bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of pulmonary nodules in decision-making and management of patients diagnosed with esophageal cancer
Authors: Dellaportas D , Laliotis A , Zylstra J , Davies A , Gossage J A ,   Guy’s & St Thomas’ Oesophago-Gastric Research Group
Published: October 2019

In esophageal cancer, metastatic spread to the lungs is detected in 4–9.7% of cases. During staging investigations, 22% of patients have pulmonary nodules detected on cross-sectional imaging. The purpose of this study is to elucidate the clinical importance of these incidentally found pulmonary nodules, in patients with clinically localized esophageal cancer. A retrospective cohort study was conducted from January 2008 to December 2012 in a tertiary esophagogastric referral center. One-hundred and forty-nine patients were included in the study. All patients underwent dedicated staging followed by neoadjuvant chemotherapy and surgery as indicated. Thirty-three (22.1%) patients had pulmonary nodules found in their preoperative staging. Only three (9%) patients proved to develop metastatic pulmonary disease on follow-up. Interestingly, in all three patients, the nodules were negative on initial 18−fluorodeoxyglucose positron emission tomography.

Incidentally found pulmonary nodules in newly diagnosed patients with esophageal cancer during staging investigations are rarely metastases. Such nodules, in isolation, should not preclude patients from radical treatment.
Delayed prescribing of antibiotics for acute respiratory infections by GP registrars: a qualitative study
Authors: Dallas Anthea , Davey Andrew , Mulquiney Katie , Davis Joshua , Glasziou Paul , Van Driel Mieke , Magin Parker
Published: October 2019

Background

Antibiotic prescribing for acute self-limiting respiratory tract infections (ARTIs) in Australia is higher than international benchmarks. Antibiotics have little or no efficacy in these conditions, and unnecessary use contributes to antibiotic resistance. Delayed prescribing has been shown to reduce antibiotic use. GP registrars are at a career-stage when long-term prescribing patterns are being established.

Aim

To explore experiences, perceptions and attitudes of GP registrars and supervisors to delayed antibiotic prescribing for ARTIs.

Design and setting

A qualitative study of Australian GP registrars and supervisors using a thematic analysis approach.

Method

GP registrars and supervisors were recruited across three Australian states/territories, using maximum variation sampling. Telephone interviews explored participants’ experience and perceptions of delayed prescribing of antibiotics in ARTIs. Data collection and analysis were concurrent and iterative.

Results

A total of 12 registrars and 10 supervisors were interviewed. Key themes included the use of delayed prescribing as a safety-net in cases of diagnostic uncertainty or when clinical review was logistically difficult. Delayed prescribing was viewed as a method of educating and empowering patients, and building trust and the doctor–patient relationship. Conversely, it was also seen as a loss of control over management decisions. Supervisors, more so than registrars, appreciated the psychosocial complexity of ARTI consultations and the importance of delayed antibiotic prescribing in this context.

Conclusion

Better awareness and understanding by GP registrars of the evidence for delayed antibiotic prescription may be a means of reducing antibiotic prescribing. Understanding both registrar and supervisor usage, uncertainties and attitudes should inform educational approaches on this topic.
Gene Composition as a Potential Barrier to Large Recombinations in the Bacterial Pathogen Klebsiella pneumoniae
Authors: Comandatore Francesco , Sassera Davide , Bayliss Sion C , Scaltriti Erika , Gaiarsa Stefano , Cao Xiaoli , Gales Ana C , Saito Ryoichi , Pongolini Stefano , Brisse Sylvain , Feil Edward J , Bandi Claudio
Published: October 2019

Klebsiella pneumoniae (Kp) is one of the most important nosocomial pathogens worldwide, able to cause multiorgan infections and hospital outbreaks. One of the most widely disseminated lineage of Kp is the clonal group 258 (CG258), which includes the highly resistant “high-risk” sequence types ST258 and ST11. Genomic investigations revealed that very large recombination events have occurred during the emergence of Kp lineages. A striking example is provided by ST258, which has undergone a recombination event that replaced over 1 Mb of the genome with DNA from an unrelated Kp donor. Although several examples of this phenomenon have been documented in Kp and other bacterial species, the significance of these very large recombination events for the emergence of either hypervirulent or resistant clones remains unclear. Here, we present an analysis of 834 Kp genomes that provides data on the frequency of these very large recombination events (defined as those involving >100 kb), their distribution within the genome, and the dynamics of gene flow within the Kp population. We note that very large recombination events occur frequently, and in multiple lineages, and that the majority of recombinational exchanges are clustered within two overlapping genomic regions, which have been involved by recombination events with different frequencies. Our results also indicate that certain lineages are more likely to act as donors to CG258. Furthermore, comparison of gene content in CG258 and non-CG258 strains agrees with this pattern, suggesting that the success of a large recombination depends on gene composition in the exchanged genomic portion.
Asymptotically conical Calabi-Yau metrics with cone singularities along a compact divisor
Authors: de Borbon Martin , Spotti Cristiano
Published: October 2019

We construct Asymptotically Locally Euclidean (ALE) and, more generally, asymptotically conical Calabi–Yau metrics with cone singularities along a compact simple normal crossing divisor. In particular, this includes the case of the minimal resolution of 2D quotient singularities for any finite subgroup $\Gamma \subset U(2)$ acting freely on the three-sphere, hence generalizing Kronheimer’s construction of smooth ALE gravitational instantons.
Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen
Authors: Endy Timothy P , Keiser Paul B , Cibula Don , Abbott Mark , Ware Lisa , Thomas Stephen J , Polhemus Mark E
Published: October 2019

Background

Chloroquine can impair the immune responses to intradermal rabies vaccination. Current guidelines recommend an extra intramuscular dose be given for postexposure prophylaxis in previously unvaccinated persons taking any antimalarial drug.

