bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate Inversions: Going beyond Tax Incentives
Authors: Col Burcin , Liao Rose , Zeume Stefan
Published: October 2019

We study tax and nontax incentives for corporate inversions in a hand-collected data set of 691 inversions out of 11 home countries into 45 host destinations over the 1996–2013 period. Even though lower tax rates generally attract inversions, only 2 of 5 firms invert into tax havens, and two-thirds of firms invert into host destinations with lower statutory tax rates than those faced at home. Moreover, firms invert to geographically close destinations with similar governance standards. Using staggered country-pair-level policy changes as experiments, we find that host-country governance may explain why not all firms invert.

Received December 6, 2018; Editorial decision August 12, 2019 by Editor Andrew Ellul.
The effect of methotrexate on tumour necrosis factor concentrations in etanercept-treated rheumatoid arthritis patients
Authors: Berkhout Lea C , l’Ami Merel J , Krieckaert Charlotte L M , Vogelzang Erik H , Kos Dorien , Nurmohamed Michael T , Wolbink Gerrit J , Rispens Theo
Published: October 2019

Objectives

Recently, we demonstrated that early low concentrations of circulating, adalimumab-bound TNF in RA patients treated with adalimumab was associated with future anti-drug antibody formation. Furthermore, low TNF was associated with less frequent baseline MTX use. This is remarkable, because of the anti-inflammatory effects of MTX and a potential inhibiting effect on cytokine production. We hypothesized an indirect effect of non-MTX use on low TNF concentrations via immunogenicity. To investigate the effect of MTX on TNF concentrations independent of anti-drug antibody formation, we measured TNF in RA patients treated with etanercept, a drug with low immunogenicity.

Methods

TNF was quantified in 186 consecutive etanercept-treated RA patients at baseline and at weeks 4, 16 and 28. The dynamics of TNF during etanercept treatment were compared with dynamics recently published for adalimumab.

Results

We demonstrated that TNF concentrations at week 4 did not associate with baseline MTX or remission after 28 weeks. Furthermore, median (interquartile range) TNF increased from <112 (<112–<112) pg/ml at baseline to 548 (344–688) pg/ml at week 4 and remained stable at week 16 and 28 [598 (442–756) and 568 (444–755) pg/ml, respectively].

Conclusion

Circulating TNF did not associate with MTX usage in etanercept-treated patients. This implies that MTX does not have a direct effect on TNF concentrations in circulation and that the association between early low TNF and non-use of MTX for adalimumab is thus most likely due to anti-drug antibody formation.
Neural correlates of up-regulating positive emotions in fMRI and their link to affect in daily life
Authors: Grosse Rueschkamp Johanna M , Brose Annette , Villringer Arno , Gaebler Michael
Published: October 2019

Emotion regulation is typically used to down-regulate negative or up-regulate positive emotions. While there is considerable evidence for the neural correlates of the former, less is known about the neural correlates of the latter—and how they are associated with emotion regulation and affect in daily life. Functional magnetic resonance imaging (fMRI) data were acquired from 63 healthy young participants (22 ± 1.6 years, 30 female), while they up-regulated their emotions to positive and neutral images or passively watched them. The same participants’ daily affect and emotion regulation behavior was measured using experience sampling over 10 days. Focusing on the ventral striatum (VS), previously associated with positive affective processing, we found increased activation during the up-regulation to both positive and neutral images. VS activation for the former positively correlated with between- and within-person differences in self-reported affective valence during fMRI but was not significantly associated with up-regulation in daily life. However, participants with lower daily affect showed a stronger association between changes in affect and activation in emotion-related (medial frontal and subcortical) regions—including the VS. These results support the involvement of the VS in up-regulating positive emotions and suggest a neurobehavioral link between emotion-related brain activation and daily affect.
Making sense together: The role of scientists in the coproduction of knowledge for policy making
Authors: Adelle Camilla , Pereira Laura , Görgens Tristan , Losch Bruno
Published: October 2019

New forms of knowledge production that actively engage in different types of knowledge in participatory settings have emerged in the last two decades as ‘the right thing to do’. However, the role scientists play in facilitating these processes remains unclear. This article contributes to calls for more deliberate and critical engagement between scholarship and practice of the co-production of knowledge by constructing and testing a conceptual framework based on the literature outlining specific task for scientists in co-production processes. This framework is used to analyze the co-production of knowledge for local food security policy in South Africa, based on documentary analysis and in-depth interviews with scientists, policy makers and stakeholders. It shows that the tasks set out in the conceptual framework provide a useful lens for unpacking, and so better understanding, the role played by scientists in knowledge co-production. Applying the framework also helps to uncover insights into proximate outcomes of co-production, such as increased capacity and power redistribution, as well as critical contextual factors, such as the type of policy problem and the prevailing governance framing. The article concludes that more nuanced and critical understanding of the role of scientists in the co-production process will help over-come the apparent paradox that, although co-production is a ‘buzz word’, researchers often they still adhere to objective and linear knowledge production.
Impact of type 1 diabetes mellitus, glucose levels, and glycemic control on sleep in children and adolescents: a case–control study
Authors: Macaulay Grace C , Galland Barbara C , Boucher Sara E , Wiltshire Esko J , Haszard Jillian J , Campbell Angela J , Black Stephanie M , Smith Claire , Elder Dawn , Wheeler Benjamin J
Published: October 2019

Study Objectives

To assess differences in habitual sleep patterns and sleep states between children and adolescents with type 1 diabetes mellitus (T1DM) and control subjects, and to explore the relationships between sleep, glucose levels, and glycemic control.

