bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study
Authors: Jung Seulgi , Ye Byong Duk , Lee Ho-Su , Baek Jiwon , Kim Gyeonghoon , Park Dohoon , Park Sang Hyoung , Yang Suk-Kyun , Han Buhm , Liu Jianjun , Song Kyuyoung
Published: March 2021

Background and Aims

Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls.

Methods

An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls.

Results

The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [pcombined = 6.56 × 10–9] and two novel loci for Crohn’s disease [CD] at rs2240751 on 19p13 [pcombined = 3.03 × 10–8] and rs6936629 on 6q22 [pcombined = 3.63 × 10–8]. Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population.

Conclusions

The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.
Diversionary Politics and Territorial Disputes: Evidence from Turkish Airspace Incursions
Authors: Mehrl Marius , Choulis Ioannis
Published: March 2021

Diversionary theories of interstate conflict suggest that domestic problems push leaders to initiate hostilities against foreign foes in order to garner support. However, the empirical support for this proposition is mixed as critics point out that leaders should not start conflicts that can be extremely costly for them, potentially even removing them from office. We propose that while leaders may not initiate new conflicts, they do tap into existing territorial disputes when facing internal disapproval. That is, they engage in material acts of foreign policy showing domestic audiences that they defend or emphasize their country's claim while being unlikely to result in full-scale armed confrontations. To test this claim, we use monthly data, covering the period 2013–2020, on leader approval and incursions into contested airspace from Turkey's long-standing territorial dispute with Greece. Results from time-series models offer support for our expectation.
Geodynamic models of short-lived, long-lived and periodic flat slab subduction
Authors: Schellart W P , Strak V
Published: March 2021

Flat slab subduction has been ascribed to a variety of causes, including subduction of buoyant ridges/plateaus and forced trench retreat. The former, however, has irregular spatial correlations with flat slabs, while the latter has required external forcing in geodynamic subduction models, which might be insufficient or absent in nature. In this paper, we present buoyancy-driven numerical geodynamic models and aim to investigate flat slab subduction in the absence of external forcing as well as test the influence of overriding plate strength, subducting plate thickness, inclusion/exclusion of an oceanic plateau and lower mantle viscosity on flat slab formation and its evolution. Flat slab subduction is reproduced during normal oceanic subduction in the absence of ridge/plateau subduction and without externally forced plate motion. Subduction of a plateau-like feature, in this buoyancy-driven setting, enhances slab steepening. In models that produce flat slab subduction, it only commences after a prolonged period of slab dip angle reduction during lower mantle slab penetration. The flat slab is supported by mantle wedge suction, vertical compressive stresses at the base of the slab and upper mantle slab buckling stresses. Our models demonstrate three modes of flat slab subduction, namely short-lived (transient) flat slab subduction, long-lived flat slab subduction and periodic flat slab subduction, which occur for different model parameter combinations. Most models demonstrate slab folding at the 660 km discontinuity, which produces periodic changes in the upper mantle slab dip angle. With relatively high overriding plate strength or large subducting plate thickness, such folding results in periodic changes in the dip angle of the flat slab segment, which can lead to periodic flat slab subduction, providing a potential explanation for periodic arc migration. Flat slab subduction ends due to the local overriding plate shortening and thickening it produces, which forces mantle wedge opening and a reduction in mantle wedge suction. As overriding plate strength controls the shortening rate, it has a strong control on the duration of flat slab subduction, which increases with increasing strength. For the weakest overriding plate, flat slab subduction is short-lived and lasts only 6 Myr, while for the strongest overriding plate flat slab subduction is long-lived and exceeds 75 Myr. Progressive overriding plate shortening during flat slab subduction might explain why flat slab subduction terminated in the Eocene in western North America and in the Jurassic in South China.
Generation and characterization of a P2rx2 V60L mouse model for DFNA41
Authors: Chen Xiaoya , Abad Clemer , Chen Zheng-yi , Young Juan I , Gurumurthy Channabasavaiah B , Walz Katherina , Liu Xue Zhong
Published: March 2021

P2RX2 encodes the P2X2 receptor, which is an adenosine triphosphate (ATP) gated (purinoreceptor) ion channel. P2RX2 c. 178G > T (p.V60L) mutation was previously identified in two unrelated Chinese families, as the cause of human DFNA41, a form of dominant, early-onset and progressive sensorineural hearing loss. We generated and characterized a knock-in mouse model based on human p.V60L mutation that recapitulates the human phenotype. Heterozygous KI mice started to exhibit hearing loss at 21-day-old and progressed to deafness by 6-month-old. Vestibular dysfunction was also observed in mutant mice. Abnormal morphology of the inner hair cells and ribbon synapses was progressively observed in KI animals suggesting that P2rx2 plays a role in the membrane spatial location of the ribbon synapses. These results suggest that P2rx2 is essential for acoustic information transfer, which can be the molecular mechanism related to hearing loss.
Alternative data sources can fill the gaps in data-poor fisheries
Authors: Machado Alexandre M S , Giehl Eduardo L Hettwer , Fernandes Luiza Pacheco , Ingram Simon N , Daura-Jorge Fábio G
Published: March 2021

