bluuebunny/crossref_metadata_2025 huggingface dataset:
Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments
Authors: Cohen Alexander Li
Published: March 2022

A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders.

With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for “bedside-to bedside-translation” with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods.

Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy.
Correspondence of uroflowmetry and voiding diary in evaluation of voiding volume in children with lower urinary tract dysfunction
Authors: Özçift Burak
Published: March 2022

Background

Objective assessment of voided volumes in children with lower urinary tract dysfunction is important. This study aimed to compare and evaluate voided volumes obtained from a 48-h voiding diary and uroflowmetry in children with lower urinary tract dysfunction.

Methods

In this retrospective cohort study, voided volumes obtained by 48-h voiding diary and contemporaneous uroflowmetry were compared in terms of age, sex, and the three most common subtypes of lower urinary tract dysfunction (monosymptomatic nocturnal enuresis, overactive bladder, and dysfunctional voiding) in children. Patients were stratified according to voided volume differences between uroflowmetry and 48-h voiding diary.

Results

A total of 242 children were included in the study. Maximum and average voided volumes in uroflowmetry were higher than those in 48-h voiding diaries in the entire population (P < 0.001). While there was a significant difference between maximum voided volume in the two methods when evaluating patients with overactive bladder and dysfunctional voiding, there was no significant difference in those with monosymptomatic nocturnal enuresis (P = 0.001, P = 0.030, P = 0.206, respectively). A significant difference was observed between the three subtypes of lower urinary tract dysfunction in voided volumes (P < 0.001). When maximum and average voided volumes were compared for age subgroups, there was no significant difference in maximum and mean voided volumes only in voiding diary measurements (P > 0.05). When the two methods were compared, there was a difference in maximum and average voided volumes of more than 30% of the estimated bladder capacity in 94 (38.9%) and 86 (34.3%) children, respectively.

Conclusions

Uroflowmetry and a 48-h voiding diary should not be used interchangeably when evaluating children with lower urinary tract dysfunction. The results of uroflowmetry measurements should be used to support the diagnosis of underlying lower urinary tract dysfunction.
Comment on Environmental quality standards for diclofenac derived under the European Water Framework Directive: 1. Aquatic organisms (Leverett et al. in Environmental Sciences Europe 2021; 33: 133)
Authors: Maack Gerd , Äystö Lauri , Carere Mario , Clausen Henning , James Alice , Junghans Marion , Junttila Ville , Hollender Juliane , Marinov Dimitar , Stroomberg Gerard , Triebskorn Rita , Verbruggen Eric , Lettieri Teresa
Published: March 2022

Leverett et al. commented on the Environmental quality standard (EQS) for diclofenac derived under the European Water Framework Directive (Leverett et al. Environ Sci Eur 33: 133, 2021 https://doi.org/10.1186/s12302-021-00574-z). They postulated that the derived EQS value for diclofenac is not conducted according to the EQS Technical Guidance but rather using data of poor quality and relevance. Consequently, the authors suggested to use their alternative derived value instead. It is to be noted that the process for the EQS derivation for diclofenac is still ongoing and not finalized, and that as a consequence, any critical analysis is very premature. In general, within the current European Commission process, EQS value proposals are derived by expert groups led by the Joint Research Centre. In the specific case for diclofenac, Leverett and co-authors have also been actively involved as experts. This response to Leverett et al. (Environ Sci Eur 33:133, 2021) aims to clarify the reasoning-behind the proposal from a scientific point of view.
Phylogenetic relationships and evolutionary patterns of the genus Psammolestes Bergroth, 1911 (Hemiptera: Reduviidae: Triatominae)
Authors: Hernández Carolina , Alvarado Mateo , Salgado-Roa Fabian C. , Ballesteros Nathalia , Rueda-M Nicol , Oliveira Jader , Alevi Kaio Cesar Chaboli , da Rosa Joao Aristeu , Urbano Plutarco , Salazar Camilo , Ramírez Juan David
Published: March 2022

Background

The evolutionary history of biodiversity in South America has been poorly studied in the seasonal dry tropical forest (SDTF). Species diversification in this ecosystem may have a twofold explanation. First, intermittent connections in the middle and late Pleistocene promoted species dispersal and/or genetic connectivity between lineages isolated in disjunct patches of forest. Second, allopatric speciation proceeded immediately after the formation and colonization of the SDTF in the Neogene. Here we studied the diversification of Psammolestes, a genus endemic of the SDTF and naturally infected with Trypanosoma cruzi (agent of Chagas disease), using a combination of phylogenetic, population genetics and niche model methods, and evaluated the reliability of the three morphospecies currently recognized.