Methods

Participants included 82 children (5–18 years); 41 with T1DM (cases), and 41 healthy control subjects group matched for age and sex. Sleep was measured by 7-day actigraphy and single-night home-based polysomnography (PSG) recordings. Hemoglobin A1c (HbA1c) and 7 days of continuous glucose monitoring (CGM) data were collected in cases. Regression analyses were used to model all within- and between-group comparisons adjusted for age, sex, and BMI z-scores.

Results

There were no significant differences in sleep duration, efficiency, or awakenings as measured by actigraphy and PSG between cases and controls, nor sleep states measured by PSG. However, cases had significantly later sleep onset and offset than controls (both p < 0.05), partially moderated by age. Cases with suboptimal glycemic control (HbA1c ≥ 58 mmol/mol [≥7.5%]) had significantly shorter actigraphy-derived total sleep time (TST) (mean difference = −40 minutes; 95% confidence interval = −77, −3), with similar differences in TST measured by PSG. Cases with mean CGM glucose levels ≥10 mmol/L (≥180 mg/dL) on PSG night had significantly more stage N3 (%) sleep and less stage REM (%) sleep (both p < 0.05).

Conclusions

Short- and long-term suboptimal glycemic control in T1DM children appears to be associated with sleep alterations. Pediatric diabetes care teams should be aware of potential interrelationships between sleep and T1DM, including management and glycemic control.
Deciphering Adverse Outcome Pathway Network Linked to Bisphenol F Using Text Mining and Systems Toxicology Approaches
Authors: Rugard Marylène , Coumoul Xavier , Carvaillo Jean-Charles , Barouki Robert , Audouze Karine
Published: October 2019

Bisphenol F (BPF) is one of several Bisphenol A (BPA) substituents that is increasingly used in manufacturing industry leading to detectable human exposure. Whereas a large number of studies have been devoted to decipher BPA effects, much less is known about its substituents. To support decision making on BPF’s safety, we have developed a new computational approach to rapidly explore the available data on its toxicological effects, combining text mining and integrative systems biology, and aiming at connecting BPF to adverse outcome pathways (AOPs). We first extracted from different databases BPF-protein associations that were expanded to protein complexes using protein-protein interaction datasets. Over-representation analysis of the protein complexes allowed to identify the most relevant biological pathways putatively targeted by BPF. Then, automatic screening of scientific abstracts from literature using the text mining tool, AOP-helpFinder, combined with data integration from various sources (AOP-wiki, CompTox, etc.) and manual curation allowed us to link BPF to AOP events. Finally, we combined all the information gathered through those analyses and built a comprehensive complex framework linking BPF to an AOP network including, as adverse outcomes, various types of cancers such as breast and thyroid malignancies. These results which integrate different types of data can support regulatory assessment of the BPA substituent, BPF, and trigger new epidemiological and experimental studies.
Characterization of the Complete Genome and P0 Protein for a Previously Unreported Genotype of Cotton Leafroll Dwarf Virus, an Introduced Polerovirus in the United States
Authors: Avelar Sofia , Ramos-Sobrinho Roberto , Conner Kassie , Nichols Robert L. , Lawrence Kathy , Brown Judith K.
Published: October 2019

Virus-like disease symptoms consisting of leaf cupping, shortened internodes, and overall stunting were observed in commercial cotton fields in Alabama in 2017 to 2018. To determine the complete genome sequence of the suspected causal polerovirus, symptomatic leaf samples were collected in Macon County, Alabama, and subjected to Illumina RNA sequencing. Based on BLASTn analysis, the Illumina contig of 5,771 nt shared the highest nucleotide identity (approximately 95%) with members of the species Cotton leafroll dwarf virus (CLRDV) (genus Polerovirus; family Luteoviridae) from Argentina and Brazil. The full-length viral genome sequence was verified by reverse transcription (RT)-PCR amplification, cloning, and Sanger sequencing. The complete CLRDV genome of 5,865 nt in length shared 94.8 to 95.2% nucleotide identity with six previously reported CLRDV isolates. The genome of the CLRDV isolate amplified from Alabama samples (CLRDV-AL) has seven predicted open reading frames (ORFs). Viral proteins 1 to 5 (P1 to P5) shared 91.9 to 99.5% amino acid identity with the six CLRDV isolates from Argentina and Brazil. However, P0, the suppressor of host gene silencing, shared 82.4 to 88.5% pairwise amino acid identity with the latter CLRDV isolates. Phylogenetic analysis of the seven full-length CLRDV genomes resolved three sister clades: CLRDV-AL, CLRDV-typical, and CLRDV-atypical, respectively. Three recombination events were detected by the recombination detection program among the seven CLRDV isolates with breakpoints occurring along the genome. Pairwise nucleotide identity comparisons of ORF0 sequences for the three CLRDV-AL field isolates indicated that they were >99% identical, suggesting that this previously unknown CLRDV genotype represents a single introduction to Alabama.
Revisiting Seed Transmission of the Type Strain of Tomato yellow leaf curl virus in Tomato Plants
Authors: Pérez-Padilla Verónica , Fortes Isabel M. , Romero-Rodríguez Beatriz , Arroyo-Mateos Manuel , Castillo Araceli G. , Moyano Cristina , De León Leandro , Moriones Enrique
Published: October 2019

