowered grip with a less effective seal and an unspecified airway maneuver. The significant advancement that had been made in understanding the pathophysiology of upper airway obstruction was thus poorly translated into practice. In contrast to consistent progress in advanced airway management, progress in basic airway techniques and devices stagnated.
α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents
Authors: Deng Meichun , Chen Shao-Rui , Chen Hong , Pan Hui-Lin
Published: March 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Chronic use of μ-opioid receptor agonists paradoxically causes both hyperalgesia and the loss of analgesic efficacy. Opioid treatment increases presynaptic N-methyl-d-aspartate receptor activity to potentiate nociceptive input to spinal dorsal horn neurons. However, the mechanism responsible for this opioid-induced activation of presynaptic N-methyl-d-aspartate receptors remains unclear. α2δ-1, formerly known as a calcium channel subunit, interacts with N-methyl-d-aspartate receptors and is primarily expressed at presynaptic terminals. This study tested the hypothesis that α2δ-1–bound N-methyl-d-aspartate receptors contribute to presynaptic N-methyl-d-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance.

Methods

Rats (5 mg/kg) and wild-type and α2δ-1–knockout mice (10 mg/kg) were treated intraperitoneally with morphine twice/day for 8 consecutive days, and nociceptive thresholds were examined. Presynaptic N-methyl-d-aspartate receptor activity was recorded in spinal cord slices. Coimmunoprecipitation was performed to examine protein–protein interactions.

Results

Chronic morphine treatment in rats increased α2δ-1 protein amounts in the dorsal root ganglion and spinal cord. Chronic morphine exposure also increased the physical interaction between α2δ-1 and N-methyl-d-aspartate receptors by 1.5 ± 0.3 fold (means ± SD, P = 0.009, n = 6) and the prevalence of α2δ-1–bound N-methyl-d-aspartate receptors at spinal cord synapses. Inhibiting α2δ-1 with gabapentin or genetic knockout of α2δ-1 abolished the increase in presynaptic N-methyl-d-aspartate receptor activity in the spinal dorsal horn induced by morphine treatment. Furthermore, uncoupling the α2δ-1–N-methyl-d-aspartate receptor interaction with an α2δ-1 C terminus–interfering peptide fully reversed morphine-induced tonic activation of N-methyl-d-aspartate receptors at the central terminal of primary afferents. Finally, intraperitoneal injection of gabapentin or intrathecal injection of an α2δ-1 C terminus–interfering peptide or α2δ-1 genetic knockout abolished the mechanical and thermal hyperalgesia induced by chronic morphine exposure and largely preserved morphine’s analgesic effect during 8 days of morphine treatment.

Conclusions

α2δ-1–Bound N-methyl-d-aspartate receptors contribute to opioid-induced hyperalgesia and tolerance by augmenting presynaptic N-methyl-d-aspartate receptor expression and activity at the spinal cord level.
Health Care Experiences of Transgender Adults
Authors: Cicero Ethan C. , Reisner Sari L. , Silva Susan G. , Merwin Elizabeth I. , Humphreys Janice C.
Published: March 2019

This integrated literature review, framed by the gender affirmation framework, sought to contextualize the experiences of transgender adults interfacing with health care after the release of Healthy People 2020. The constructs of the gender affirmation framework represented 4 a priori themes used to organize the findings. The 23 articles synthesized (quantitative, n = 13; qualitative, n = 7; case studies, n = 2; and mixed methods, n = 1) revealed numerous obstacles accessing health care, discrimination from health care professionals and clinicians, restricted health insurance benefits for medically necessary care, and barriers to medically necessary care, such as cross-sex hormones, as well as primary and preventative health care.
Towards a Definition of Caregiver Fatigue
Authors: Beydoun Jamal , Nasrallah Laya , Sabrah Talal , Caboral-Stevens Meriam
Published: March 2019