Results

Our multilocus analyses recovered P. coreodes and P. tertius in a monophyletic clade sister to P. arthuri. Species delimitation tests recovered these lineages as different species despite the shared genetic variation observed between P. coreodes and P. tertius in five genes. Also, genetic variation of the genus clustered in three groups that were consistent with the three morphospecies. Our demographic model predicted a scenario of divergence in absence of gene flow, suggesting that mixed haplotypes may be the result of shared ancestral variation since the divergence of the subtropical-temperate species P. coreodes and P. tertius. In contrast, the tropical species P. arthuri was highly differentiated from the other two in all tests of genetic structure, and consistently, the Monmonier’s algorithm identified a clear geographical barrier that separates this species from P. coreodes and P. tertius.

Conclusions

We found three genetically structured lineages within Psammolestes that diverged in absence of gene flow in the late Miocene. This result supports a scenario of species formation driven by geographical isolation rather than by divergence in the face of gene flow associated with climatic oscillations in the Pleistocene. Also, we identified the Amazon basin as a climatic barrier that separates tropical from subtropical-temperate species, thus promoting allopatric speciation after long range dispersion. Finally, each species of Psammolestes occupies different climatic niches suggesting that niche conservatism is not crucial for species differentiation. These findings influence the current vector surveillance programs of Chagas disease in the region.
The expanded inhibitor of apoptosis gene family in oysters possesses novel domain architectures and may play diverse roles in apoptosis following immune challenge
Authors: Witkop Erin M. , Proestou Dina A. , Gomez-Chiarri Marta
Published: March 2022

Background

Apoptosis plays important roles in a variety of functions, including immunity and response to environmental stress. The Inhibitor of Apoptosis (IAP) gene family of apoptosis regulators is expanded in molluscs, including eastern, Crassostrea virginica, and Pacific, Crassostrea gigas, oysters. The functional importance of IAP expansion in apoptosis and immunity in oysters remains unknown.

Results

Phylogenetic analysis of IAP genes in 10 molluscs identified lineage specific gene expansion in bivalve species. Greater IAP gene family expansion was observed in C. virginica than C. gigas (69 vs. 40), resulting mainly from tandem duplications. Functional domain analysis of oyster IAP proteins revealed 3 novel Baculoviral IAP Repeat (BIR) domain types and 14 domain architecture types across gene clusters, 4 of which are not present in model organisms. Phylogenetic analysis of bivalve IAPs suggests a complex history of domain loss and gain. Most IAP genes in oysters (76% of C. virginica and 82% of C. gigas), representing all domain architecture types, were expressed in response to immune challenge (Ostreid Herpesvirus OsHV-1, bacterial probionts Phaeobacter inhibens and Bacillus pumilus, several Vibrio spp., pathogenic Aliiroseovarius crassostreae, and protozoan parasite Perkinsus marinus). Patterns of IAP and apoptosis-related differential gene expression differed between the two oyster species, where C. virginica, in general, differentially expressed a unique set of IAP genes in each challenge, while C. gigas differentially expressed an overlapping set of IAP genes across challenges. Apoptosis gene expression patterns clustered mainly by resistance/susceptibility of the oyster host to immune challenge. Weighted Gene Correlation Network Analysis (WGCNA) revealed unique combinations of transcripts for 1 to 12 IAP domain architecture types, including novel types, were significantly co-expressed in response to immune challenge with transcripts in apoptosis-related pathways.