Assessing fish stocks harvested by small-scale fisheries is challenging. The lack of official fisheries data constrains the proper management of such fisheries. Thus, alternative sources of information are crucial to enrich data-poor fisheries. Here, we evaluated different sources of data for the mullet (Mugil liza) fishery, one of the most important but overexploited fisheries in Brazil. We gathered three alternative sources of catch data by artisanal fisheries: 14 years of self-reported catches by artisanal fishers across 24 municipalities; 16 years of catches by traditional beach seines mined from news outlets; and 13 years from a single community monitoring their beach seine catches. We tested whether alternative data sources follow the same trends of landing reports from systematic, official monitoring of the industrial fleet. We fitted Bayesian time-series models to test if environmental changes and stock abundance can predict these data. We found that only self-reported catches matched the official reporting trends, thereby improving our understanding of changes in the mullet stock. These findings reveal that self-reported catches by fishers provide reliable additional data useful for management. Self-reporting data are cost-effective, deals with the complexity of small-scale fisheries, and welcomes fishers as key stakeholders in management practices.
Educational intervention to improve the safety medication process: a review using the GRADE approach
Authors: Giannetta Noemi , Dionisi Sara , Tonello Monica , Cappadona Rosaria , Di Muzio Marco , Di Simone Emanuele
Published: March 2021

Objectives

Medication errors are frequent and affect patient safety in all the world. This review using the GRADE approach aims to identify the educational intervention which improves nursing medication competences and knowledge.

Methods

According to PRISMA statement, a review was conducted.

Key findings

In this review of nine studies, we determined that there is a lot of educational intervention aimed to improve nursing knowledge, such as traditional classroom training, simulation, e-learning, slide show presentations and the use of posters and pamphlets or mobile application. All of these can improve the medication process and nursing skills. Only three studies reached moderate, and two studies reached low-quality ratings.

Conclusions

Our findings show that all educational interventions can lead to medication without harm. This work will inform regulators, public health initiatives and policy makers considering the nursing educational intervention for increasing patient safety and improve medication competence and knowledge.
The influence of surface CO2 condensation on the evolution of warm and cold rocky planets orbiting Sun-like stars
Authors: Bonati I , Ramirez R M
Published: March 2021

The habitable zone is the region around a star where standing bodies of liquid water can be stable on a planetary surface. Its width is often assumed to be dictated by the efficiency of the carbonate–silicate cycle, which has maintained habitable surface conditions on our planet for billions of years. This cycle may be inhibited by surface condensation of significant amounts of CO2 ice, which is likely to occur on distant planets containing high enough levels of atmospheric CO2. Such a process could permanently trap CO2 ice within the planet, threatening its long-term habitability. Recent work has modelled this scenario for initially cold and icy planetary bodies orbiting the Sun. Here, we use an advanced energy balance model to consider both initially warm and cold rapidly rotating planets orbiting F - K stars. We show that the range of orbital distances where significant surface CO2 ice condensation occurs is significantly reduced for warm start planets. Star type does not affect this conclusion, although surface CO2 ice condenses over a larger fraction of the habitable zone around hotter stars. The warm start simulations are thus consistent with 1D model predictions, suggesting that the classical habitable zone limits in those earlier models are still valid. We also find that the cold start simulations exhibit trends that are consistent with those of previous work for the Sun although we now extend the analysis to other star types.
Kinetic powers of the relativistic jets in Mrk 421 and Mrk 501
Authors: Deng Xiao-Chun , Hu Wen , Lu Fang-Wu , Dai Ben-Zhong
Published: March 2021

Using the standard one-zone synchrotron self-Compton model and the Markov chain Monte Carlo (MCMC) technique, we systematically analyse the quasi-simultaneous multiwavelength spectral energy distributions (SEDs) of Mrk 421 and Mrk 501 during states of relatively low activity. With this model in place, a semi-analytical method is developed to examine the uncertainty in jet power estimation caused by degeneracy of the radiative models. The semi-analytical method, in combination with the MCMC technique, allows us to explore the jet properties over a wide range of the variability time-scale. Our results seem to support the following. (i) In both Mrk 421 and Mrk 501, the jets are powered by rapidly rotating black holes. The black hole spin in Mrk 501 could be lower than that in Mrk 421 or possibly they are equal under the assumption of the Blandford–Znajek mechanism. (ii) The energy losses, which could be used to form the large-scale radio structure, are important for reconciling the differences of the kinetic power derived from the observations of the large-scale structure and the SED fitting results. Moreover, the jet energy losses in the propagation are more significant for Mrk 501 than for Mrk 421.
The prospects for observing [O iii] 52 micron emission from galaxies during the Epoch of Reionization
Authors: Yang Shengqi , Lidz Adam , Popping Gergö
Published: March 2021