Using Walker and Avant's approach, a concept analysis was performed to develop a working definition of caregiver fatigue. Defining attributes of caregiver fatigue identified were “fell into role” by default, outside the norm of role expectations, excess caregiving demand, and exposure to prolonged period of caregiving. Model, related, and contrary cases were developed. Antecedent, consequences, and empirical referent of caregiver fatigue were also identified. Lastly, a working definition of caregiver fatigue was developed.
Towards a Guiding Framework for Prison Palliative Care Nursing Ethics
Authors: Hudson Helen , Wright David Kenneth
Published: March 2019

The number of people aging and dying behind bars is growing, bringing greater attention to the need for prison palliative care. While this trend has rightly led to increased scholarship, a focus on understanding the most effective way to deliver prison palliative care has overshadowed thinking about why the need itself has arisen, as well as deeper ethical thinking about how the nursing profession should respond. This article interweaves 4 strands of analysis—contextual, relational, social, and political—to produce a framework to guide ethical action in prison palliative care nursing, relevant to practice, research, policy, and education.
Double hindfoot arthrodesis technique for the treatment of severe equino-plano-valgus foot deformity in cerebral palsy: long-term results and radiological evaluation
Authors: Costici Pier Francesco , Donati Fabrizio , Russo Rosa , Verardi Caroline , Pagnotta Gaetano
Published: March 2019

The aim of this study was to evaluate the clinical and radiological results of a double arthrodesis technique for the treatment of equino-plano-valgus foot deformity in pediatric patients affected by cerebral palsy. A retrospective evaluation was performed on 175 feet surgically treated with a talonavicular and calcaneocuboid joint fusion technique. The average age at surgery was 14.7 years (range: 12–20 years). Visual analogue scale for pain score, Gross Motor Function Classification System scale, talonavicular angle, Costa–Bertani angle, and Kite’s angle on standard weight bearing radiographs were evaluated preoperatively and postoperatively. The mean clinical follow-up was 62.4 months (range: 12–112 months). The mid Gross Motor Function Classification System scale value did not show a significant improvement in any of the subgroups considered. A significant improvement in the visual analogue scale for pain score value was evident 6 months after surgery. Radiological examination showed a statistically significant improvement in the talonavicular angle (average 7.4°) and the Costa–Bertani angle (average 128.5°). Complications occurred in 8.6% of cases. The described surgical technique is safe and efficacious, and could represent a useful option of treatment of equino-plano-valgus severe deformity in cerebral palsy patients older than 12 years of age.
Insights Into a “Negative” ICU Trial Derived From Gene Expression Profiling
Authors: Hoekstra Mary , Maslove David M. , Veldhoen Richard A. , Marshall John C. , Muscedere John
Published: March 2019

Objectives:

Randomized controlled trials in the ICU often fail to show differences in endpoints between groups. We sought to explore reasons for this at a molecular level by analyzing transcriptomic data from a recent negative trial. Our objectives were to determine if randomization successfully balanced transcriptomic features between groups, to assess transcriptomic heterogeneity among the study subjects included, and to determine if the study drug had any effect at the gene expression level.

Design:

Bioinformatics analysis of transcriptomic and clinical data collected in the course of a randomized controlled trial.

Setting:

Tertiary academic mixed medical-surgical ICU.

Patients:

Adult, critically ill patients expected to require invasive mechanical ventilation more than 48 hours.

Interventions:

Lactoferrin or placebo delivered enterally and via an oral swab for up to 28 days.

Measurements and Main Results:

We found no major imbalances in transcriptomic features between groups. Unsupervised analysis did not reveal distinct clusters among patients at the time of enrollment. There were marked differences in gene expression between early and later time points. Patients in the lactoferrin group showed changes in the expression of genes associated with immune pathways known to be associated with lactoferrin.

Conclusions:

In this clinical trial, transcriptomic data provided a useful complement to clinical data, suggesting that the reasons for the negative result were less likely related to the biological efficacy of the study drug, and may instead have been related to poor sensitivity of the clinical outcomes. In larger studies, transcriptomics may also prove useful in predicting response to treatment.
Observational Study Examining the Diagnostic Practice of Ki67 Staining for Melanocytic Lesions
Authors: Vyas Nikki S. , Charifa Ahmad , Desman Garrett T. , Goldberg Matthew , Singh Rajendra , Phelps Robert G. , McNiff Jennifer M.
Published: March 2019

Background:

Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation.