Conclusions

Unprecedented diversity characterized by novel BIR domains and protein domain architectures was observed in oyster IAPs. Complex patterns of gene expression of novel and conserved IAPs in response to a variety of ecologically-relevant immune challenges, combined with evidence of direct co-expression of IAP genes with apoptosis-related transcripts, suggests IAP expansion facilitates complex and nuanced regulation of apoptosis and other immune responses in oysters.
Improvement of prediction ability by integrating multi-omic datasets in barley
Authors: Wu Po-Ya , Stich Benjamin , Weisweiler Marius , Shrestha Asis , Erban Alexander , Westhoff Philipp , Inghelandt Delphine Van
Published: March 2022

Background

Genomic prediction (GP) based on single nucleotide polymorphisms (SNP) has become a broadly used tool to increase the gain of selection in plant breeding. However, using predictors that are biologically closer to the phenotypes such as transcriptome and metabolome may increase the prediction ability in GP. The objectives of this study were to (i) assess the prediction ability for three yield-related phenotypic traits using different omic datasets as single predictors compared to a SNP array, where these omic datasets included different types of sequence variants (full-SV, deleterious-dSV, and tolerant-tSV), different types of transcriptome (expression presence/absence variation-ePAV, gene expression-GE, and transcript expression-TE) sampled from two tissues, leaf and seedling, and metabolites (M); (ii) investigate the improvement in prediction ability when combining multiple omic datasets information to predict phenotypic variation in barley breeding programs; (iii) explore the predictive performance when using SV, GE, and ePAV from simulated 3’end mRNA sequencing of different lengths as predictors.

Results

The prediction ability from genomic best linear unbiased prediction (GBLUP) for the three traits using dSV information was higher than when using tSV, all SV information, or the SNP array. Any predictors from the transcriptome (GE, TE, as well as ePAV) and metabolome provided higher prediction abilities compared to the SNP array and SV on average across the three traits. In addition, some (di)-similarity existed between different omic datasets, and therefore provided complementary biological perspectives to phenotypic variation. Optimal combining the information of dSV, TE, ePAV, as well as metabolites into GP models could improve the prediction ability over that of the single predictors alone.

Conclusions

The use of integrated omic datasets in GP model is highly recommended. Furthermore, we evaluated a cost-effective approach generating 3’end mRNA sequencing with transcriptome data extracted from seedling without losing prediction ability in comparison to the full-length mRNA sequencing, paving the path for the use of such prediction methods in commercial breeding programs.
SprayNPray: user-friendly taxonomic profiling of genome and metagenome contigs
Authors: Garber Arkadiy I. , Armbruster Catherine R. , Lee Stella E. , Cooper Vaughn S. , Bomberger Jennifer M. , McAllister Sean M.
Published: March 2022

Background

Shotgun sequencing of cultured microbial isolates/individual eukaryotes (whole-genome sequencing) and microbial communities (metagenomics) has become commonplace in biology. Very often, sequenced samples encompass organisms spanning multiple domains of life, necessitating increasingly elaborate software for accurate taxonomic classification of assembled sequences.

Results

While many software tools for taxonomic classification exist, SprayNPray offers a quick and user-friendly, semi-automated approach, allowing users to separate contigs by taxonomy (and other metrics) of interest. Easy installation, usage, and intuitive output, which is amenable to visual inspection and/or further computational parsing, will reduce barriers for biologists beginning to analyze genomes and metagenomes. This approach can be used for broad-level overviews, preliminary analyses, or as a supplement to other taxonomic classification or binning software. SprayNPray profiles contigs using multiple metrics, including closest homologs from a user-specified reference database, gene density, read coverage, GC content, tetranucleotide frequency, and codon-usage bias.