Isolates of the Tomato yellow leaf curl virus (TYLCV) species (genus Begomovirus, family Geminiviridae) infect tomato crops worldwide, causing severe economic damage. Members of the whitefly Bemisia tabaci sibling species group are the vector of begomoviruses, including TYLCV. However, transmission of isolates of the type strain (Israel [IL]) of TYLCV (TYLCV-IL) by tomato seed has recently been reported based on infections occurring in Korea. Because of the consequences of this finding on the epidemiology and control of the disease caused by TYLCV and on the seed market, it was considered essential to revisit and expand those results to other tomato-growing areas. TYLCV DNA content was detected in tomato and Nicotiana benthamiana seed collected from plants naturally or experimentally infected with TYLCV-IL, supporting its seedborne nature. The TYLCV-IL replication detected in tomato and N. benthamiana flower reproductive organs demonstrated close association of this virus with the seed during maturation. However, the significant reduction of TYLCV DNA load after surface disinfections of tomato seed suggests that most of the virus is located externally, as contaminant of the seed coat. Transmission assays, carried out with seven tomato genotypes and more than 3,000 tomato plants, revealed no evidence of seed transmission from “surface-disinfected” or untreated seed for two Mediterranean isolates of TYLCV-IL. Similar results were also obtained for seed collected from TYLCV-IL-infected N. benthamiana plants. The results support the conclusion that TYLCV-IL is seedborne but is not seed transmitted in tomato or N. benthamiana, suggesting that transmission through seed is not a general property of TYLCV.
AMPK β1 activation suppresses antipsychotic‐induced hyperglycemia in mice
Authors: Shamshoum Hesham , Medak Kyle D. , Townsend Logan K. , Ashworth Kristen E. , Bush Natasha D. , Halm Margaret K. , Kemp Bruce E. , Wright David C.
Published: October 2019

Olanzapine (OLZ) is a second‐generation antipsychotic that is used to treat schizophrenia but also causes acute hyperglycemia. This study aimed to determine if the ablation of AMPK β1‐containing complexes potentiates acute OLZ‐induced metabolic dysfunction and if the activation of AMPK β1 suppresses these effects. Female AMPK β1‐/‐ or wild‐type (WT) control mice were treated with OLZ, and changes in bloodglucose, serum and liver metabolites, whole‐body fuel oxidation, and pyruvate‐induced increases in blood glucose were measured. Additionally, WT mice were cotreated with OLZ and A769662, a specific AMPK β1 activator, and we determined if cotreatment protected against acute, OLZ‐induced metabolic dysfunction. OLZ‐induced increases in blood glucose were exacerbated in AMPK β1‐/‐ mice compared with WT mice, and this was paralleled by greater OLZ‐induced increases in markers of liver glucose production, such as pyruvate tolerance, serum glucagon, and glucagon responsiveness. Cotreatment with A769662 attenuated OLZ‐induced increases in blood glucose, serum nonesterified fatty acid, and glycerol. Furthermore, this effect was absent in AMPK β1‐/‐ mice, consistent with A769662's specificity for the AMPK β1 subunit. Reductions in AMPK activity potentiate the effects of acute OLZ treatment on blood glucose, whereas specifically targeting AMPK β1‐containing complexes is sufficient to protect against OLZ‐induced hyperglycemia.—Shamshoum, H., Medak, K. D., Townsend, L. K., Ashworth, K. E., Bush, N. D., Hahn, M. K., Kemp, B. E., Wright, D. C. AMPK β1 activation suppresses antipsychotic‐induced hyperglycemia in mice. FASEB J. 33, 14010‐14021 (2019). www.fasebj.org
Evaluating the Effect of Training Along With Fit Testing on Premolded Earplug Users in a Chinese Petrochemical Plant
Authors: Liu Yufei , Gong Wei , Liu Xin , Li Ling
Published: October 2019

Objectives:

To gain insight into the current practice of hearing protection of Chinese workers and the value of hearing protection device (HPD) fit testing.

Design:

HPD fit testing was conducted on workers (N = 774) in a petrochemical plant in Eastern China who were on duty during the period of this study. The 3M E-A-Rfit Dual-Ear Validation System was used to measure the personal attenuation ratings (PARs) of a premolded earplug used at the work site. Repeated fit testing was conducted at approximately 6- or 12-month intervals. Wilcoxon signed rank tests were conducted to analyze the pairwise differences between the baseline, postintervention, and follow-up visit PARs, and Mann–Whitney tests were used to compare the PARs obtained by two follow-up groups.