The [O iii] 88 $\mu$m fine-structure emission line has been detected into the Epoch of Reionization (EoR) from star-forming galaxies at redshifts 6 < z ≲ 9 with ALMA. These measurements provide valuable information regarding the properties of the interstellar medium (ISM) in the highest redshift galaxies discovered thus far. The [O iii] 88 $\mu$m line observations leave, however, a degeneracy between the gas density and metallicity in these systems. Here, we quantify the prospects for breaking this degeneracy using future ALMA observations of the [O iii] 52 $\mu$m line. Among the current set of 10 [O iii] 88 $\mu$m emitters at 6 < z ≲ 9, we forecast 52 $\mu$m detections (at 6σ) in SXDF-NB1006-2, B14-6566, J0217-0208, and J1211-0118 within on-source observing times of 2–10 h, provided their gas densities are larger than about nH ≳ 102–103 cm−3. Other targets generally require much longer integration times for a 6σ detection. Either successful detections of the 52 $\mu$m line or reliable upper limits will lead to significantly tighter constraints on ISM parameters. The forecasted improvements are as large as ∼3 dex in gas density and ∼1 dex in metallicity for some regions of parameter space. We suggest SXDF-NB1006-2 as a promising first target for 52 $\mu$m line measurements. We discuss how such measurements will help in understanding the mass–metallicity relationship during the EoR.
Gravitational lensing in LoTSS DR2: extremely faint 144-MHz radio emission from two highly magnified quasars
Authors: McKean J P , Luichies R , Drabent A , Gürkan G , Hartley P , Lafontaine A , Prandoni I , Röttgering H J A , Shimwell T W , Stacey H R , Tasse C
Published: March 2021

We report extremely faint 144 MHz radio emission from two gravitationally lensed quasars, SDSS J1004+4112 (z = 1.730) and SDSS J2222+2745 (z = 2.803), using the LOFAR Two Metre Sky Survey (LoTSS) data release 2. After correcting for the lensing magnifications, the two objects have intrinsic flux-densities of 13 ± 2 and 58 ± 6 μJy, respectively, corresponding to 144 MHz rest-frame luminosities of 1023.2 ± 0.2 and 1024.42 ± 0.05 W Hz−1, respectively. In the case of SDSS J1004+4112, the intrinsic flux density is close to the confusion limit of LoTSS, making this radio source the faintest to be detected thus far at low frequencies, and the lowest luminosity known at z ≳ 0.65. Under the assumption that all of the radio emission is due to star-formation processes, the quasar host galaxies are predicted to have star-formation rates of $5.5^{+1.8}_{-1.4}$ and $73^{+34}_{-22}$ M⊙ yr−1, respectively. Further multiwavelength observations at higher angular resolution will be needed to determine if any of the detected radio emission is due to weak jets associated with the quasars.
ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties
Authors: Xiong Guoli , Wu Zhenxing , Yi Jiacai , Fu Li , Yang Zhijiang , Hsieh Changyu , Yin Mingzhu , Zeng Xiangxiang , Wu Chengkun , Lu Aiping , Chen Xiang , Hou Tingjun , Cao Dongsheng
Published: March 2021

Because undesirable pharmacokinetics and toxicity of candidate compounds are the main reasons for the failure of drug development, it has been widely recognized that absorption, distribution, metabolism, excretion and toxicity (ADMET) should be evaluated as early as possible. In silico ADMET evaluation models have been developed as an additional tool to assist medicinal chemists in the design and optimization of leads. Here, we announced the release of ADMETlab 2.0, a completely redesigned version of the widely used AMDETlab web server for the predictions of pharmacokinetics and toxicity properties of chemicals, of which the supported ADMET-related endpoints are approximately twice the number of the endpoints in the previous version, including 17 physicochemical properties, 13 medicinal chemistry properties, 23 ADME properties, 27 toxicity endpoints and 8 toxicophore rules (751 substructures). A multi-task graph attention framework was employed to develop the robust and accurate models in ADMETlab 2.0. The batch computation module was provided in response to numerous requests from users, and the representation of the results was further optimized. The ADMETlab 2.0 server is freely available, without registration, at https://admetmesh.scbdd.com/.
Holographic entanglement entropy of a de Sitter braneworld with Lovelock terms
Authors: Kushihara Kouki , Izumi Keisuke , Shiromizu Tetsuya
Published: March 2021

We examine the de Sitter entropy in the braneworld model with the Gauss–Bonnet/Lovelock terms. We find that the de Sitter entropy computed through the Euclidean action exactly coincides with the holographic entanglement entropy.
Most Genomic Loci Misrepresent the Phylogeny of an Avian Radiation Because of Ancient Gene Flow
Authors: Zhang Dezhi , Rheindt Frank E , She Huishang , Cheng Yalin , Song Gang , Jia Chenxi , Qu Yanhua , Alström Per , Lei Fumin
Published: March 2021