Methods:

We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions.

Results:

Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%–90.9% sensitive and 40%–56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review.

Conclusions:

A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains.
Roles of Endothelin B Receptors and Endothelial Nitric Oxide Synthase in the Regulation of Pulmonary Hemodynamic in Cirrhotic Rats
Authors: Khoramzadeh Maryam , Dehghanian Amirreza , Ketabchi Farzaneh
Published: March 2019

Introduction:

Hepatopulmonary syndrome and portopulmonary hypertension are common complications of liver disorders. This study aimed to determine roles of ET-B receptors and endothelial-derived NO synthase in the regulation of pulmonary hemodynamic in cirrhotic rats.

Methods:

Male Sprague–Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 28 days, animals were anesthetized, and the right ventricle, femoral artery, and vein cannulated. Then, intravenous injection of BQ-788 (a selective ET-B receptor antagonist) and L-NAME (eNOS inhibitor) were performed sequentially.

Results:

After the first injection of BQ-788, the right ventricular systolic pressure (RVSP) and mean arterial systemic pressure increased only in the Sham group. L-NAME increased RVSP in the Sham and CBDL groups, whereas mean arterial systemic pressure elevated only in the Sham group significantly. Reinjection of BQ-788 increased RVSP in the Sham group, whereas it decreased RVSP in the CBDL group. Both plasma NO metabolites and lung endothelin-1 increased in the CBDL group.

Conclusion:

ET-B receptors on the endothelial cells play roles in the regulation of pulmonary and systemic vascular tone in normal condition through the NO-mediated pathway, whereas ET-B receptors on the smooth muscle cells have a role in the pulmonary vascular tone in liver cirrhosis.
Contrasting Effects of Inhibition of Phosphodiesterase 3 and 5 on Cardiac Function and Interstitial Fibrosis in Rats With Isoproterenol-Induced Cardiac Dysfunction
Authors: Nakata Telma Mary , Suzuki Kazuhiko , Uemura Akiko , Shimada Kazumi , Tanaka Ryou
Published: March 2019

Myocardial relaxation and stiffness are influenced by fibrillar collagen content. Cyclic nucleotide signaling regulators have been investigated targeting more effective modulation of collagen deposition during myocardial healing process. To assess the effects of phosphodiesterase type 3 and phosphodiesterase type 5 inhibitors on cardiac function and left ventricular myocardial fibrosis in catecholamine-induced myocardial injury, sildenafil and pimobendan were administered to male Wistar rats 24 hours after isoproterenol injection. Echocardiography and electrocardiogram were performed to assess kinetic and rhythm changes during 45 days of drug administration. At the end of study, type I and type III collagen were measured through immunohistochemistry analysis, and left ventricular pressure was assessed through invasive method. Echocardiography assessment showed increased relative wall thickness at 45 days in pimobendan group with significant diastolic dysfunction and increased collagen I deposition compared with nontreated positive group (3.03 ± 0.31 vs. 2.73 ± 0.28%, P < 0.05). Diastolic pressure correlated positively with type I collagen (r = 0.54, P < 0.05). Type III collagen analysis did not demonstrate difference among the groups. Sildenafil administration attenuated type I collagen deposition (2.15 ± 0.51 vs. positive group, P < 0.05) and suggested to be related to arrhythmic events. Arrhythmic events were not related to the quantity of fibrillar collagen deposition. Although negative modulation of collagen synthesis through cyclic nucleotides signaling have shown promising results, in this study, pimobendan postconditioning resulted in increased collagen type I formation and severe diastolic dysfunction while sildenafil postconditioning reduced collagen type I deposition and attenuated diastolic dysfunction.
Sources of Variability and Accuracy of Performance Assessment in the Clinical Pharmacology Quality Assurance Proficiency Testing Program for Antiretrovirals
Authors: Browne Richard W. , Rosenkranz Susan L. , Wang Yan , Taylor Charlene R. , DiFrancesco Robin , Morse Gene D.
Published: March 2019

Background:

The Clinical Pharmacology Quality Assurance (CPQA) program provides semiannual proficiency testing (PT) of antiretroviral analytes for 11 US and international clinical pharmacology laboratories (CPLs) to ensure interlaboratory comparability. In this article, we provide estimates of the main sources of variability and assess the accuracy of the algorithm for the assessment of performance.