Methods

We conducted a randomized, open-label, single-site study in 103 previously unvaccinated healthy adults age ≥18 to ≤60 years old to evaluate the effects of chloroquine, atovaquone/proguanil (Malarone), and doxycycline on the antibody response to a purified chick embryo cell vaccine, given on a postexposure prophylaxis schedule. All treatment groups received antimalarials 14 days prior to and during vaccination.

Results

All subjects achieved accepted neutralizing antibody titers of ≥0.5 IU/mL following the second rabies vaccination dose and maintained this protection through the duration of the study. We observed a reduction in rabies antibody geometric mean titer in the chloroquine versus control groups 28 days after vaccination: 2.3 versus 6.87 IU/mL, respectively (P < .001, t test). A significant difference was not observed for those taking Malarone or doxycycline.

Conclusions

We conclude that there is no reduction of rabies antibody response in subjects taking Malarone or doxycycline, but a significant reduction in those taking chloroquine; however, accepted antibody levels were achieved for all 3 antimalarials.

Clinical Trials Registration

NCT02564471.
Characterizing the impact of health literacy, computer ability, patient demographics, and portal usage on patient satisfaction with a patient portal
Authors: Wong Joseph Isaac Salientes , Steitz Bryan D , Rosenbloom Samuel Trent
Published: October 2019

Objective

We sought to measure patient portal satisfaction with patient portals and characterize its relationship to attitude towards computers, health literacy, portal usage, and patient demographics.

Materials and Methods

We invited 13 040 patients from an academic medical center to complete a survey measuring satisfaction, perceived control over computers, and health literacy using validated instruments (End User Computing Satisfaction, Computer Attitude Measure, and Brief Health Literacy Screen). We extracted portal usage and demographic information from the medical center data warehouse.

Results

A total of 6026 (46.2%) patients completed the survey. The median (IQR) scores for satisfaction, computer control, and health literacy were 87% (20%), 86% (22%), and 95% (15%), respectively. The normalized mean (SD) usage of messaging, lab, appointment, medication, and immunization functions were 6.6 (2.6), 4.6 (2.4), 3.1 (1.7), 1.5 (1.2), and 0.88 (0.91) times, respectively. Logistic regression yielded significant odds ratios [99% CI] for computer control (3.6 [2.5–5.2]), health literacy (12 [6.9–23]), and immunization function usage (0.84 [0.73–0.96]).

Discussion

Respondents were highly satisfied and had high degrees of computer control and health literacy. Statistical analysis revealed that higher computer control and health literacy predicted higher satisfaction, whereas usage of the immunization function predicted lower satisfaction. Overall, the analytical model had low predictive capability, suggesting that we failed to capture the main drivers of satisfaction, or there was inadequate variation in satisfaction to delineate its contributing factors.

Conclusion

This study provides insight into patient satisfaction with and usage of a patient portal. These data can guide the development of the patient portal, with the ultimate goal of increasing functionality and usability to enhance the patient experience.
Alice Stopford Green and Vernon Lee: Salon Culture and Intellectual Exchange
Authors: Ní Bheacháin Caoilfhionn , Mitchell Angus
Published: October 2019

Archival evidence of the connection between Alice Stopford Green (1847–1929) and Vernon Lee (1856–1935) is restricted to a handful of letters and a few scattered references in ancillary documents. Extant correspondence provides a glimpse into the conversation and concerns of these two important European intellectuals, demonstrating their nascent interest in questions of social justice. Using network theory as a lens, this essay traces the contours of this connection, initiated during a formative period for both in the fertile context of the salons and dining rooms of London in the 1880s. This connection demonstrates the importance of social networks for women writers, artists, intellectuals and activists during the fin de siècle. By exploring the limited archival remnants of this friendship, this study highlights the Irish and European dimensions of Victorian metropolitan culture. It was because of salon culture that women with strikingly different backgrounds and sensibilities could connect and explore ideas of mutual concern, with reverberations for their political positioning and activism in subsequent decades.
Radiative pulsar magnetospheres: aligned rotator
Authors: Pétri J
Published: October 2019

Force-free neutron star magnetospheres are nowadays well known and found through numerical simulations. Even extension to general relativity has recently been achieved. However, those solutions are by definition dissipationless, meaning that the star is unable to accelerate particles and let them radiate any photon. Interestingly, the force-free model has no free parameter however it must be superseded by a dissipative mechanism within the plasma. In this Letter, we investigate the magnetosphere electrodynamics for particles moving in the radiation reaction regime, using the limit where acceleration is fully balanced by radiation, also called Aristotelian dynamics. An Ohm’s law is derived, from which the dissipation rate is controlled by a one parameter family of solutions depending on the pair multiplicity κ. The spatial extension of the dissipation zone is found self-consistently from the simulations. We show that the radiative magnetosphere of an aligned rotator tends to the force-free regime whenever the pair multiplicity becomes moderately large, κ ≫ 1. However, for low multiplicity, a substantial fraction of the spin-down energy goes into particle acceleration and radiation in addition to the Poynting flux, the latter remaining only dominant for large multiplicities. We show that the work done on the plasma occurs predominantly in the equatorial current sheet right outside the light-cylinder.
UCSC Genome Browser enters 20th year
Authors: Lee Christopher M , Barber Galt P , Casper Jonathan , Clawson Hiram , Diekhans Mark , Gonzalez Jairo Navarro , Hinrichs Angie S , Lee Brian T , Nassar Luis R , Powell Conner C , Raney Brian J , Rosenbloom Kate R , Schmelter Daniel , Speir Matthew L , Zweig Ann S , Haussler David , Haeussler Maximilian , Kuhn Robert M , Kent W James
Published: October 2019