Phylogenetic trees based on genome-wide sequence data may not always represent the true evolutionary history for a variety of reasons. One process that can lead to incorrect reconstruction of species phylogenies is gene flow, especially if interspecific gene flow has affected large parts of the genome. We investigated phylogenetic relationships within a clade comprising eight species of passerine birds (Phylloscopidae, Phylloscopus, leaf warblers) using one de novo genome assembly and 78 resequenced genomes. On the basis of hypothesis-exclusion trials based on D-statistics, phylogenetic network analysis, and demographic inference analysis, we identified ancient gene flow affecting large parts of the genome between one species and the ancestral lineage of a sister species pair. This ancient gene flow consistently caused erroneous reconstruction of the phylogeny when using large amounts of genome-wide sequence data. In contrast, the true relationships were captured when smaller parts of the genome were analyzed, showing that the “winner-takes-all democratic majority tree” is not necessarily the true species tree. Under this condition, smaller amounts of data may sometimes avoid the effects of gene flow due to stochastic sampling, as hidden reticulation histories are more likely to emerge from the use of larger data sets, especially whole-genome data sets. In addition, we also found that genomic regions affected by ancient gene flow generally exhibited higher genomic differentiation but a lower recombination rate and nucleotide diversity. Our study highlights the importance of considering reticulation in phylogenetic reconstructions in the genomic era.[Bifurcation; introgression; recombination; reticulation; Phylloscopus.]
Association of leptospirosis and scrub typhus in acute encephalitis syndrome in a tertiary care hospital in Odisha, India
Authors: Das Bidyut Kumar , Mohanty Sriprasad , Sahoo Prakash Kumar
Published: March 2021

Background

Acute encephalitis syndrome (AES) is a major public health concern in India, causing febrile illness principally associated with viral infection. Bacteria-like scrub typhus and leptospirosis also cause acute febrile illness. Therefore, this study was conceived to address the possible etiological agents contributing to sporadic AES in a tertiary care center in Odisha, India.

Method

This was a prospective hospital-based study that enrolled 92 consecutive patients with clinically diagnosed AES whose blood/cerebrospinal fluid samples were tested for IgM antibodies to dengue, Japanese encephalitis (JE), herpes simplex virus (HSV), Epstein-Barr virus (EBV), leptospirosis and scrub typhus.

Results

Viral antibodies to dengue were detected in three (3.26%) cases, HSV1 in four (4.34%) and HSV2 in three (3.26%) cases. Significantly, antibodies to EBV in 22 (23.591%) and to JE in 27 (29.34%) cases were detected. Notably, 30 (32.60%) and 11(12.0%) of patients had IgM antibodies to leptospirosis and scrub typhus, respectively.

Conclusion

This observation indicates an association of leptospirosis and scrub typhus infection in sporadic cases of AES, besides other viruses.
Parental Experiences of Infant Car Bed Use After Failure of Car Seat Tolerance Screen
Authors: O'Connor Christina M. , McGrath Jacqueline , DeGrazia Michele
Published: March 2021

Background:

Failure of the car seat tolerance screen (CSTS) during hospitalization often leads to a recommendation for automobile travel within a car bed at discharge.

Purpose:

To describe the parental experience utilizing a car bed for infant automobile transportation.

Methods:

A descriptive, qualitative study design was undertaken with a purposive sample of parents recruited for a single interview in the pulmonary clinic at the time of the follow-up CSTS, approximately 1 month after hospital discharge. Interviews, guided by a semistructured interview tool, provided a holistic understanding of the parental experience utilizing car bed travel.

Findings/Results:

Data from 15 parental interviews revealed an overarching emotional journey consisting of 5 themes: (1) an adjustment period; (2) decision-making related to the car bed purchase; (3) encounters with varied provider education and knowledge; (4) safety and security of the car bed during transit; and (5) space and mobility restrictions imposed by the car bed.

Implications for Practice

While recommendations exist for infant travel in a car seat, supportive recommendations for parents with an infant who needs to travel in a car bed do not exist. Based on study findings, providing parents supportive guidelines, education, and recommendations for their infant requiring travel in a car bed may be a strategy to ease the stress experienced in this situation.

Implications for Research:

Findings indicated a need to develop policies and standards, as well as comprehensive education, for providers and parents related to car bed travel. Further research is needed to identify strategies to best support parents and infants.
A Review of the NANN Research Summit Experience
Authors: Esser Media S. , Shelley Lauren , Moore Tiffany A.
Published: March 2021

Background:

The NANN Research Summit has been providing a platform for neonatal scholarship and clinical inquiry for 15 years. As the discipline of nursing and nursing research continue to evolve, it is important to gain perspective on current trends and needs for areas of strength and growth.

Purpose:

To evaluate participant outcomes of the NANN Research Summit and determine opportunities for improvement.

Methods:

A 9-question survey was sent to 90 past participants for the Research Summit years 2015-2019.

Results:

Thirty-seven (41%) participants from 2015 to 2019 responded. Of those responding, 75% continued to pursue their presentation topic; 95% felt empowered to continue their research based on their Summit experience; 84% felt more comfortable presenting their research findings after attending; 84% felt confident in publishing research after attending the Summit, with 43% reporting publications. These accomplished results would not have been possible without Mead Johnson's support. In addition, 57% did not publish the work presented and 65% lacked continued mentorship.

Implications for Practice:

A redesigned Summit is presented to address the priorities for growth and alignment with continued emphasis on collegiality among neonatal nurse scholars. The redesigned Summit will promote continued clinical inquiry as a result of intentional focus on mentorship and development of scholarship.