Methods:

Descriptive statistics are reported from 13 PT rounds from 2010 to 2016. Eight of the most common antiretroviral analytes were examined. Variance components analysis was used to rank the relative contributions of CPLs, antiretroviral analyte, and concentration category (low, medium, and high) to bias and variability using mixed models. Binary classification metrics of the PT assessment algorithm are calculated in comparison with a model using 95% prediction limits around estimated regression equations.

Results:

CPLs provided 4109 reported concentrations of 65 unique samples for each of the 8 antiretroviral analytes across 13 PT rounds. Individual CPL accounted for the greatest amount of total variability (4.4%). Individual CPL and analyte combination (interaction) accounted for the greatest amount of bias (8.1%). Analyte alone accounted for 0.5% or less for total variability and bias. Overall, using a ±20% acceptance window around the final target, 97% of individual reported concentrations were scored acceptable, and 96% of antiretroviral/round scores were deemed satisfactory. Comparison with the regression model gave 100% sensitivity but only 34.47% specificity. Narrowing the acceptance window to ±15% improved specificity to 84.47% while maintaining a 99.17% sensitivity.

Conclusions:

The current CPQA PT scoring algorithm that use a ±20% acceptance window seems to suffer from a low specificity and may be too lenient. A stricter ±15% acceptance window would increase specificity and overall accuracy while lowering the overall pass rate by only 3%.
Menopause symptoms and chronic pain in a national sample of midlife women veterans
Authors: Gibson Carolyn J. , Li Yongmei , Bertenthal Daniel , Huang Alison J. , Seal Karen H.
Published: March 2019

Objective:

Women are more likely than men to suffer chronic pain, with the highest rates seen in midlife. The symptoms that characterize menopause broadly affect health and well-being, but their contribution to chronic pain risk during this period is poorly understood. To address this gap in knowledge, we examined relationships between indicators of menopause symptoms and chronic pain among midlife women veterans, a population with prevalent chronic pain diagnoses and elevated risk for bothersome menopause symptoms.

Methods:

This is a cross-sectional analysis of national Veterans Health Administration medical and pharmacy records. Using national medical and pharmacy records from women veterans aged 45 to 64 with at least one VA encounter during 2014 and/or 2015 (n = 200,901), we developed multivariable logistic regression models to examine associations between menopause symptoms (defined by menopause symptom-related diagnoses on ≥2 encounters and/or menopause hormone therapy use) and chronic pain outcomes, adjusting for age, race, body mass index, mental health diagnoses, and substance use disorders.

Results:

In this national sample of midlife women veterans (mean age 54.3 ± 5.4), 13% had menopause symptoms, 52% had chronic pain, and 22% had ≥2 distinct chronic pain diagnoses. In multivariable analyses, women with menopause symptoms had nearly two-fold odds of chronic pain (odds ratio 1.84, 95% confidence interval 1.79-1.90, P < 0.001) and multiple chronic pain diagnoses (odds ratio 1.79, 95% confidence interval 1.74-1.83, P < 0.001).

Conclusions:

These findings raise the possibility within this vulnerable critical period, midlife women with a higher menopause symptom burden may be most vulnerable for chronic pain.
LATE-ONSET LYSOSOMAL STORAGE DISORDER WITH MACULAR CHERRY-RED SPOT
Authors: Gahramanova Leyla , Galbinur Tural , Mammadkhanova Ayan
Published: March 2019

Background:

To report a case of late-onset lysosomal storage disorder presenting with bilateral macular cherry-red spot.

Methods:

Case report.

Results:

A 20-year-old female patient with bilateral progressive visual loss was found to have bilateral macular cherry-red spots and was subsequently diagnosed as a possible late-onset Tay–Sachs disease according to results of the genetic analysis.