Results:

The median PAR baseline was 11 dB; significant improvement was shown on the postintervention PARs (p < 0. 001). No significant difference was shown between PARs obtained during the 6- and 12-month follow-up visits (p > 0.05). Comparing PARs of follow-up visits with the baseline PAR demonstrated a significant improvement (p < 0. 001), but revealed a significant decline (p < 0. 001) comparing with the postintervention PARs.

Conclusions:

HPD fit testing showed value added as to verify the sufficiency of attenuation. The training along with fit testing showed contributions to improve PARs, maintained effectiveness over time, and assisted in HPD selection. Follow-up is believed to be important to ensure that the HPDs are continually used correctly. There was no significant difference in the sustained effectiveness of the follow-up when observe 6- and 12-month subsequent to intervention.
CUDC-101 overcomes arsenic trioxide resistance via caspase-dependent promyelocytic leukemia-retinoic acid receptor alpha degradation in acute promyelocytic leukemia
Authors: Zhang Tianzhuo , Ma Dan , Wei Danna , Lu Tingting , Yu Kunlin , Zhang Zhaoyuan , Wang Weili , Fang Qin , Wang Jishi
Published: October 2019

Although arsenic trioxide (ATO) treatment has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, many high-risk APL patients who fail to achieve a complete molecular remission or relapse become resistant to ATO. Herein, we report that 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) exhibits specific anticancer effects on APL and ATO-resistant APL in vitro and in vivo, while showing negligible cytotoxic effect on the noncancerous cells including normal CD34+ cells and bone marrow mesenchymal stem cells from APL patients. Further mechanistic studies show that CUDC-101 triggers caspase-dependent degradation of the promyelocytic leukemia-retinoic acid receptor alpha fusion protein. As a result, APL and ATO-resistant APL cells undergo apoptosis upon CUDC-101 treatment and this apoptosis-inducing effect is even stronger than that of ATO. Finally, using a xenograft mouse model, we demonstrated that CUDC-101 significantly represses leukemia development in vivo. In conclusion, these results suggested that CUDC-101 can serve as a potential candidate drug for APL, particularly for ATO-resistant APL.
Definitive Radiation Treatment Patterns and Outcomes for Low and Intermediate Risk Prostate Cancer Patients
Authors: Asamoah Francis A. , Yarney Joel , Awasthi Shivanshu , Vanderpuye Verna , Dadzie Mary A. , Fink Angelina , Naghavi Arash O. , Abrahams Afua , Mensah James E. , Sasu Evans , Tagoe Samuel N. , Dhillon Jasreman , Johnstone Peter A.S. , Yamoah Kosj
Published: October 2019

Purpose:

To evaluate early-stage prostate cancer (PCa) radiotherapy treatment patterns and outcomes among Ghanaian men (GM) compared with US men (USM).

Materials and Methods:

This retrospective study consists of 987 National Comprehensive Cancer Network low risk, favorable intermediate risk, and unfavorable intermediate risk PCa patient subgroups; GM (173) and USM (814). Differences in baseline covariates and clinical characteristics between GM and USM were analyzed using χ2 and Mann-Whitney test while Cox Proportional Hazards model was used to assess freedom from biochemical failure differences between the study groups.

Results:

Median follow-up for this study was 40 months. GM were diagnosed at a younger median age (64 vs. 68 y, P<0.001) with heavier unfavorable intermediate risk disease burden (32.4% vs. 19.2%) compared with USM. Significant differences were identified in median external beam radiotherapy dose (72.4 vs. 78 Gy, P<0.001); brachytherapy utilization (49.7% vs. 80.6%, P<0.001) and androgen deprivation therapy for intermediate risk disease (48.4% vs. 21.0%, P<0.001) between GM and USM, respectively. GM with low risk and favorable intermediate risk PCa were at increased risk of biochemical recurrence compared with USM with adjusted hazard ratio: 5.15 (1.27 to 20.7), P=0.02 and 4.64 (1.20 to 17.92), P=0.02, respectively.

Conclusions:

Compared with USM, GM with low and favorable intermediate risk PCa may experience less durable disease control following standard treatment recommendations. Results suggest differences in radiation treatment and possible inherent differences between the 2 populations. This data will aid in developing research strategies to improve treatment outcomes in GM.
Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups
Authors: Kayser Angela , Beck Evelin , Hoeltzenbein Maria , Zinke Sandra , Meister Reinhard , Weber-Schoendorfer Corinna , Schaefer Christof
Published: October 2019

Objectives:

Our aim was to evaluate the effects of beta-blockers during the second and third trimester on fetal growth, length of gestation and postnatal symptoms in exposed infants.

Methods:

The current prospective observational cohort study compares 294 neonates of hypertensive mothers on metoprolol or bisoprolol during the second and/or third trimester with 225 methyldopa-exposed infants and 588 infants of nonhypertensive mothers. The risks for reduced birth weight, prematurity, neonatal bradycardia, hypoglycaemia and respiratory disorders were analysed.