Implications for Research:

The data collected from this initial survey will continue to serve as the basis for future data collection. Continued evaluation of strengths and areas for growth including the number of publications and mentorship experience can lead to expansion of research for the Summit facilitators and participants.
Reducing Admission Hypothermia in Neonates Born at Less Than 32 Weeks or 1500 g
Authors: Frazer Milena , Ciarlo Amy , Hinderer Katherine A. , Briere Carrie-Ellen
Published: March 2021

Purpose:

The purpose of this quality improvement project was to decrease admission hypothermia in neonates born at less than 32 weeks or less than 1500 g.

Methods:

At delivery, neonates born less than 1500 g or at less than 32 weeks received polyurethane bags, polyurethane hats, and chemical mattresses. New practice guidelines from 2016 promoted this practice for all neonates born at less than 32 weeks, but the authors' prior work indicated that all neonates born less than 1500 g were at risk (regardless of gestational age) and would benefit from these interventions.

Findings/Results:

After the intervention, only 2.1% (n = 2) of neonates born less than 1500 g or at less than 32 weeks were admitted moderately hypothermic (<36°C) compared with 9.6% in 2016, 20.2% in 2015, and 32.4% in 2014. Overall, the mean admission temperature in 2017 was 37°C, improved from 36.6°C in 2016, 36.3°C in 2015, and 36.2°C in 2014 (P < .001).

Implications for Practice:

The intervention significantly reduced the number of neonates admitted moderately hypothermic (<36.0°C) to this neonatal intensive care unit. Using chemical mattresses and polyurethane bags with neonates born less than 1500 g or at less than 32 weeks (compared with only <1000 g) improved admission temperatures. It is important to include all neonates born less than 1500 g in these practice interventions and not only those born at less than 32 weeks; both gestational age and weight should guide practice.

Implications for Research:

More research is needed on the effects of thermoregulation interventions and hyperthermia in neonates, as well as best practice thermoregulation interventions for preterm and ill neonates of all gestational ages and weights.
Limb Lengthening for Congenital Deficiencies Using External Fixation Combined With Flexible Intramedullary Nailing: A Multicenter Study
Authors: Popkov Arnold , Pietrzak Szymon , Antonov Alexander , Parol Tomasz , Lazović Mikan , Podeszwa David , Popkov Dmitry
Published: March 2021

Background:

Hydroxyapatite (HA) coated flexible intramedullary nailing (FIN) stimulates osteogenic activity. The role of HA-coated intramedullary nails remains unclear in normal bone lengthening. The goal of this study was to quantify the influence of FIN on the External Fixation Index (EFI) in patients with congenital lower limb discrepancy.

Methods:

Patients with femoral deficiency and fibular hemimelia underwent lengthening by the combined technique of external fixation with titanium (Ti) FIN or HA coated FIN and returned for follow-up at least 12 months after frame removal.

Results:

Seventy patients (mean age of 12.6 y) were included: 19 monofocal femoral lengthenings, 35 tibial monofocal lengthenings, 16 tibial bifocal lengthenings. The mean EFI’s for those treated with and without HA-coated nails were not significantly different. The Conover posthoc analysis did not reveal a significant influence of the type of FIN on EFI in any subgroup. However, 2-way analysis of variance revealed simultaneous effects of nail types and age on the EFI in tibial bifocal lengthening.

Significant positive correlation between the ratio “nail diameter/medullary shaft diameter” and EFI in tibial bifocal non–HA-coated FIN lengthening, and a significant positive correlation between age and EFI for femoral non–HA-coated FIN lengthening, tibial monofocal and bifocal HA-coated FIN lengthening were revealed.

There were 4 cases of fracture at lengthening site required unscheduled surgery. In the non–HA-coated group, there was a statistically significant negative correlation between nail diameter and fracture occurrence at the lengthening site after frame removal. A ratio of <0.15 likely does not ensure required mechanical stability and support.

Conclusions:

Both Ti-nail and HA-coated nail lengthening provide good and excellent outcomes for femoral and tibial monosegmental lengthening procedures and ensure reduced EFI. In congenital disorders which were not associated with abnormal bone, there are no differences with regard to EFI using HA-coated or non–HA-coated FIN. The ratio of “elastic Ti-nail diameter/medullary canal diameter at narrowest site” <0.15 seems to be associated with higher risk of fracture at the lengthening site after frame removal.
Early Opioid Consumption Patterns After Anterior Cervical Spine Surgery
Authors: Lovecchio Francis , Premkumar Ajay , Steinhaus Michael , Alexander Koo , Mejia Dianna , Yoo Joon S. , Lafage Virginie , Iyer Sravisht , Huang Russel , Lebl Darren , Qureshi Sheeraz , Kim Han Jo , Singh Kern , Albert Todd
Published: March 2021

Study Design:

This is a prospective observational study.

Objective:

The aim was to record daily opioid use and pain levels after 1-level or 2-level anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA).

Summary of Background Data:

Data to inform opioid prescription guidelines following ACDF or CDA is lacking. Understanding postoperative opioid consumption behaviors is critical to provide appropriate postdischarge prescriptions.