Conclusion:

Most lysosomal storage disorders are known as pediatric diseases. However, we must consider the possibility of late-onset lysosomal disorder in case of progressive visual loss and macular cherry-red spot in adult patients.
Phase 2, Randomized, Dose-finding Studies of Omidenepag Isopropyl, a Selective EP2 Agonist, in Patients With Primary Open-angle Glaucoma or Ocular Hypertension
Authors: Aihara Makoto , Lu Fenghe , Kawata Hisashi , Iwata Akihiro , Liu Kathy , Odani-Kawabata Noriko , Shams Naveed K.
Published: March 2019

Précis:

Three randomized, multicenter studies demonstrated the stable intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in patients with primary open-angle glaucoma and ocular hypertension; 0.002% was identified as the optimal dose for further investigation.

Purpose:

The purpose of this study was to assess the safety and efficacy of omidenepag isopropyl, a selective EP2 agonist, and to determine the optimal dose for further investigation.

Patients and Methods:

Three randomized, controlled, masked, multicenter studies were conducted in United States (study 1, NCT01868126; study 2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the observed mean diurnal intraocular pressure (IOP) and IOP at each time point on the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at week 4 (study 3).

Results:

IOP-lowering effects of omidenepag isopropyl 0.0003% to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% resulted in clinically relevant mean diurnal IOP reductions from baseline that were similar to those of latanoprost and superior to placebo (P<0.005). Maximum reductions had already been achieved by week 1, and stable IOP-lowering effects were observed at all postbaseline time points up to 3 months. Most adverse events (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the incidence of which increased dose-dependently. The safety profiles of omidenepag isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs in the 0.002% group.

Conclusions:

Omidenepag isopropyl demonstrated stable IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal dose for phase 3 investigation.
Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma
Authors: Lin Michael M. , Rageh Abdulrahman , Turalba Angela V. , Lee Hang , Falkenstein Iryna A. , Hoguet Ambika S. , Ojha Pallavi , Rao Veena S. , Ratanawongphaibul Kitiya , Rhee Douglas J. , Shen Lucy Q. , Song Brian J. , Chen Teresa C.
Published: March 2019

Précis:

This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma.

Purpose:

Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease IOP by reducing aqueous production. Anecdotal experience in angle-closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma.

Patients and Methods:

A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted.

Results:

In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle-closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open-angle glaucoma at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14).

Conclusions:

Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.
The role of afferent input in postamputation pain: a randomized, double-blind, placebo-controlled crossover study
Authors: Buch Nina Stockfleth , Ahlburg Peter , Haroutounian Simon , Andersen Niels Trolle , Finnerup Nanna Brix , Nikolajsen Lone
Published: March 2019

In this randomized, double-blind, placebo-controlled crossover study, we investigated whether a peripheral nerve block could temporarily eliminate phantom and stump pain after amputation. Amputees with constant postamputation pain were included and randomized to receive a nerve block with lidocaine 2% with adrenaline or saline in a crossover design. Spontaneous phantom and stump pain and evoked responses were assessed at baseline and at fixed time-points until 120 minutes after lidocaine or saline injection. The primary outcome was the difference in absolute change between worst pain intensity, either phantom or stump pain, at baseline and at 30 minutes after lidocaine or saline injection. Twelve amputees were randomized and 9 patients were included in the analysis. The absolute change in median worst pain intensity between lidocaine and saline injection was −2.0 (interquartile range, −4.0 to 0.0) (n = 9, P = 0.12). Nine of 9 patients reported at least some pain relief after lidocaine injection compared with only 2 of 9 patients after saline injection (P = 0.02). Phantom pain intensity was significantly reduced after lidocaine compared with saline injection (P = 0.04), whereas there was no significant change in stump pain intensity between the 2 interventions (P = 0.17). In all 9 amputees, evoked responses were eliminated after lidocaine injection. Thus, our findings suggest that afferent input from the peripheral nervous system plays an important role in postamputation pain.
Time for change: an experimental investigation of chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice
Authors: Ashton-James Claire E. , Chemke-Dreyfus Axel , Costa Daniel , Glare Paul
Published: March 2019