Results:

The rate of small-for-gestational-age children was significantly higher in long-term beta-blocker exposed infants (24.1%) compared with the methyldopa cohort [10.2%, odds ratio (OR)adj 2.5, 95% confidence interval (CI) 1.2–5.2] and the nonhypertensive cohort (9.9%, ORadj 4.3, 95% CI 2.6–7.1). The risk for preterm birth was significantly increased compared with nonhypertensive pregnancies (ORadj 2.2, 95% CI 1.3–3.8) but not compared with the methyldopa cohort. Neonatal adverse outcomes occurred more frequently in the study cohort (11.5%) compared with the nonhypertensive comparison group (6.5%) and the methyldopa cohort (8.4%), but without statistical significance (ORadj 1.5, 95% CI 0.7–3.0 and ORadj 1.5, 95% CI 0.7–3.3, respectively).

Conclusion:

Long-term intrauterine exposure to metoprolol or bisoprolol may increase the risk of being born small-for-gestational-age. It is still a matter of debate to which extent maternal hypertension contributes to the lower birth weight. Serious neonatal symptoms are rare. Altogether, metoprolol and bisoprolol are well tolerated treatment options, but a case-by-case decision on close neonatal monitoring is recommended.
Muscle strength is a major determinant of the blood pressure response to isometric stress testing: the Asklepios population study
Authors: Van daele Caroline M. , Chirinos Julio A. , De Meyer Tim , De Buyzere Marc L. , Langlois Michel R. , Bekaert Sofie , Segers Patrick , Gillebert Thierry C. , Rietzschel Ernst R.
Published: October 2019

Aim:

Maximal handgrip strength is a strong predictor of cardiovascular mortality in economically and socioculturally diverse countries, yet the main determinants of cardiovascular response to change in afterload during handgrip are not well known. We examined the blood pressure (BP) responses during submaximal handgrip (at 25% of grip strength) and the determinants of grip strength.

Methods:

We studied 2215 participants from a population-based random sample without overt clinical disease (Asklepios Study; mean age 56.2 years). Handgrip testing was performed using a modified Jamar dynamometer with direct visual feedback. Simultaneously, a validated finger plethysmographic device measured continuous BP and heart rate.

Results:

During handgrip, SBP and DBP rose by, respectively, 20 ± 13 and 10 ± 6 mmHg. These changes were normally distributed and consistently higher in men. The main independent determinants of mean arterial pressure response during handgrip were: grip strength (F = 191.4; P < 0.001), baseline pulse pressure (F = 32.0; P < 0.001), height (F = 16.4; P < 0.001) and age (F = 12.8; P < 0.001). Grip strength was associated with muscle mass, better metabolic health, but also with higher baseline DBP. There was a significant graded increase in maximum pressure achieved and in the magnitude of pressure change during handgrip with increasing BP categories (P for trend <0.001).

Conclusion:

The population BP response to handgrip is variable and its predominant determinant turned out to be grip strength itself, which should be accounted for in future analyses. Higher baseline BP, even within the normotensive range, acted as an independent and graded predictor of BP increase during handgrip.
Visit-to-visit blood pressure variation and outcomes in heart failure with reduced ejection fraction: findings from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial
Authors: Monzo Luca , Ferreira João Pedro , Abreu Paula , Szumski Annette , Böhm Michael , McMurray John J.V. , Pitt Bertram , Swedberg Karl , van Veldhuisen Dirk J. , Girerd Nicolas , Vincent John , Zannad Faiez , Rossignol Patrick
Published: October 2019

Background:

Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV.

Methods and results:

We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62–2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the ‘normal’ range.

Conclusion:

In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure.

ClinicalTrials.gov identifier:

NCT00232180.
Cancer patients with potential eligibility for vascular endothelial growth factor antagonists use have an increased risk for cardiovascular diseases comorbidities
Authors: Liu Fei , Hidru Tesfaldet H. , Gao Ruiyuan , Lin Yajuan , Liu Ying , Fang Fengqi , Liu Jiwei , Li Huihua , Yang Xiaolei , Xia Yunlong
Published: October 2019

Background:

Recent studies have reported the prevalence of cardiovascular diseases (CVDs) among cancer patients following the use of the vascular endothelial growth factor (VEGF) signaling inhibitors. However, data for patients with a history of cancer before active cancer treatment are lacking. This study aims to investigate the distribution of CVD-related comorbidities before cancer treatment in potential VEGF antagonists candidates.

Methods:

A total of 22 500 newly diagnosed cancer patients registered from 1 January 2011 to 31 December 2017 were included. Cancer patients with colorectal cancer (CRC), renal cell carcinoma (RCC), thyroid cancer, hepatocellular carcinoma (HCC), and lung cancer were selected.

Results:

Hypertension (HTN), coronary heart diseases, atrial fibrillation, and heart failure were top CVD comorbidities among studied cancers. HTN was the most prevalent CVD (26.0%). The prevalence of HTN in RCC, CRC (33.5 and 29.4% respectively) was significantly higher than that in HCC, lung cancer, and thyroid cancer patients (25.1, 24.5, and 23.1%, respectively). Among cancer patients with HTN, the majority of cancer patients fall in grade III (75.7%) and very high cardiovascular risk level (85.4%). Out of the 5847 HTN patients, 26% were not in antihypertensive use, and 34.2% failed to achieve the target blood pressure.