Methods:

Patients undergoing 1-level or 2-level primary ACDF or CDA were consecutively enrolled at 2 participating institutions between March 2018 and March 2019. Patients with opioid dependence (defined as daily use ≥6 mo before surgery) were excluded. Starting postoperative day 1, daily opioid use and numeric pain rating scale pain levels were collected through a Health Insurance Portability and Accountability Act-compliant, automated text-messaging system. To facilitate clinical applications, opioid use was converted from oral morphine equivalents into “pills” (oxycodone 5 mg equivalents). After 6 weeks or upon patient-reported cessation of opioid use, final survey questions were asked. Refill data were verified from the state prescription registry. Risk factors for patients in top quartile of consumption were analyzed.

Results:

Of 57 patients, 48 completed the daily queries (84.2%). Mean age of the patient sample was 50.2±10.9 years. Thirty-two patients (66.7%) underwent ACDF and 16 CDA (33.3%); 64.6% one level; 35.4% two levels. Median postdischarge use was 6.7 pills (range: 0–160). Cumulative opioid use did not vary between the 1-level and 2-level groups (median pill consumption, 10 interquartile range: 1.3–31.3 vs. 4 interquartile range: 0–18, respectively, P=0.085). Thirteen patients (27.1%) did not use any opioids after discharge. Of those patients that took opioids after discharge, half ceased opioids by postoperative day 8. Preoperative intermittent opioid use was associated with the top quartile of opioid consumption (9.1% vs. 50%, P=0.006).

Conclusion:

Given that most patients use few opioids, patients could be offered the option of a 12 oxycodone 5 mg (90 oral morphine equivalents) discharge prescription, accompanied by education on appropriate opioid use and disposal.
Systemic treatment of metastatic squamous cell carcinoma of the head and neck: proposal for management changes
Authors: Peyrade Frédéric , Borel Christian , Daste Amaury , Even Carolie , Saada-Bouzid Esma , Guigay Joël
Published: March 2021

Purpose of review

Worldwide, head and neck carcinomas account for 5% of all malignancies. Two-thirds of patients relapse after initial multimodal therapy. Until early 2010, the median overall survival (OS) of metastatic patients was about 10 months.

Recent findings

New drugs have been incorporated in patient management, thus enabling an increase in OS. Several first and second line protocols are now available but the lack of direct comparison makes the choice difficult between them.

This work aims to define the comprehensive medical management of patients with relapsing head and neck carcinoma. In September 2020, the French head and neck groups GORTEC, Unicancer head and Neck group, GROCC and GETTEC decided to promote a one-day meeting to propose how to incorporate these new regimens in first and second line treatment for recurrent and metastatic head and neck cancer (R/M SCCHNC). Twelve French medical oncologist involved in the management of R/M SCCHNC for more than 10 years examined the literature and proposed a simple and practical management based on five criteria: age, delay from last platinum injection, combined positive score expression level, FIT or UNFIT patient according to physician decision, fast response needed or not.
Adverse effects from selected antidotes commonly used in poisonings
Authors: Hoegberg Lotte C.G. , Boegevig Soeren
Published: March 2021

The number of specific antidotes available is low compared to the wide range of substances, of natural or synthetic origin, able to produce toxic symptoms in the human body. Some of these antidotes being very specific in target and effect, e.g., antagonism at the μ-opioid receptors by naloxone in an opioid overdose, other antidotes being unspecific, e.g., glucagon or atropine in the case of betablocker poisoning or activated charcoal with its ability reduce absorption of a wide range of toxic substances. In the following, we present four important antidotes (N-acetylcysteine, deferoxamine, methylene blue and physostigmine) and focus on some of their reported potentially severe adverse effects.
Effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women: a systematic review and meta-analysis of randomized controlled trials
Authors: Yi Mingyu , Wang Sixue , Wu Ting , Zhang Xinyue , Jiang Li , Fang Xiaoling
Published: March 2021

Importance:

Because of the bothersome symptoms during women's menopausal period and the severe side effects of hormone therapy, it is meaningful to find new breakthroughs in improving menopausal women's quality of life.

Objective:

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating melatonin intake on the improvement of sleep quality, general menopausal symptom, mood states, as well as interaction of estradiol levels and body mass index (BMI) in menopausal women.

Evidence Review:

We used the search terms “melatonin” together with “menopause” or “post-menopause” or “peri-menopause” in multiple databases online including PubMed, Web of Science, Embase, Clinical trial, Cochrane Library, and China National Knowledge Infrastructure from the first publication year to October 2020. Interesting data included characteristics of the study design, study participants, intervention, and outcome measures. Risk of biases in RCTs was evaluated with the Cochrane tool. Fixed-effect models and random-effect models were used for meta-analysis according to heterogeneity. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in our study.