Conclusions

The output from this software is designed to allow users to spot-check metagenome-assembled genomes, identify, and remove contigs from putative contaminants in isolate assemblies, identify bacteria in eukaryotic assemblies (and vice-versa), and identify possible horizontal gene transfer events.
A near-chromosome level genome assembly of the European hoverfly, Sphaerophoria rueppellii (Diptera: Syrphidae), provides comparative insights into insecticide resistance-related gene family evolution
Authors: Bailey Emma , Field Linda , Rawlings Christopher , King Rob , Mohareb Fady , Pak Keywan-Hassani , Hughes David , Williamson Martin , Ganko Eric , Buer Benjamin , Nauen Ralf
Published: March 2022

Background

Sphaerophoria rueppellii, a European species of hoverfly, is a highly effective beneficial predator of hemipteran crop pests including aphids, thrips and coleopteran/lepidopteran larvae in integrated pest management (IPM) programmes. It is also a key pollinator of a wide variety of important agricultural crops. No genomic information is currently available for S. rueppellii. Without genomic information for such beneficial predator species, we are unable to perform comparative analyses of insecticide target-sites and genes encoding metabolic enzymes potentially responsible for insecticide resistance, between crop pests and their predators. These metabolic mechanisms include several gene families - cytochrome P450 monooxygenases (P450s), ATP binding cassette transporters (ABCs), glutathione-S-transferases (GSTs), UDP-glycosyltransferases (UGTs) and carboxyl/choline esterases (CCEs).

Methods and findings

In this study, a high-quality near-chromosome level de novo genome assembly (as well as a mitochondrial genome assembly) for S. rueppellii has been generated using a hybrid approach with PacBio long-read and Illumina short-read data, followed by super scaffolding using Hi-C data. The final assembly achieved a scaffold N50 of 87Mb, a total genome size of 537.6Mb and a level of completeness of 96% using a set of 1,658 core insect genes present as full-length genes. The assembly was annotated with 14,249 protein-coding genes. Comparative analysis revealed gene expansions of CYP6Zx P450s, epsilon-class GSTs, dietary CCEs and multiple UGT families (UGT37/302/308/430/431). Conversely, ABCs, delta-class GSTs and non-CYP6Zx P450s showed limited expansion. Differences were seen in the distributions of resistance-associated gene families across subfamilies between S. rueppellii and some hemipteran crop pests. Additionally, S. rueppellii had larger numbers of detoxification genes than other pollinator species.

Conclusion and significance

This assembly is the first published genome for a predatory member of the Syrphidae family and will serve as a useful resource for further research into selectivity and potential tolerance of insecticides by beneficial predators. Furthermore, the expansion of some gene families often linked to insecticide resistance and selectivity may be an indicator of the capacity of this predator to detoxify IPM selective insecticides. These findings could be exploited by targeted insecticide screens and functional studies to increase effectiveness of IPM strategies, which aim to increase crop yields by sustainably and effectively controlling pests without impacting beneficial predator populations.
Transcriptome analysis reveals key developmental and metabolic regulatory aspects of oil palm (Elaeis guineensis Jacq.) during zygotic embryo development
Authors: Zhang Anni , Jin Longfei , Yarra Rajesh , Cao Hongxing , Chen Ping , John Martin Jerome Jeyakumar
Published: March 2022

Background

Oil palm is the most efficient oil-producing crop in the world, and the yield of palm oil is associated with embryonic development. However, a comprehensive understanding of zygotic embryo development at the molecular level remains elusive. In order to address this issue, we report the transcriptomic analysis of zygotic embryo development in oil palm, specifically focusing on regulatory genes involved in important biological pathways.

Results

In this study, three cDNA libraries were prepared from embryos at S1 (early-stage), S2 (middle-stage), and S3 (late-stage). There were 16,367, 16,500, and 18,012 genes characterized at the S1, S2, and S3 stages of embryonic development, respectively. A total of 1522, 2698, and 142 genes were differentially expressed in S1 vs S2, S1 vs S3, and S2 vs S3, respectively. Using Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify key genes and pathways. In the hormone signaling pathway, genes related to auxin antagonize the output of cytokinin which regulates the development of embryo meristem. The genes related to abscisic acid negatively regulating the synthesis of gibberellin were strongly up-regulated in the mid-late stage of embryonic development. The results were reported the early synthesis and mid-late degradation of sucrose, as well as the activation of the continuous degradation pathway of temporary starch, providing the nutrients needed for differentiation of the embryonic cell. Moreover, the transcripts of genes involved in fatty acid synthesis were also abundantly accumulated in the zygotic embryos.