Conclusion:

Cancer patients carry a high burden of CVD-related comorbidities before the application of VEGF antagonists. HTN is the most prevalent comorbid condition, and cancer patients with HTN constitute substantial cardiovascular risks and a higher co-prevalence of other CVDs.
Translating Data From an Electronic Prescribing and Medicines Administration System Into Knowledge
Authors: Van Wilder Astrid , Spriet Isabel , Van Eldere Johan , Peetermans Willy E. , Vanhaecht Kris , Vandersmissen Jo , Artois Martine , Gilis Karin , Vanautgaerden Pieter , Balcaen Koen , Rademakers Frank E. , Bruyneel Luk
Published: October 2019

Background:

Electronic Prescribing and Medicines Administration (EPMA) systems are being widely implemented to facilitate medication safety improvement. However, translating the resulting big data into actionable knowledge has received relatively little attention.

Objective:

The objective of this study was to use routinely collected EPMA data in the study of exact time discrepancy between physicians’ order and nurses’ administration of systemic antibiotics. We evaluated first and follow-up dose administration and dose intervals and examined multifactorial determinants in ordering and administration explaining potential discrepancy.

Methods:

We conducted an observational study of electronic health records for all medical patient stays with antibiotic treatment from January to June 2018 (n=4392) in a large Belgian tertiary care hospital. Using an EPMA system with Barcode Medication Administration, we calculated time discrepancy between order and administration of first doses (n=6233), follow-up doses (n=87 960), and dose intervals. Multiple logistic regression analysis estimated the association between time discrepancy and various determinants in ordering and administration.

Results:

Time discrepancy between physician order and nurse administration was <30 minutes for 48.7% of first doses and 61.7% of follow-up doses, with large variation across primary diagnoses. Greater dose intervals, oral versus intravenous administration, and order diversion from regular nurse administration rounds showed strongest association with less timely administration.

Conclusions:

EPMA systems show huge potential to generate actionable knowledge. Concerning antibiotic treatment, having physicians’ orders coincide with regular nurse administration rounds whenever clinically appropriate, further taking contextual factors into account, could potentially improve antibiotic administration timeliness.
Persistent Disparities in Medicare’s Annual Wellness Visit Utilization
Authors: Lind Kimberly E. , Hildreth Kerry L. , Perraillon Marcelo Coca
Published: October 2019

Introduction:

The Medicare Annual Wellness Visit (AWV) is a preventive care visit introduced in 2011 as part of the Affordable Care Act provided without cost to beneficiaries. The AWV is associated with higher preventive services utilization. Although AWV utilization increased during 2011–2013, utilization was lower among ethnoracial minority beneficiaries who may benefit the most.

Objectives:

To determine if AWV utilization disparities have persisted using the most recent data available.

Research Design:

The authors analyzed AWV utilization in 2011–2013 and 2015–2016 by beneficiary-reported race and ethnicity, adjusting for potential confounders.

Subjects:

Weighted sample of 78,639,501 fee-for-service Medicare beneficiaries aged 66 years and older who participated in the Medicare Current Beneficiary Survey 2011–2013 or 2015–2016.

Measures:

AWV utilization was identified using Medicare claims.

Results:

AWV utilization increased from 8.1% to 23.0% of all beneficiaries between 2011 and 2016. Compared with non-Hispanic white beneficiaries, utilization was significantly lower among non-Hispanic Black and non-Hispanic other race beneficiaries in both the minimally and fully-adjusted models. Hispanic/Latino beneficiaries had lower utilization in the minimally adjusted model, but not in the fully-adjusted model. In 2016, compared with non-Hispanic white beneficiaries, AWV utilization was 10.2 points lower for non-Hispanic black, 11.6 points lower for Hispanic/Latino, and 8.6 points lower for non-Hispanic other race beneficiaries, and these differences were attenuated after adjusting for all covariates to 6.8 points lower, 9.4 points lower, and 7.2 points lower, respectively.

Conclusions:

The AWV has the potential to increase the use of preventive care, improve health, and reduce ethnoracial disparities among Medicare beneficiaries, but realizing these goals will require increasing utilization by minority groups. If ethnoracial minority beneficiaries had used the AWV at the same rate as non-Hispanic white beneficiaries during the study period, then ~1.6 million additional AWVs would have been used.
Intraobserver and interobserver agreement for the interpretation of 68Ga–prostate-specific membrane antigen-I&T positron emission tomography/computed tomography imaging
Authors: Gültekin Aziz , Yaylalı Olga , Şengöz Tarık , Yüksel Doğangün , Şahin Beyza
Published: October 2019

Objectives

The use of 68Ga–prostate-specific membrane antigen positron emission tomography/computed tomography is spreading due to its clinical benefits. In this study, we aim to determine the intra- and interobserver agreement levels of 68Ga– prostate-specific membrane antigen-I&T positron emission tomography/computed tomography according to molecular imaging tumor-lymph node-metastases reporting system.