Clinicians report reluctance to deliver opioid-tapering advice to patients with chronic pain, in part due to concerns that patients will be angry and dissatisfied. An experiment was conducted to examine chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice. Patients scheduled for an initial assessment at a tertiary pain clinic and currently taking opioid medications for pain (N = 196) were randomly assigned to view video footage of a standardized patient receiving 1 of 3 forms of treatment advice: (1) stay on current medication (2) change to a different pain medication, or (3) taper off pain medications and participate in a CBT-based pain self-management program. Participants reported how positive/enthusiastic, anxious/worried, and angry/irritable they felt in response to the simulated treatment advice, and how satisfied with and willing they would be to accept and follow the advice. Participants expressed more positive emotional and attitudinal responses to simulated opioid-tapering advice than to simulated opioid-maintenance advice. Furthermore, participants' responses to simulated opioid-tapering and opioid-change advice were not significantly different, suggesting that participants responded positively to the prospect of change in treatment strategy. Additional analyses revealed that participants with a longer history of chronic pain and opioid use responded less positively to simulated opioid-tapering advice. The results of this study contribute to our understanding of factors that may shape chronic pain patients' responses to opioid-tapering advice and suggest that patients may respond more positively to opioid-tapering advice if it is presented together with an alternative treatment approach.
Can a brief psychological expectancy intervention improve postoperative pain? A randomized, controlled trial in patients with breast cancer
Authors: Benson Sven , Hagen Susanne , Hoffmann Oliver , Pasler Annika , Bingel Ulrike , Schedlowski Manfred , Peters Jürgen , Elsenbruch Sigrid , Frey Ulrich H.
Published: March 2019

Pain after surgery remains a major health problem, calling for optimized treatment regimens to maximize the efficacy of pharmacological interventions. In this randomized controlled trial, we tested in a routine surgical treatment setting whether postoperative pain can be reduced by a brief preoperative intervention, ie, positive verbal suggestions in combination with sham acupuncture, designed to optimize treatment expectations. We hypothesized that the expectancy intervention as add-on to patient-controlled intravenous analgesia with morphine reduces patient-reported postoperative pain and improves satisfaction with analgesia. Ninety-six women undergoing breast cancer surgery were randomized at 2 stages: Before surgery, anesthesiologists delivered either positive or neutral verbal suggestions regarding the benefits of acupuncture needling on postoperative pain (“information condition”). Patients were then randomized to receive sham acupuncture or no sham acupuncture during postoperative care (“sham acupuncture condition”). Average pain during the 24-hour observation period after surgery as primary and satisfaction with analgesia as secondary outcome was assessed with standardized measures and analyzed with analysis of covariance accounting for morphine dose, surgery-related, and psychological parameters. Postoperative pain ratings were significantly reduced in patients who received positive treatment-related suggestions (F = 4.45, P = 0.038, main effect of information). Moreover, patients who received an intervention aimed at optimized treatment expectations reported significantly greater satisfaction with analgesia (F = 4.89, P = 0.030, interaction effect). Together, our proof-of-concept data support that optimizing treatment expectations through verbal suggestions may offer a promising approach to improve patient-reported outcomes. Future translational and clinical studies are needed to test such psychological strategies in different surgical interventions, patient groups, and pharmacological treatment regimens.
Reducing Cancellations and Optimizing Surgical Scheduling of Ophthalmology Cases at a Veterans Affairs Medical Center
Authors: Dawson Valerie J. , Margo Jordan , Blanco Natalia , Munir Wuqaas M.
Published: March 2019

Preventable causes of ophthalmology surgical case cancellations were identified, and interventions were implemented to improve operating room utilization at our Veterans Affairs (VA) Medical Center. A retrospective review of 269 patients with cancellations from 2013 to 2015 was performed. Interventions implemented from September 2014 to March 2015 were evaluated followed by in-depth chart reviews to identify demographics and wait-time intervals. Interventions included scheduling surgeries electronically, by specialty, and with predetermined attending coverage. In addition, the preoperative templates and technology to obtain preoperative measurements were updated. Cancellation rates dropped significantly from 35% to 7% (p = .014). Preventable causes of cancellations decreased from 28% to 5% (p = .005). Operating room utilization increased significantly with 264 more scheduled cases in 2015 than in 2013 (485 vs. 749, p < .001), and surgery wait time trended downward. These findings may support the use of similar interventions at other VA medical centers or similar hospitals with the goal of improving quality of care through decreased cancellations and cost.
Parents: Wish I had done, wish I had not done, and coping after child NICU/PICU death
Authors: Brooten Dorothy , Youngblut JoAnne M. , Caicedo Carmen , Dankanich Julia
Published: March 2019