Conclusion

Taken together, our research provides a new perspective on the developmental and metabolic regulation of zygotic embryo development at the transcriptional level in oil palm.
“Phoenix in Flight”: an unique fruit morphology ensures wind dispersal of seeds of the phoenix tree (Firmiana simplex (L.) W. Wight)
Authors: Gan Shi-Rui , Guo Jun-Cheng , Zhang Yun-Xiao , Wang Xiao-Fan , Huang Lan-Jie
Published: March 2022

Background

Many seed plants produce winged diaspores that use wind to disperse their seeds. The morphology of these diaspores is directly related to the seed dispersal potential. The majority of winged diaspores have flat wings and only seeds; however, some angiosperms, such as Firmiana produce winged fruit with a different morphology, whose seed dispersal mechanisms are not yet fully understood. In this study, we observed the fruit development of F. simplex and determined the morphological characteristics of mature fruit and their effects on the flight performance of the fruit.

Results

We found that the pericarp of F. simplex dehisced early and continued to unfold and expand during fruit development until ripening, finally formed a spoon-shaped wing with multiple alternate seeds on each edge. The wing caused mature fruit to spin stably during descent to provide a low terminal velocity, which was correlated with the wing loading and the distribution of seeds on the pericarp. When the curvature distribution of the pericarp surface substantially changed, the aerodynamic characteristics of fruit during descent altered, resulting in the inability of the fruit to spin.

Conclusions

Our results suggest that the curved shape and alternate seed distribution are necessary for the winged diaspore of F. simplex to stabilize spinning during wind dispersal. These unique morphological characteristics are related to the early cracking of fruits during development, which may be an adaptation for the wind dispersal of seeds.
Recombinant human endostatin combined with radiotherapy promotes cardiomyocyte apoptosis in rats via TGFβ1/Smads/CTGF signaling pathway
Authors: Ouyang Weiwei , Fu Shimei , Zhao Xing , Su Shengfa , Zhang Jun , Luo Daxian , Liu Lina , Ding Wenjin , Cao Dongdong , Liu Likun , He Zhixu , Lu Bing
Published: March 2022

Purpose

The aim of the present study was to investigate the efficacy of recombinant human endostatin (ES) (rh-ES) combined with radiation on rat cardiomyocyte apoptosis and the regulatory mechanism of transforming growth factor beta1 (TGF-β1)/Sma and Mad-related protein 3 (Smad3)/connective tissue growth factor (CTGF) signaling.

Method

The primary cardiomyocytes were isolated from neonatal Sprague–Dawley rats for culture in vitro and divided into blank control group (without treatment), 10 Gy radiation + siTGF-β1 siRNA (gene silencing) group, ES + siTGF-β1 siRNA group, and 10 Gy radiation + ES + siTGF-β1 siRNA group. Methyl thiazolyl tetrazolium assay was used to calculate the half-maximal inhibitory concentration (IC50) of rh-ES on cardiomyocytes. Adenoviral vector was constructed for virus packaging to silence TGF-β1 expression in cardiomyocytes. Quantitative real-time polymerase chain reaction and Western blot were carried out to analyze TGF-β1, Smad2, Smad3 and CTGF expression at both gene and protein levels. Flow cytometry and electron microscope were used to examine cell apoptosis.

Results

ES had a dose-dependent inhibitory effect on the proliferation of primary rat cardiomyocytes. ES combined with radiotherapy significantly inhibited cardiomyocyte proliferation and promoted cell apoptosis (P < 0.01). The gene and protein expression of TGF-β1, Smad2, Smad3 and CTGF were significantly up-regulated in primary cardiomyocytes transfected with TGF-β1 gene (P < 0.05).