Findings:

Eight cohorts (n = 812) evaluating the effects of melatonin in menopausal women were included. Melatonin was used in every study with differences existing in dose (1 mg - 5 mg) and duration (3 to 12 mo). Improved physical symptoms (standard mean difference [SMD] −0.376; 95% CI, −0.599 to −0.153, P = 0.001) merged in four RCTs. Melatonin treatment resulted in no benefits to sleep quality (SMD −0.659; 95% CI, −1.535 to 0.217, P = 0.141) and general menopause symptoms (SMD −0.625; 95% CI, −1.354 to 0.105, P = 0.093) in four and three RCTs, respectively. More specifically, melatonin did not solve the psychological (SMD −0.026; 95% CI, −0.372 to 0.321, P = 0.884, I

2
 = 70.3%), sexual (SMD −0.661; 95% CI, −1.416 to 0.093, P = 0.086) and vasomotor (SMD −0.256; 95% CI, −0.701 to 0.188, P = 0.258) issues. No significant changes were observed in anxiety (SMD 0.018; 95% CI, −0.519 to 0.556, P = 0.946), depression (SMD 0.133; 95% CI, −0.435 to 0.702, P = 0.646), BMI (weighted mean difference 0.029 kg/m2; 95% CI, −0.183 to 0.240, P = 0.790) or estradiol levels (weighted mean difference 0.016 pg/mL; 95% CI, −1.220 to 1.252, P = 0.980).

Conclusions:

Melatonin seems to improve physical symptoms in menopausal women, but the general menopausal symptoms, sleep quality, mood state, estradiol levels, and BMI did not improve under melatonin intervention. However, multiple large-scale clinical randomized trials are needed to validate our conclusions.
Salvaging the Unsalvageable: Negative Pressure Wound Therapy for Severe Infection of Prosthetic Breast Reconstruction
Authors: Meybodi Farid , Sedaghat Negin , Elder Elisabeth , French James , Adams Kristian , Hsu Jeremy , Kanesalingam Kavitha , Brennan Meagan
Published: March 2021

Background:

Severe infections of implant-based breast reconstruction are challenging to treat. Traditional management is removal of the implant with a further attempt at reconstruction months later once the infection has settled. This study evaluates an alternative management protocol using negative pressure wound therapy with instillation (NPWTi).

Methods:

Consecutive patients with severe peri-prosthetic infection following breast reconstruction were managed using the Implant Salvage Protocol: removal of the prosthesis with application of a NPWTi dressing, changed every 3 days until a negative culture was obtained. A new prosthesis was then placed in the pocket. Data were collected on patient demographics, microbiological, hospital/operative information, and overall success of salvage. Descriptive statistics were used for analysis.

Results:

In total, 30 breast prostheses in 28 patients were treated for severe peri-prosthetic infection. Twenty-five (83%) implants were salvaged. Mean time from initial reconstruction surgery to presentation was 49.5 days (median 23, range 7–420). Mean hospital stay was 11.5 days (median 12.0, range 6–22), mean number of returns to the operating theater was 3.7 (median 3.0, range 2–7), and mean number of days to negative culture was 5.2 (median 4.0, range 1–14). The most common organisms were methicillin-sensitive Staphylococcus aureus (n = 9) and Serratia marcescens (n = 4). Most had a tissue expander (n = 24, 80%) or implant (n = 5, 16.7%) placed at the completion of therapy. There was no record of capsular contracture nor recurrent infection during follow-up (mean 39.4 months, range 6–74 months).

Conclusion:

An estimated 83% of prosthetic breast reconstructions with severe infection were successfully salvaged using NPWTi.
Relationship of Body Mass Index With Fuchs Endothelial Corneal Dystrophy Severity and TCF4 CTG18.1 Trinucleotide Repeat Expansion
Authors: Kinariwala Bhumi B. , Xu Timothy T. , Baratz Keith H. , Aleff Ross A. , Patel Sanjay V. , Maguire Leo J. , Fautsch Michael P. , Wieben Eric D. , Millen Amy E. , Patel Sangita P.
Published: March 2021

Purpose:

To investigate the association of body mass index (BMI) with Fuchs endothelial corneal dystrophy (FECD) severity and TCF4 CTG18.1 expansion.

Methods:

A total of 343 patients with FECD were enrolled from the Mayo Clinic. FECD severity was graded by slit-lamp biomicroscopy. BMI values were obtained from the electronic medical records. DNA extracted from leukocytes was analyzed for CTG18.1 expansion length, with ≥40 repeats considered expanded. Wilcoxon signed-rank tests were used to compare FECD grade and CTG18.1 expansion length in patients by BMI (<25, ≥25 to <30, and ≥30 kg/m2). FECD grade was regressed on age, sex, BMI, and CTG18.1 expansion and, separately, BMI on CTG18.1 expansion. Models were investigated for effect modification by age and sex with an interaction term of P < 0.05 considered statistically significant.

Results:

When examining the association between BMI and FECD, there was a significant interaction between BMI and sex (P for interaction = 0.004). When controlling for age and CTG18.1 expansion, a positive association was observed between BMI and FECD grade in women, but not in men. In addition, BMI was not associated with CTG18.1 expansion when controlling for age and sex.