Materials and methods

Eighty prostate cancer patients and underwent 68Ga– prostate-specific membrane antigen positron emission tomography/computed tomography were blindly evaluated twice by four nuclear medicine specialists at intervals of 4 weeks. The evaluations were performed according to molecular imaging tumour-lymph node-metastases (miTNM) classification. We used Cohen’s Kappa and Fleiss’ Kappa analysis to analyse intra- and interobserver agreements.

Results

When 68Ga–prostate-specific membrane antigen positron emission tomography/computed tomography findings were evaluated according to miTNM classification, the obtained kappa values were as follows. The intraobserver Cohen’s kappa coefficient was found to be 0.79 (substantial agreement), 0.93 (almost perfect agreement), and 0.94 (almost perfect agreement) for miT, miN, and miM, respectively. During interobserver evaluation between the four observers, the kappa coefficient was 0.52 (moderate agreement) for miT, 0.74 (substantial agreement) for miN, and 0.84 (almost perfect agreement) for miM.

Conclusion

There is no research on the intraobserver agreement analysis of 68Ga–prostate-specific membrane antigen positron emission tomography/computed tomography in the literature. Our findings are the first ones. The intraobserver agreement was almost perfect. Moreover, although 68Ga–prostate-specific membrane antigen I&T positron emission tomography/computed tomography had moderate interobserver evaluation compliance of the primary tumour, it had excellent interobserver agreement levels in local lymph node metastasis and distant metastasis evaluation.4012501255
Nutritionist Guide to Direct-to-Consumer Genetic Tests and Precision Nutrition
Authors: Dashti Hassan S. , Tucker Chandler
Published: October 2019

Analogous to precision medicine, precision nutrition aims to tailor nutritional recommendations based on personal needs to optimize health. The field of nutritional genomics, which refers to the bidirectional interplay between dietary nutrients and the genome, is providing some of the necessary scientific evidence for precision nutrition. However, the extent of the clinical utility of nutritional genomics largely depends on the mode of disease/trait inheritance and remains unclear for prevalent, complex diseases, such as obesity, heart disease, and type 2 diabetes. Because genomic technology is now readily accessible through affordable personal DNA tests, it is now critical for nutritionists to establish a basic understanding in nutritional genomics to evaluate the validity of genetics-related “health claims” being provided by direct-to-consumer genetic testing companies. In this review, we provide examples of successful nutritional genomics studies, review current limitations, provide guidelines to evaluate health claims, and lastly discuss possible avenues and future outlooks for precision nutrition.
Nutritional Considerations for Wrestlers
Authors: Stanzione Joseph R. , Volpe Stella Lucia
Published: October 2019

Wrestling is a combat sport with weight-based categorizations. These athletes commonly attempt to reduce their body weight to qualify for lower-weight classes. Wrestlers often subject themselves to periods of low energy intake and high energy expenditure, exposing them to a prolonged energy deficit. Therefore, nutritional considerations for these athletes are complex. This review will enlighten sports professionals, and those working closely with wrestlers, about the nature of the sport. In addition, we offer some guidance for wrestlers to consider.
Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP)
Authors: Cheung Carol C. , Barnes Penny , Bigras Gilbert , Boerner Scott , Butany Jagdish , Calabrese Fiorella , Couture Christian , Deschenes Jean , El-Zimaity Hala , Fischer Gabor , Fiset Pierre O. , Garratt John , Geldenhuys Laurette , Gilks C. Blake , Ilie Marius , Ionescu Diana , Lim Hyun J. , Manning Lisa , Mansoor Adnan , Riddell Robert , Ross Catherine , Roy-Chowdhuri Sinchita , Spatz Alan , Swanson Paul E. , Tron Victor A. , Tsao Ming-Sound , Wang Hangjun , Xu Zhaolin , Torlakovic Emina E.
Published: October 2019

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.
Primary Ovarian High-grade Neuroendocrine Carcinoma With Merkel Cell–like Immunophenotype Arising in a Teratoma
Authors: Harkness Robert , Kelly Paul J. , McCluggage W. Glenn
Published: October 2019

Ovarian high-grade neuroendocrine carcinomas (NECs) (small cell and large cell NEC) are rare neoplasms. They may arise in association with other ovarian tumors, most commonly epithelial neoplasms and rarely teratomas. We report a case of an 19-yr-old female with bilateral ovarian teratomas with a high-grade NEC (immunohistochemically positive with chromogranin, synaptophysin, and CD56 and MIB1 proliferation index in excess of 90%) arising within one of these. Although CK20 was negative, the NEC exhibited an immunophenotype suggestive of a Merkel cell carcinoma with diffuse positive staining with FLI-1, SATB2 and neurofilament, markers which are preferentially expressed in Merkel cell carcinoma compared with other NECs. There was also diffuse staining for SALL4. Immunohistochemistry and molecular studies for Merkel cell polyomavirus were negative. Immunohistochemical staining for CK20, FLI-1, SATB2, neurofilament, and SALL4 was performed in 6 additional primary ovarian high-grade NECs; One, 5, 5, 1, and 0 cases were positive for CK20, FLI-1, SATB2, neurofilament, and SALL4, respectively, usually with very focal immunoreactivity. Pathologists should be aware of these potential unexpected staining patterns in ovarian NECs as positivity may result in consideration of other neoplasms.
Reevaluating the Current Model of Rhinoplasty Training and Future Directions: A Role for Focused, Maneuver-Specific Simulation
Authors: Zammit Dino , Ponnudurai Nirros , Safran Tyler , Gilardino Mirko
Published: October 2019

Background:

Rhinoplasty is known for its complexity in planning and execution. For trainees, knowledge acquisition is often adequately attained. The mastery of skills, however, occurs by means of hands-on exposure, which continues to be a challenge. This article discusses the positive progress made in rhinoplasty training, and objectively demonstrates a need for more hands-on rhinoplasty exposure for residents.