Conclusion

The combination therapy with rh-ES and radiation can promote cardiomyocyte apoptosis and aggravate myocardial cell damage via TGF-β1/Smad3/CTGF signaling pathway.
Usability of novel major TraumaApp for digital data collection
Authors: Butler Joanna , Wright Evan , Longbottom Lucy , Whitelaw Alan S. , Thomson Kevin , Gordon Malcolm W. G. , Lowe David J.
Published: March 2022

Background

Delivery of major trauma care is complex and often fast paced. Clear and comprehensive documentation is paramount to support effective communication during complex clinical care episodes, and to allow collection of data for audit, research and continuous improvement. Clinical events are typically recorded on paper-based records that are developed for individual centres or systems. As one of the priorities laid out by the Scottish Trauma Network project was to develop an electronic data collection system, the TraumaApp was created as a data collection tool for major trauma that could be adopted worldwide.

Methods

The study was performed as a service evaluation based at the Queen Elizabeth University Hospital Emergency Department. Fifty staff members were recruited in pairs and listened to five paired major trauma standby and handover recordings. Participants were randomised to input data to the TraumaApp and one into the existing paper proforma. The time taken to input data add into was measured, along with time for clarifications and any errors made. Those using the app completed a System Usability Score.

Results

No statistically significant difference was demonstrated between times taken for data entry for the digital and paper documentation, apart from the Case 5 Handover (p < 0.05). Case 1 showed a significantly higher time for clarifications and number of errors with digital data collection (p = 0.01 and p = 1.79E-05 respectively). There were no other differences between data for the app and the proforma. The mean System Usability score for this cohort was 75 out of 100, with a standard deviation of 17 (rounded to nearest integer).

Conclusion

Digital real-time recording of clinical events using a tool such as the TraumaApp is comparable to completion of paper proforma. The System Usability Score for the TraumaApp was above the internationally validated standard of acceptable usability. There was no evidence of improvement in use over time or familiarity, most likely due to the brevity of the assessments and the refined user interface. This would benefit from further research, exploring data completeness and a potential mixed methods approach to explore training requirements for use of the TraumaApp.
The “unclear problem” category: an analysis of its patient and dispatch characteristics and its trend over time
Authors: Otten Sterre , Rehbock Cassandra , Krafft Thomas , Haugaard Martin Vang , Pilot Eva , Blomberg Stig Nikolaj , Christensen Helle Collatz
Published: March 2022

Background

An effective emergency medical dispatch process is vital to provide appropriate prehospital care to patients. It increases patient safety and ensures the sustainable use of medical resources. Although Copenhagen has a sophisticated emergency medical services (EMS) system with a significant focus on public welfare, more than 10% of emergency cases are still being categorized as an "unclear problem category" (UPC) and are thus not categorized as "symptom-specific". Therefore, the objective of this research is to gain a better understanding of the patient and dispatch characteristics of emergency cases categorized as "unclear".

Methods

This register-based study based on medical emergency cases data describes patient and dispatch characteristics of emergency cases categorized as “unclear” through the use of numbers and proportions. Moreover, these cases were compared to non UPC cases. Use of UPC was stratified by month to determine the impact of alerting medical dispatchers to reduce its use.

Results

From 296,398 included cases UPC accounted for 11.4% of the cases. The median age of those triaged with the UPC was 66 years vs 58 years for individuals triaged with other symptom-specific categories.

Moreover, after having been triaged with the UPC, 9,661 (34.7%) of the dispatched EMS vehicles ended up being cancelled. Sensitizing medical dispatchers about the use of the UPC likely contributed to the decreased use of the UPC over time.

Conclusion

The UPC has different dispatch characteristics than the symptom-specific categories, with potential negative effects on the medical dispatch process. Moreover, the median age of individuals triaged with the UPC is higher than those triaged with symptom-specific categories. Nonetheless, the use of the UPC decreased throughout the study period after the medical dispatchers were alerted about the implications of its use.
Management of intoxicated patients – a descriptive outcome analysis of 4,267 ICU patients
Authors: Rezar Richard , Jung Christian , Mamandipoor Behrooz , Seelmaier Clemens , Felder Thomas K. , Lichtenauer Michael , Wernly Sarah , Zwaag Samanta M. , De Lange Dylan W. , Wernly Bernhard , Osmani Venet
Published: March 2022

Introduction

Intoxications are common in intensive care units (ICUs). The number of causative substances is large, mortality usually low. This retrospective cohort study aims to characterize differences of intoxicated compared to general ICU patients, point out variations according to causative agents, as well as to highlight differences between survivors and non-survivors among intoxicated individuals in a large-scale multi-center analysis.