The University of California Santa Cruz Genome Browser website (https://genome.ucsc.edu) enters its 20th year of providing high-quality genomics data visualization and genome annotations to the research community. In the past year, we have added a new option to our web BLAT tool that allows search against all genomes, a single-cell expression viewer (https://cells.ucsc.edu), a ‘lollipop’ plot display mode for high-density variation data, a RESTful API for data extraction and a custom-track backup feature. New datasets include Tabula Muris single-cell expression data, GeneHancer regulatory annotations, The Cancer Genome Atlas Pan-Cancer variants, Genome Reference Consortium Patch sequences, new ENCODE transcription factor binding site peaks and clusters, the Database of Genomic Variants Gold Standard Variants, Genomenon Mastermind variants and three new multi-species alignment tracks.
A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS
Authors: Yang Yidai , Joshi Monika , Takahashi Yoh-hei , Ning Zhibin , Qu Qianhui , Brunzelle Joseph S , Skiniotis Georgios , Figeys Daniel , Shilatifard Ali , Couture Jean-François
Published: October 2019

COMPlex ASsociating with SET1 (COMPASS) is a histone H3 Lys-4 methyltransferase that typically marks the promoter region of actively transcribed genes. COMPASS is a multi-subunit complex in which the catalytic unit, SET1, is required for H3K4 methylation. An important subunit known to regulate SET1 methyltransferase activity is the CxxC zinc finger protein 1 (Cfp1). Cfp1 binds to COMPASS and is critical to maintain high level of H3K4me3 in cells but the mechanisms underlying its stimulatory activity is poorly understood. In this study, we show that Cfp1 only modestly activates COMPASS methyltransferase activity in vitro. Binding of Cfp1 to COMPASS is in part mediated by a new type of monovalent zinc finger (ZnF). This ZnF interacts with the COMPASS’s subunits RbBP5 and disruption of this interaction blunts its methyltransferase activity in cells and in vivo. Collectively, our studies reveal that a novel form of ZnF on Cfp1 enables its integration into COMPASS and contributes to epigenetic signaling.
Acyl‐CoA synthetase 6 regulates long‐chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice
Authors: Shishikura Kyosuke , Kuroha Sayoko , Matsueda Shinnosuke , Iseki Hachiro , Matsui Takeshi , Inoue Azusa , Arita Makoto
Published: October 2019

Long‐chain polyunsaturated fatty acids (LCPUFAs), such as docosahexaenoic acid (DHA, 22:6) and docosapentaenoic acid (DPA, 22:5), have versatile physiologic functions. Studies have suggested that DHA and DPA are beneficial for maintaining sperm quality. However, their mechanisms of action are still unclear because of the poor understanding of DHA/DPA metabolism in the testis. DHA and DPA are mainly stored as LCPUFA‐containing phospholipids and support normal spermatogenesis. Long‐chain acyl‐conenzyme A (CoA) synthetase (ACSL) 6 is an enzyme that preferentially converts LCPUFA into LCPUFA‐CoA. Here, we report that ACSL6 knockout (KO) mice display severe male infertility due to attenuated sperm numbers and function. ACSL6 is highly expressed in differentiating spermatids, and ACSL6 KO mice have reduced LCPUFA‐containing phospholipids in their spermatids. Delayed sperm release and apoptosis of differentiated spermatids were observed in these mice. The results of this study indicate that ACSL6 contributes to the local accumulation of DHA‐ and DPA‐containing phospholipids in spermatids to support normal spermatogenesis.—Shishikura, K., Kuroha, S., Matsueda, S., Iseki, H., Matsui, T., Inoue, A., Arita, M. Acyl‐CoA synthetase 6 regulates long‐chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice. FASEB J. 33, 14194‐14203 (2019). www.fasebj.org
Telomere length tracking in children and their parents: implications for adult onset diseases
Authors: Benetos Athanase , Verhulst Simon , Labat Carlos , Lai Tsung‐Po , Girerd Nicolas , Toupance Simon , Zannad Faiez , Rossignol Patrick , Aviv Abraham
Published: October 2019