Background and purpose:

An infant or child death is devastating for parents. This study examined parents' wishes regarding what they had or had not done and how they coped 1–13 months and 2–6 years after the infant's/child's neonatal intensive care unit (NICU)/pediatric intensive care unit (PICU) death.

Methods:

Qualitative study design using conventional content analysis. Eighty-one mothers and 23 fathers completed open-ended questions regarding what they wished they had or had not done and their coping strategies. Mothers wished most to have spent more time with the child (17%), held the child more (11%), and chosen a different treatment path (9%). Fathers wished most to have spent more time with the child (53%) and monitored the child more closely (12%). Mothers wished they had not taken poor care of themselves (27%) and agreed to the child's surgery/treatment (20%). Fathers wished they had not left the hospital (22%) and agreed to surgery/treatment (16%). Mothers most used coping that included caring for herself (23%) and remembering the child (17%), whereas fathers were caring for self (26%) and moving forward (20%).

Conclusions:

Parents wished they had spent more time with their child and had not agreed to the child's surgery/treatments. The most frequent coping technique used by parents was caring for themselves.

Implications for practice:

Practitioners must provide parents time with their infant/child in the NICU/PICU before and after death and provide information on children's treatments at levels and in languages they understand.
A 2-year retrospective study of viral and host-associated risk factors in Pakistani hepatocellular carcinoma patients
Authors: Ul Abideen Zain , Siddique Shafiqa , Nasrullah Izza , Khan Jahangir S. , Rehman Sidra , Tong Yigang , Qamar Raheel , Butt Azeem M.
Published: March 2019

Objective

Persistent chronic hepatitis C (CHC) infection is associated strongly with serious complications such as hepatitis C virus-associated liver cirrhosis (HCV-LC) and hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). The aim of this study was to assess the distribution of hepatitis C virus (HCV) genotypes among HCV-positive patients and examine the potential associations between viral and host-associated factors with the risk of developing HCV-HCC.

Patients and methods

HCV-positive patients (n = 300) were enrolled and divided into three groups: CHC (n = 171), HCV-LC (n = 51), and HCV-HCC (n = 78).

Results

HCV genotype 3a showed the highest prevalence among HCV-positive individuals (66% of patients), followed by genotype 1a (15% of patients). The proportion of individuals infected with mixed HCV genotypes was higher among HCV-HCC patients. Interestingly, there were a significantly higher proportion of women (54/78; 69.2%) among HCV-HCC patients compared with CHC patients (89/171 or 52%; χ
2 = 6.47; P=1 × 10−2). Women with HCV had two-fold higher odds of developing HCV-HCC (odds ratio = 2.07, 95% confidence interval: 1.18–3.71). In comparison with CHC patients, significantly more HCV-HCC patients were 50 years of age or older (59/78 or 75.6% of HCV-HCC patients and 61/171 or 35.7% of CHC patients; χ
2 = 34.27; P < 0.0001), suggesting that HCV-positive patients aged 50 years or older had an ~five-fold higher risk of developing HCV-HCC (odds ratio = 5.6, 95% confidence interval: 3.02–10.01).

Conclusion

In summary, HCV genotype 3a had the highest prevalence in the studied HCV-positive population, and women and older patients were at a higher risk of developing HCV-LC and HCV-HCC following CHC infections.
Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients
Authors: Darweesh Samar K. , AbdElAziz Rasha A. , Abd-ElFatah Dina S. , AbdElazim Naglaa A. , Fathi Shaimaa A. , Attia Dina , AbdAllah Mohammed
Published: March 2019

Background

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients.

Aim

The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients.

Patients and methods

Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group.

Results

Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001).