Methods:

A systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Concurrently, an online survey was developed, assessing resident comfort and training in rhinoplasty, and e-mailed to Canadian and U.S. plastic surgery training programs.

Results: One hundred thirty-eight

residents completed the survey, 62 junior (first- to third-year residents) and 76 senior residents (fourth- to sixth-year residents). Seventy-two percent of senior residents (95 percent of sixth-year residents) reported adequate rhinoplasty exposure, as opposed to 13 percent of junior residents. Seventy-five percent of senior residents most often participated as observers or first assistants, 25 percent participated as co-surgeons, and 73.9 percent did not perform a key rhinoplasty step more than five times. Residents felt the three most difficult steps of rhinoplasty were nasal osteotomy (76.1 percent), caudal septum/anterior nasal spine manipulation (65.2 percent), and nasal tip sutures (55.8 percent), and 73.9 percent felt that simulator training would substantially improve confidence.

Conclusions:

Despite sufficient exposure to rhinoplasties, residents were least confident in performing rhinoplasties relative to other aesthetic procedures, likely because of the high proportion of rhinoplasty exposure that is observational as opposed to hands-on acquisition of surgical maneuvers in the operating room. The survey established the maneuvers residents find the most difficult, and as programs adopt competency-based training, developing rhinoplasty simulators targeting specific identified steps may help improve competence for rhinoplasty skills.
A Matched-Pair Analysis of Prepectoral with Subpectoral Breast Reconstruction: Is There a Difference in Postoperative Complication Rate?
Authors: Momeni Arash , Remington Austin C. , Wan Derrick C. , Nguyen Dung , Gurtner Geoffrey C.
Published: October 2019

Background:

The development of acellular dermal matrices has revolutionized implant-based breast reconstruction. The most recent development has been the introduction of prepectoral breast reconstruction. However, concerns have been expressed related to the quality of soft-tissue coverage and infectious complications. Thus, the authors felt it prudent to perform a matched-pair analysis of clinical outcomes following prepectoral and subpectoral tissue expander placement.

Methods:

A retrospective study of patients who underwent immediate breast reconstruction by means of prepectoral (group 1) and dual-plane subpectoral (group 2) tissue expander placement was performed. Patients in each group were matched for age, body mass index, history of radiotherapy, and type of acellular dermal matrix. Of note, patients in group 1 received perioperative antibiotic prophylaxis for less than 24 hours, whereas patients in group 2 received antibiotic prophylaxis for at least 1 week.

Results:

A total of 80 patients (138 breast reconstructions) were included in the study (group 1, n = 40; group 2, n = 40). No difference in total postoperative complication rate (p = 0.356) and mastectomy skin necrosis rate (p = 1.0) was noted. Observed differences in major complications (p = 0.06), major infection (p = 0.09), and loss of reconstruction (p = 0.09) were not found to be significant.

Conclusion:

Immediate prepectoral tissue expander insertion with anterior acellular dermal matrix coverage and less than 24 hours of antibiotic prophylaxis is safe and compares favorably to subpectoral tissue expander placement with an inferior acellular dermal matrix sling and a prolonged course of antibiotics.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Intraoperative Surgical Navigation Reduces the Surgical Time Required to Treat Acute Major Facial Fractures
Authors: Bergeron Léonard , Bouchard Sandrine , Bonapace-Potvin Michelle , Bergeron François
Published: October 2019

Background:

Assessing bone reduction and implant placement in facial fractures is time-consuming because of limited visibility. An intraoperative navigation system allows real-time confirmation of bone positioning and implant placement on the patient’s computed tomographic scan. This circumvents the visibility problem and therefore appears to shorten the surgery time. The goal of this study was therefore to determine whether intraoperative navigation reduces the surgical time required to treat patients with acute major facial fractures.

Methods:

In this retrospective quasi-experimental study, 50 patients with major facial fractures were identified and randomly assigned to treatment groups. Twenty-two were treated without the use of a navigation system, and 28 were treated using navigation. The Facial frActure Severity Score (FASS) was devised to better assess and control for complexity of cases and control for possible selection bias.

Results:

The FASS was directly linked to surgery time, whether or not navigation was used. An analysis of covariance demonstrated that the surgical time required to treat major facial fractures, taking into account the FASS, was reduced by 36.1 percent (124.8 minutes) when navigation was used.

Conclusions:

This study compared the surgical time required to treat patients with major facial fractures, with and without a navigation system. The use of a navigation system reduced the surgical time by 36.1 percent. This is a significant improvement in reducing the length of craniomaxillofacial procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.