Adults with comparatively short or long leukocyte telomere length (LTL) typically continue to display comparatively short or long LTL throughout life. This LTL tracking stems from the inability of person‐to‐person variation in age‐dependent LTL shortening during adulthood to offset the wide interindividual LTL variation established prior to adult life. However, LTL tracking in children is unstudied. This study aimed to examine LTL shortening rates and tracking in children and their parents. Longitudinal study in children (n = 67) and their parents (n = 99), whose ages at baseline were 11.4 ± 0.3 and 43.4 ± 0.4 yr, respectively. LTL was measured by Southern blotting at baseline and ~14 yr thereafter. LTL displayed tracking in both children [intraclass correlation coefficient (ICC) = 0.905, P < 0.001] and their parents (ICC = 0.856, P < 0.001). The children's rate of LTL shortening was twice that of their parents (40.7 ± 2.5 bp/yr; 20.3 ± 2.1 bp/yr, respectively; P < 0.0001). LTL tracking applies not only to adulthood but also to the second decade of life. Coupled with previous work showing that the interindividual variation in LTL across newborns is as wide as in their parents, these findings support the thesis that the LTL‐adult disease connection is principally determined before the second decade of life, perhaps mainly at birth.—Benetos, A., Verhulst, S., Labat, C., Lai, T.‐P., Girerd, N., Toupance, S., Zannad, F., Rossignol, P., Aviv, A. Telomere length tracking in children and their parents: implications for adult onset diseases. FASEB J. 33, 14248‐14253 (2019). www.fasebj.org
Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina
Authors: Xiao Meichun , Liu Yang , Wang Lingyu , Liang Jian , Wang Tianjun , Zhai Yuanqi , Wang Yafang , Liu Shu , Liu Wenjia , Luo Xueting , Wang Fenghua , Sun Xiaodong
Published: October 2019

VEGF is a critical driver of ocular neovascularization under disease conditions. Current therapeutic strategies rely on intraocular delivery of VEGF‐antagonizing reagents, which results in sustained suppression of pathogenic vascularization. Although significant advancement has been achieved in VEGF antagonism, substantial adverse effects have been reported in retrospective clinical studies. To study mechanisms for VEGF antagonism‐associated adverse effects in visual system, we intravitreally delivered recombinant adeno‐associated virusmediated expression of soluble Fms‐related tyrosine kinase‐1 (rAAV.sFLT‐1), the extracellular domain of VEGF receptor, and analyzed the morphology and functions of retinal tissue. Here, we confirmed that intraocular VEGF antagonism induced retinal degeneration and gliosis. The functional deficit in retinal response to visual stimulation was also demonstrated in rAAV.sFLT‐1‐treated eyes by electroretinogram. Moreover, high‐throughput RNA sequencing analysis suggests that VEGF antagonism activates retinal degeneration, inflammation, and other adverse effects. Taken together, our findings have shed light on pathogenic mechanisms for VEGF antagonism‐associated adverse effects and potential therapeutic targets.—Xiao, M., Liu, Y., Wang L., Liang, J., Wang T., Zhai, Y., Wang Y., Liu S. Liu W. Luo X. Wang F. Sun X. Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina. FASEB J. 33, 13920‐13934 (2019). www.fasebj.org
CAT1/SLC7A1 acts as a cellular receptor for bovine leukemia virus infection
Authors: Bai Lanlan , Sato Hirotaka , Kubo Yoshinao , Wada Satoshi , Aida Yoko
Published: October 2019

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, the most common neoplastic disease of cattle, which is closely related to human T‐cell leukemia viruses. BLV has spread worldwide and causes a serious problem for the cattle industry. The cellular receptor specifically binds with viral envelope glycoprotein (Env), and this attachment mediates cell fusion to lead virus entry. BLV Env reportedly binds to cationic amino acid transporter 1 (CAT1)/solute carrier family 7 member 1 (SLC7A1), but whether the CAT1/SLC7A1 is an actual receptor for BLV remains unknown. Here, we showed that CAT1 functioned as an infection receptor, interacting with BLV particles. Cells expressing undetectable CAT1 levels were resistant to BLV infection but became highly susceptible upon CAT1 overexpression. CAT1 exhibited specific binding to BLV particles on the cell surface and colocalized with the Env in endomembrane compartments and membrane. Knockdown of CAT1 in permissive cells significantly reduced binding to BLV particles and BLV infection. Expression of CAT1 from various species demonstrated no species specificity for BLV infection, implicating CAT1 as a functional BLV receptor responsible for its broad host range. These findings provide insights for BLV infection and for developing new strategies for treating BLV and preventing its spread.—Bai, L., Sato, H., Kubo, Y., Wada, S., Aida, Y. CAT1/SLC7A1 acts as a cellular receptor for bovine leukemia virus infection. FASEB J. 33, 14516‐14527 (2019). www.fasebj.org
The Vaginal Microbiome as a Predictor for Outcome of In Vitro Fertilization With or Without Intracytoplasmic Sperm Injection: A Prospective Study
Authors: Koedooder R. , Singer M. , Schoenmakers S. , Savelkoul P. H. M. , Morré S. A. , de Jonge J. D. , Poort L. , Cuypers W. J. S. S. , Beckers N. G. M. , Broekmans F. J. M. , Cohlen B. J. , den Hartog J. E. , Fleischer K. , Lambalk C. B. , Smeenk J. M. J. S. , Budding A. E. , Laven J. S. E.
Published: October 2019

(Abstracted from Human Reproduction 2019;34(6):1042–1054)

Nearly one third of all subfertility causes remain unexplained. In addition, assisted-reproductive technologies (ARTs) such as IVF-ICSI are invasive and only 25% to 35% of women become pregnant after the first embryo transfer (ET).
Massachusetts’ Parental Consent Law and Procedural Timing Among Adolescents Undergoing Abortion
Authors: Janiak Elizabeth , Fulcher Isabel R. , Cottrill Alischer A. , Tantoco Nicole , Mason Ashley H. , Fortin Jennifer , Sabino Jamie , Goldberg Alisa B.
Published: October 2019

(Abstracted from Obstet Gynecol 2019;133:978–986)