Conclusion

Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.
Clostridium difficile infection in inflammatory bowel disease: epidemiology over two decades
Authors: Moens Annick , Verstockt Bram , Machiels Kathleen , Bossuyt Peter , Verdonck Ann , Lagrou Katrien , van Assche Gert , Vermeire Séverine , Ferrante Marc
Published: March 2019

Background

The incidence of Clostridium difficile infection (CDI) has been rising in the overall population as well as in patients with inflammatory bowel disease (IBD). However, the incidence of CDI in IBD may be changing owing to alterations in medical therapies.

Objective

The aim of this study was to establish the incidence of CDI in IBD over the past two decades and compare risk factors, disease characteristics and outcomes between IBD and non-IBD patients.

Patients and methods

In this retrospective case–control study, the incidence of CDI in IBD was followed for 18 years. The electronic database of our centre was reviewed for all stool samples received from patients admitted to gastroenterology wards or visiting the outpatient clinic. Diagnosis of CDI was based on diagnostic criteria that evolved throughout the years.

Results

IBD patients (n=44) with CDI were found to be younger (P=0.0001), have less cardiovascular comorbidity (P=0.023), fewer prior hospitalizations (P=0.009) and fewer prior antibiotic use (P=0.005). More IBD patients were on biologic therapy (P=0.0001) or steroids (P=0.001) but less likely taking proton pump inhibitors (P=0.001). The number of stool testing per year increased as well as the median number of positive stool samples for CDI (2% in 2000–2008 to 3% in 2009–2017, P=0.032). Pseudomembranes were only seen in non-IBD patients (28%, P=0.048). There was no difference in the choice of antibiotics between IBD and non-IBD patients [metronidazole (36 vs. 51%) and vancomycin (36 vs. 26%), P=0.090 and 0.190]. The 1-year mortality rate was lower in IBD patients compared with non-IBD patients (0 vs. 32%, P=0.0001).

Conclusion

In the past two decades, the incidence of CDI in IBD and non-IBD patients has increased. However, the overall outcome of CDI in IBD patients was favourable compared with non-IBD patients.
Anticoagulation in Acute Coronary Syndrome: Review of Major Therapeutic Advances
Authors: Pop Calin , Matei Claudia , Petris Antoniu
Published: March 2019

Background:

In patients with acute coronary syndrome (ACS), a persistent hypercoagulable state has been demonstrated and antithrombin therapy in addition to platelet inhibition has been proposed.

Areas of Uncertainty:

Vitamin K antagonists (VKAs) were used as oral anticoagulant (OAC) therapy and produced mixed results whereas trials are still ongoing with non-vitamin K OACs (NOACs).

Data Sources:

A literature search regarding benefits and risks of different OAC therapies in ACS was conducted through MEDLINE and EMBASE (last 20 years until September 2018).

Therapeutic Advances:

Patients receiving dual antiplatelet therapy (DAPT) in combination with NOAC are to be considered at high bleeding risk. Rivaroxaban 2.5 mg BID in triple therapy with DAPT, rivaroxaban 15 mg, or dabigatran 110/150 mg BID in dual therapy with P2Y12 inhibitor (mainly clopidogrel) is safer in terms of bleeding risk than triple therapy with VKA plus DAPT. The reduction in ischemic events by NOACs was most promising when added to single antiplatelet therapy. Ongoing trials with apixaban and edoxaban could clarify whether dual therapy NOACs with P2Y12 inhibitor sufficiently protect against stent thrombosis or myocardial infarction and are safer in terms of bleeding risk than a dual therapy with a VKA and clopidogrel. In the absence of randomized trials, it is unknown whether dual therapy with NOAC and aspirin could be an alternative to NOAC and a P2Y12 inhibitor. Thus, the overall benefit of adding NOAC to antiplatelet treatment after ACS in patients without clear indication for long-term OAC is still unknown.

Conclusions:

Different OACs have been tested as antithrombotic therapy after ACS in combination with single or DAPT and led to a modest reduction in ischemic events. Further studies evaluating NOACs in combination with single antiplatelet therapy or shorter duration of triple antithrombotic therapy are warranted.