Conclusions:

BMI was positively associated with FECD severity among women but not men. There was no significant association between BMI and CTG18.1 expansion. These findings suggest that increased BMI is potentially a modifiable risk factor for FECD disease progression among women.
Patient satisfaction with dabigatrean and warfarin for stroke prevention in atrial fibrillation: Taiwan PASSION study
Authors: Lee Chun-Wei , Liu Ming-En , Lee Tsung-Ming , Chang Rei-Yeuh , Huang Chun-Yao , Hu Yu-Feng , Yeh Hung-I
Published: March 2021

Background:

Patient satisfaction with oral anticoagulant (OAC) therapy is an important metric of care quality and has been associated with higher medication persistence. Among OACs, dabigatran has been shown to be non-inferior to vitamin K antagonists (VKAs) with increased ease of use for stroke prevention in patients with atrial fibrillation (AF). In this study, we sought to evaluate the expectations, convenience, and satisfaction of Taiwanese AF patients on dabigatran and VKA therapies as well as associated clinical outcomes.

Methods:

Patients with AF (paroxysmal, persistent, or permanent) receiving OAC medication from outpatient facilities were enrolled in 24 hospitals across Taiwan. Cohort A consisted of 139 patients switched from VKA to dabigatran, while cohort B was comprised of 1113 patients on newly initiated OAC therapy (VKA, 54). The Perception of Anticoagulant Treatment Questionnaire was distributed, and responses on a five-point Likert scale were aggregated and analyzed across demographic groups.

Results:

In cohort A, convenience and satisfaction scores continued to increase at follow-up and significantly higher, compared to baseline, but both treatments scored similarly in cohort B. In cohort B, the two highest expectation scores were that the OAC would be “easy to take” and could be “taken independently.” On the other hand, the patients were relatively less concerned about the side effects and cost of therapy before taking the OAC. For dabigatran-receiving patients, there were 1.1 stroke-related events per 100 patient-years and 3.0 bleeding-related events per 100 patient-years.

Conclusion:

In Taiwanese patients with AF and initially treated with VKA, switched to dabigatran resulted in higher convenience and treatment satisfaction. For those patients on newly initiated OAC treatment, VKA and dabigatran convenience and satisfaction scores were similar.
Predictors of delayed extubation following lung resection: Focusing on preoperative pulmonary function and incentive spirometry
Authors: Ko Hsin-Kuo , Liu Ching-Yi , Ho Li-Ing , Chen Pei-Ku , Shie Huei-Guan
Published: March 2021

Background:

Delayed extubation is one of postoperative pulmonary complications (PPCs). Preoperative pulmonary function test (PFT) is an important assessment for patients undergoing lung resection. Volume-oriented incentive spirometry (IS) is one of physiotherapies to prevent PPCs. Preoperative PFT and IS volume (IS-v) can reflect the physiologic conditions of respiratory system in patients planning to undergo lung resection. However, the relationship between preoperative PFT/IS-v and delayed extubation in patients undergoing lung resection remains unclear. The study investigated the risk factors and impact of delayed extubation after lung resection. We aimed to achieve early recognition of patients being at a higher risk for developing postoperative delayed extubation after lung resection.

Methods:

This retrospective observational 4-year cohort study was conducted in a medical center, Taiwan. A total of 353 enrolled patients receiving thoracic surgery for lung resection were further categorized into the delayed extubation (n = 142, 40%) and non-delayed extubation (n = 211, 60%) groups.

Results:

In multivariate logistic regression analyses, age >65 years (adjusted odds ratio [AOR]: 2.60; 95% confidence interval [CI], 1.52-4.45), American Society of Anesthesiologists score >2 (AOR: 1.72; 95% CI, 1.05-2.82), anesthesia time >6hrs (AOR: 1.80; 95% CI, 1.13-2.88), pneumonectomy (AOR: 5.58; 95% CI, 1.62-19.19), and IS-v/inspiratory capacity (IC) ratio (AOR: 2.07; 95% CI, 1.16-3.68) were associated with delayed extubation after lung resection (all p < 0.05). Patients with delayed extubation were significantly associated with a higher proportion of other pulmonary complications, reintubation, mortality, and prolonged intensive care unit and hospital stays.

Conclusion:

Older age, poor general health status, longer anesthesia time, pneumonectomy, and IS-v/IC ratio could be the independent factors predictive for delayed extubation after lung resection, which was in turn associated with worse outcomes. Preoperative PFT and IS-v were valuable for early recognition of patients being at a higher risk for developing postoperative delayed extubation after lung resection.
Monitoring Enables Progress
Authors: Yogev Dotan , Shosberger Adi , Nehemia Chen , Harel Sasha , Yerushalmy‐Feler Anat , Ledder Oren , Orlanski‐Meyer Esther , Assa Amit , Slae Mordechai , Kori Michal , Elenberg Yigal , Shaoul Ron , Zifman Eyal , Shamaly Hussein , Berkowitz Drora , Sarit Peleg , Yerushalmi Baruch , Broide Efrat , On Avi , Elkayam Orit , Bayan Hino , Gorodnichenko Anna , Pinsk Vered , Shouval Dror S. , Turner Dan
Published: March 2021

Objectives:

In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation‐wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country.

Methods:

Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2–18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann‐Kendall test, reporting τ (tau) values.

Results:

The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ± 3.1 years, median disease duration 1.8 years (interquartile range 0.69–4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti‐tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 μg/mg (τ = 0.35; P = 0.015), and “resolution of inflammation” defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = −0.47; P = 0.001).

Conclusions:

Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.