Thirty-seven states mandate parental consent or notification before providing abortion care to minors. In Massachusetts' parental consent law, a minor (17 years old or younger) requires parental approval before a legal abortion is permitted, but parental involvement can be bypassed through some mechanism, such as a petition to a judge (“judicial bypass”).
Clinical Utility of Expanded Carrier Screening: Results-Guided Actionability and Outcomes
Authors: Johansen Taber Katherine A. , Beauchamp Kyle A. , Lazarin Gabriel A. , Muzzey Dale , Arjunan Aishwarya , Goldberg James D.
Published: October 2019

(Abstracted from Genet Med 2019;21(5):1041–1048)

One in 300 pregnancies is impacted by a recessive or X-linked condition. Universal screening is recommended by guidelines for 2 of these conditions (cystic fibrosis and spinal muscular atrophy), but this misses approximately 70% of carriers of other diseases and fails to detect somewhere between 13% and 94% of pregnancies affected with severe conditions, depending on race/ethnicity.
Analgesic and Respiratory Depressant Effects of R-dihydroetorphine
Authors: Olofsen Erik , Boom Merel , Sarton Elise , van Velzen Monique , Baily Paul , Smith Kevin J. , Oksche Alexander , Dahan Albert , Niesters Marieke
Published: October 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

There is an ongoing need for potent opioids with less adverse effects than commonly used opioids. R-dihydroetorphine is a full opioid receptor agonist with relatively high affinity at the μ-, δ- and κ-opioid receptors and low affinity at the nociception/orphanin FQ receptor. The authors quantified its antinociceptive and respiratory effects in healthy volunteers. The authors hypothesized that given its receptor profile, R-dihydroetorphine will exhibit an apparent plateau in respiratory depression, but not in antinociception.

Methods

The authors performed a population pharmacokinetic–pharmacodynamic study (Eudract registration No. 2009-010880-17). Four intravenous R-dihydroetorphine doses were studied: 12.5, 75, 125, and 150 ng/kg (infused more than 10 min) in 4 of 4, 6 of 6, 6 of 6, and 4 of 4 male subjects in pain and respiratory studies, respectively. The authors measured isohypercapnic ventilation, pain threshold, and tolerance responses to electrical noxious stimulation and arterial blood samples for pharmacokinetic analysis.

Results

R-dihydroetorphine displayed a dose-dependent increase in peak plasma concentrations at the end of the infusion. Concentration-effect relationships differed significantly between endpoints. R-dihydroetorphine produced respiratory depression best described by a sigmoid EMAX-model. A 50% reduction in ventilation in between baseline and minimum ventilation was observed at an R-dihydroetorphine concentration of 17 ± 4 pg/ml (median ± standard error of the estimate). The maximum reduction in ventilation observed was at 33% of baseline. In contrast, over the dose range studied, R-dihydroetorphine produced dose-dependent analgesia best described by a linear model. A 50% increase in stimulus intensity was observed at 34 ± 11 pg/ml.

Conclusions

Over the dose range studied, R-dihydroetorphine exhibited a plateau in respiratory depression, but not in analgesia. Whether these experimental advantages extrapolate to the clinical setting and whether analgesia has no plateau at higher concentrations than investigated requires further studies.
Central nervous system vasculitis: advances in diagnosis
Authors: Hajj-Ali Rula A. , Calabrese Leonard H.
Published: October 2019

Purpose of review

The main purpose of this review is to present advances in diagnostics of central nervous system vasculitis (CNS-V).

Recent findings

Progress in molecular technologies and neuroimaging have added formidably to our knowledge of CNS-V. Next-generation sequencing has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases, making this test attractive and capable of avoiding brain biopsy in cases where CNS infections are suspected. Further the continuum of neuroimaging progress has advanced our ability to diagnose CNS-V. Our capability to visualize the vessel wall have added a great value in differentiating inflammatory from noninflammatory vasculopathies. New genetic variations are being exposed with exome and genome sequences which will aid future diagnosis.

We have witnessed tremendous advances in CNS-V mainly by our ability to rule out mimics. Progress in molecular technologies, neuroimaging and genetic studies will continue to enhance the field further.
Impact of Surrounding Canal Size on Time to Union After Intramedullary Nailing of Femur Fractures: Are 10-mm Nails All We Need?
Authors: Yoon Richard S. , Adams Donald M. , Seigerman Daniel A. , Lim Philip K. , Donegan Derek J. , Liporace Frank A.
Published: October 2019

Objective:

To determine whether intramedullary nail (IMN) size and its relation to the canal diameter [nail-canal (NC) diameter] impacts the union rate or time to union in the treatment of femoral shaft fractures.

Design:

Retrospective review.

Setting:

Two Level 1 and 1 Level 2 trauma centers.

Patients:

Two hundred eighty-seven patients met the criteria and were included in the study.

Intervention:

Patients were treated with either an antegrade or retrograde IMN. Comparisons were first performed comparing 10- versus 11- versus 13-mm nails. Patients were then divided into 3 groups based on the difference between the size of the femoral canal at the isthmus and the IMN (NC diameter). Group 1: <1.0 mm, group 2: >1.0 and <2.0 mm, and group 3: >2.0 mm.

Main Outcome Measurements:

Nonunion rates, mean time to union.

Results:

Two hundred eighty-seven patients with a minimum of 12-month follow-up, who were treated with size with IMN for femoral shaft fractures, were assessed for fracture characteristics, time to union, and union rate. When comparing IMN size, no statistical difference was found when comparing time to union or overall union rate. When comparing NC diameter, no significant difference was found in union rate and time to union when comparing between the groups.

Conclusion:

Similar rate of union and time to union were exhibited regardless of nail size or NC diameter. This can correlate to the standard utilization of a reamed, titanium 10-mm IMN with 5.0-mm interlocking screws in the treatment of femoral shaft fractures, offering potentially less reaming, shorter operative times, and removing unnecessary stock from inventory.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Prostate cancer screening in Portugal: prevalence and perception of potential benefits and adverse effects
Authors: Braga Raquel , Costa Ana Rute , Pina Francisco , Moura-Ferreira Pedro , Lunet Nuno
Published: October 2019

Introduction:

Opportunistic screening for prostate cancer has been widely used, though organized programs are not recommended. We aimed to estimate the prevalence of prostate cancer screening and the perception of potential benefits and harms of screening, among the Portuguese general population.

Methods:

A representative sample of Portuguese-speaking inhabitants in mainland Portugal was selected, using a stratified probabilistic sampling procedure; men above 40 were considered for analysis (n = 414). Data on sociodemographic characteristics, lifetime use and usual frequency of prostate cancer screening (prostate-specific antigen test or digital rectal examination) and perception of potential benefits and adverse effects of cancer screening were assessed using face-to-face interviews, by structured questionnaire.

Results:

The proportion of participants who reported having been submitted to prostate cancer screening at least once in their lifetime was 44.2% (95% confidence interval: 37.5–51.0; 13.8% only digital rectal examination, 12.2% only prostate-specific antigen test, and 18.2% digital rectal examination and prostate-specific antigen test). As potential benefits of cancer screening, the options “knowledge of not having the disease”, “earlier detection” and “more effective treatment” were selected by 55.8%, 12.9% and 31.3% of the participants, respectively. Regarding potential adverse effects, the most and least frequently identified were ‘anxiety while waiting for the results’ (55.1%) and ‘false negatives’ (38.0%), respectively.

Conclusions:

Almost half of the men between 40 and 79 years old declared that they have been screened for prostate cancer. Nearly one-third of the participants considered that reassurance of a negative result was the main potential benefit of screening, whereas most failed to identify the most frequent adverse effects.
Comparing the Two Techniques for Nursing Staff Rescheduling to Streamline Nurse Managers' Daily Work in Finland
Authors: Tuominen Outi , Lundgren-Laine Heljä , Teperi Simo , Salanterä Sanna
Published: October 2019

The aim of this study was to identify nurse managers' daily tasks during the rescheduling of sudden nursing staff absences by comparing two techniques: a paper-based system as phone calls and emails or information technology–based staffing systems. In addition, it is intended to evaluate the usability of information technology–based staffing solutions and evaluate estimated cost savings by using hospital permanent staff to cover sudden absences. A quasi-experimental pretest and posttest one-group study design was used to evaluate nurse managers' (n = 61) daily tasks (n = 5800) during rescheduling nursing staff sudden absences (n = 2628); furthermore, we engaged in observations and provided estimates of cost savings generated by our proposed intervention. The number of nurse manager tasks during rescheduling decreased significantly (P < .001) as well as unstaffed shifts (P < .001) and unplanned shift changes (P < .001) after the information technology–based scheduling system was implemented. The usability score ranged from 76 to 100, showing that the information technology–based scheduling solution has good usability. The use of information technology–based staffing solution can streamline the rescheduling process, save nurse managers time for other activities, and offer organizations opportunities for cost savings.
Fentanyl overdoses and pharmacogenetics
Authors: Gerhard Glenn S. , Kaniper Scott , Paynton Barbara
Published: October 2019

Fentanyl has been implicated as a major contributor to the increased number of opioid overdose deaths. Surprisingly, little is known about the pharmacogenetic influences on fentanyl pharmacokinetics or pharmacodynamics. Pharmacogenetic studies of fentanyl are based largely on small sample sizes and have examined the potential association of only a small number of high frequency variants in selected candidate genes primarily with postoperative pain. Few data are available on low frequency variants, variants from racially/ethnically diverse populations, or on other phenotypes. Given the genetic diversity of low frequency variants, DNA sequencing may be needed to determine whether pharmacogenetic differences may contribute to lethal opioid overdoses.
Increased detection of suspected atrial fibrillation in elderly and female hypertensive patients through home blood pressure monitoring: the HOME-AF study
Authors: Savvari Paraskevi , Triantafyllidi Helen , Skiadas John , Kalogeropoulos Petros , Menegas Damianos , Manolis Athanasios , Papoulidis Neofitos , Andrikopoulos George , Tsioufis Konstantinos
Published: October 2019

Background:

Episodes of suspected atrial fibrillation are particularly frequent in essential hypertension. This study aimed to investigate the incidence of new suspected atrial fibrillation cases detected through home blood pressure (BP) screening among hypertensive patients. Association of new suspected atrial fibrillation cases with arterial hypertension (AH) phenotypes and the CHA2DS2-VASc score was also investigated.

Methods:

The prospective study recruited hypertensive patients at least 50 years old from private and hospital hypertensive clinics. An ECG was performed during the first visit. Microlife BP A6 PC was used to measure office and home BP for at least 3 and preferably 7 consecutive days.

Results:

A total of 2408 AH patients were recruited. Suspected atrial fibrillation was detected by BP monitor in 12.5% of patients. CHA2DS2-VASc was greater in hypertensive patients with suspected atrial fibrillation detection, as compared with all other hypertensive patients (3.3 ± 1.4 vs. 2.8 ± 1.4, P < 0.0001). Suspected atrial fibrillation detection was associated with advanced age (≥ 75 years, P < 0.0001) and female sex (P = 0.01). A nonsignificant association between suspected atrial fibrillation detection and history of chronic heart failure/left ventricular dysfunction was observed (P = 0.06). In the multivariate analysis, age and sex were the only independent risk factors with patients at least 75 years old having more than twice the risk of suspected atrial fibrillation compared with patients less than 64 years old. No differences between new suspected atrial fibrillation cases and AH phenotype (white coat/uncontrolled/masked hypertension) were identified.

Conclusion:

In our cohort of hypertensive patients, suspected atrial fibrillation was common particularly among elderly and female patients. These results underline the need for early suspected atrial fibrillation detection to minimize the increased thromboembolic risk associated with hypertension.
Long-term Results of Corneal Wedge Resection for High Postkeratoplasty Astigmatism
Authors: Mejía Luis F. , Gil Juan C. , Naranjo Santiago
Published: October 2019

Purpose:

To present the results of corneal wedge resection in postkeratoplasty astigmatism, performed by the same surgeon using the same nomogram over a 25-year period.

Methods:

This is a retrospective observational study. The sample was obtained from the medical records of all patients who underwent penetrating or deep lamellar keratoplasty, performed by a single surgeon from 1993 to 2018. All surgeries were performed using a diamond knife, on the flat meridian, involving the keratoplasty scar and closed with five 10-0 nylon sutures.

Results:

A total of 39 eyes were included. The keratometry measured cylinder improved from 7.99 ± 0.25 to 2.5 ± 0.3 D at 12 months and remained stable thereafter (a mean follow-up of 76.3 months). Best spectacle corrected visual acuity increased from 0.35 ± 0.01 to 0.57 ± 0.02 at 12 months and remained stable thereafter. There was a coupling ratio of 0.08 ± 0.03 D at 12 months. There were no corneal graft rejections or loss of best spectacle corrected visual acuity on this series.

Conclusions:

Corneal wedge resection is a valuable resource for the management of high postkeratoplasty astigmatism. It is a safe and reproducible procedure, with stable results at 12 months and thereafter.
The effect of inspiratory muscle training on swimming performance, inspiratory muscle strength, lung function, and perceived breathlessness in elite swimmers: a randomized controlled trial
Authors: Cunha Marisa , Mendes Francisca , Paciência Inês , Rodolfo Ana , Carneiro-Leão Leonor , Rama Tiago , Rufo João , Delgado Luís , Moreira André
Published: October 2019

Background:

According to studies performed on terrestrial sports athletes, inspiratory muscle training (IMT) may improve athletes’ performance. However, evidence of its effects in elite swimmers is lacking. Therefore, we aimed to assess the effect of 12-week IMT on swimming performance, inspiratory muscle strength, lung function, and perceived breathlessness in elite swimmers.

Methods:

Elite swimmers from the main FC Porto swimming team (in competitive training for a minimum period of 3 years) were invited to participate and were randomly allocated into intervention or control groups. The intervention group performed 30 inspiratory efforts, twice a day, 5 times a week, against a pressure threshold load equivalent to 50% of maximal inspiratory pressure, whereas the control group performed inspiratory efforts at the same frequency but against a 15% load. Swimming performance was assessed through time trials, converted into points according to International Swimming Federation Points Table. Outcomes were evaluated before and following the 12-week study period.

Results:

A total of 32 participants (22 girls) were included. The median age was 15 and 14 years old for the intervention (n = 17) and control (n = 12) groups, respectively. No differences were found in swimming performance (P = .271), inspiratory muscle strength (P = .914), forced vital capacity (P = .262), forced expiratory volume in 1st second (P = .265), peak expiratory flow (P = .270), and perceived breathlessness (P = .568) between groups after 12 weeks of intervention.

Conclusion:

Twelve weeks of IMT had no effect on swimming performance, lung function, and perceived breathlessness in elite swimmers. These results may be related to swimming-specific factors and/or an applied load insufficient to achieve training overload that could induce further improvements.
Hepatitis B virus infection and the risk of liver disease progression in type 2 diabetic patients with potential nonalcoholic fatty liver disease: a retrospective, observational, cohort study in the United Kingdom Clinical Practice Research Datalink
Authors: Ferreira Germano , Stuurman Anke L. , Horsmans Yves , Cattaert Tom , Verstraeten Thomas , Feng Yang , Rosillon Dominique , Guignard Adrienne
Published: October 2019

Objective

Assess the risk of progression to cirrhosis and hepatocellular carcinoma (HCC) due to hepatitis B virus (HBV)-infection in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).

Methods

Retrospective cohort study in the UK Clinical Practice Research Datalink with three cohorts: subjects with T2DM and HBV infection (T2DM+HBV cohort; N = 297), with T2DM without HBV-infection (T2DM cohort; N = 261 865), and with HBV-infection without T2DM (HBV cohort; N = 3630). Primary analyses were performed on the three cohorts and secondary analyses on subcohorts including patients with NAFLD diagnosis code (N = 6599). Case/outcome definitions were formulated with International Classification of Diseases/Read codes/laboratory results and classified using validated algorithms. Adjusted incidence rate ratios (IRR) were estimated with a Poisson regression model.

Results

When comparing the T2DM+HBV and T2DM cohorts, adjusted IRRs were 14.06 (95% confidence interval: 4.47–44.19) for cirrhosis and 2.83 (1.06–7.55) for HCC. When comparing the T2DM+HBV and HBV cohorts, adjusted IRRs were 0.68 (0.21–2.27) for cirrhosis and 1.39 (0.46–4.20) for HCC. No cirrhosis cases were identified in T2DM+NAFLD+HBV patients; IRs were 16.92/10 000 person-years (12.97–21.69) and 85.24/10 000 person-years (10.32–307.91) in the T2DM+NAFLD and NAFLD+HBV cohorts.

Conclusion

HBV-infection increased significantly the risk for cirrhosis among T2DM patients, however, not beyond the expected incremental risk among infected non-T2DM subjects. Our approach to evaluate the role of T2DM/NAFLD and HBV-infection in liver disease progression could be applied to other settings with higher HBV prevalence.
Increased odds of cholangiocarcinoma in Hispanics: results of a nationwide analysis
Authors: Ruiz Jorge Nicolas , Kröner Paul T. , Wijarnpreecha Karn , Corral Juan E. , Harnois Denise M. , Lukens Frank J.
Published: October 2019

Objective

Cholangiocarcinoma (CCA) affects all ethnicities worldwide. The Hispanic population being the leading ethnic minority in the United States, its importance to the healthcare system cannot be understated. This study aims to assess the occurrence and outcomes of CCA in Hispanic patients in the United States.

Methods

This is a case-control study using the National Inpatient Sample 2014. All patients with ICD-9 CM codes for CCA were included. Hispanic patients were identified from the ethnic categories within the database. The primary outcomes were the occurrence and odds of CCA in the Hispanic population when compared with other ethnicities. Secondary outcomes were inpatient mortality, morbidity, ICU stay, multiorgan failure, and resource utilization.

Results

A total of 13 965 patients with CCA were identified, of which 2750 were propensity-matched to controls (1480 Hispanic). The inpatient occurrence of CCA in Hispanics relative to the national population was 2.73/100 000 persons, compared to 4.82/100 000 persons (39.9/100 000 relative to inpatient population) of all other ethnicities. After adjusting for confounders on multivariate analysis, Hispanic patients displayed adjusted propensity-matched odds of 1.28 (P < 0.01) of having CCA when compared with other ethnicities. Hispanics did not display different propensity-matched odds of inpatient mortality, morbidity, hospital length of stay, or resource utilization compared to non-Hispanic patients.

Conclusion

This study demonstrated that the odds of CCA in admitted patients are higher for the Hispanic population. This difference with the prevalence potentially suggests the presence of social factors such as disparities in cancer prevention or detection in this group.
Recurrence of spontaneous bacterial peritonitis in cirrhosis: novel predictors
Authors: Abdel-Razik Ahmed , Abdelsalam Mostafa , Gad Doaa F. , Abdelwahab Ahmed , Tawfik Mona , Elzehery Rasha , Elhelaly Rania , Hasan Ahmad S. , El-Wakeel Niveen , Eldars Waleed
Published: October 2019

Background and aims

Recurrence of spontaneous bacterial peritonitis (SBP) is still a matter of debate. We conducted this study to evaluate the probable factors that predict the recurrence of SBP in patients who recovered from the first episode of SBP and the long-term outcomes of SBP recurrence.

Methods

One hundred twenty-four patients diagnosed with liver cirrhosis, SBP and did not receive secondary prophylaxis either with norfloxacin or other antibiotics were included in this prospective cohort pilot study. Clinical, biochemical and ascitic fluid analysis parameters were evaluated. Ascitic fluid interferon-γ-induced protein (IP-10), calprotectin, interleukin-6 and tumor necrosis factor-α were measured by ELISA.

Results

Of these, 76 patients survived with an in-hospital mortality rate of 38.7%. The survivors were classified into two groups according to recurrence and nonrecurrence of SBP and survival time, clinical parameters and cause of death were investigated. Thirty-one participants had one or more attacks of SBP, with a recurrence rate of 40.8% within one-year follow-up. Before discharge, multivariate analysis showed that ascitic IP-10 (≥1220 pg/ml), ascitic calprotectin (≥550 ng/ml), serum albumin (≤2.5 g/dl), nonuse of prophylactic β-blockers and use of proton-pump inhibitors (PPIs) were the independent variables in predicting recurrent SBP. Sepsis-related organ failure was the most common etiology of mortality in the recurrent SBP group within 3 and 6 months.

Conclusion

Increased ascitic calprotectin and IP-10, hypoalbuminemia, nonuse of prophylactic β-blockers and use of PPI were independently associated with increased SBP recurrence rate. Sepsis-related organ failure was the most common etiology of mortality.
High-Tech/High-Touch Nursing Care in the Genomic Era
Authors: Ponte Patricia Reid
Published: October 2019

In this column, nurse practitioner, educator, and scientist Dr Andrew Dwyer describes his program of translational research aimed at advancing nurses' crucial role in delivering person-centered care and engaging consumers to make informed decisions for genetic testing that are in line with their values and preferences.
Why Cities Survive and Companies Die
Authors: Clancy Thomas R.
Published: October 2019

As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on the application of management strategies in health systems. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This article is the 5th in a series of articles that focuses on why technological complexity is increasing and strategies nurse administrators can use to successfully implement change in the face of it.
Health Equity—Caring for the Indigent—A Nursing Specialty
Authors: Reid Ponte Patricia
Published: October 2019

In this month's Inspiration Point, Dr Patricia Reid Ponte interviews Dr Karen Bankston, PhD, MSN, FACHE.