Methods

A total of 105,998 general ICU patients and 4,267 individuals with the admission diagnoses “overdose” and “drug toxicity” from the years 2014 and 2015 where included from the eICU Collaborative Research Database. In addition to comparing these groups with respect to baseline characteristics, intensive care measures and outcome parameters, differences between survivors and non-survivors from the intoxication group, as well as the individual groups of causative substances were investigated.

Results

Intoxicated patients were younger (median 41 vs. 66 years; p<0.001), more often female (55 vs. 45%; p<0.001), and normal weighted (36% vs. 30%; p<0.001), whereas more obese individuals where observed in the other group (37 vs. 31%; p<0.001). Intoxicated individuals had a significantly lower mortality compared to general ICU patients (1% vs. 10%; aOR 0.07 95%CI 0.05-0.11; p<0.001), a finding which persisted after multivariable adjustment (aOR 0.17 95%CI 0.12-0.24; p<0.001) and persisted in all subgroups. Markers of disease severity (SOFA-score: 3 (1-5) vs. 4 (2-6) pts.; p<0.001) and frequency of vasopressor use (5 vs. 15%; p<0.001) where lower, whereas rates of mechanical ventilation where higher (24 vs. 26%; p<0.001) in intoxicated individuals. There were no differences with regard to renal replacement therapy in the first three days (3 vs. 4%; p=0.26). In sensitivity analysis (interactions for age, sex, ethnicity, hospital category, maximum initial lactate, mechanical ventilation, and vasopressor use), a trend towards lower mortality in intoxicated patients persisted in all subgroups.

Conclusion

This large-scale retrospective analysis indicates a significantly lower mortality of intoxicated individuals compared to general ICU patients.
The Procalcitonin-guided Antibiotics in Respiratory Infections (PARI) project in general practice – a study protocol
Authors: Filipsen Nadia , Bro Holger , Bjerrum Lars , Jensen Jens-Ulrik Staehr , Aabenhus Rune
Published: March 2022

Background

Antibiotic resistance is a global health challenge and the close correlation between antibiotic use and the development of resistance makes it essential to maintain a rational use of antibiotics. Most antibiotics are prescribed in general practice against acute respiratory tract infections (ARTI), even though most of these infections are of viral etiology. Thus, a safe method to substantially reduce unnecessary use of antibiotics in general practice is needed. Procalcitonin (PCT) is a precursor protein with very low circulating levels in the blood under physiological conditions. However, in response serious bacterial infection the level of PCT in the blood may increase significantly. Until recently, quantitative analyses of PCT was performed in hospital laboratories, impeding the implementation of PCT in primary care. Our aim is to determine whether it is possible to lower the use of antibiotics in patients presenting with symptoms of ARTI, without significantly prolonging the period of illness, by using a newly released PCT point-of-care test in general practice.

Methods

The Procalcitonin-Guided Antibiotics in Respiratory Infections (PARI) study is a randomized, single-blinded, non-inferiority, multi-practice intervention study comparing a PCT-group to a control group. Patients (N = 508) will be randomly assigned 1:1 to standard care or to the PCT group. The primary outcomes the duration of illness and symptoms from ARTI measured with the Acute Respiratory Tract Infection Questionnaire. Secondary outcomes include (1) Number of participants in each trial arm exposed to antibiotic treatment at index consultation (day 1) and within 30 days, (2) Number of participants in each trial arm with side effects from antibiotic treatment within 14 days, (3) Number of participants in each trial arm with re-consultations within 30 days, (4) Number of participants in each trial arm admitted to hospital (including diagnosis and mortality) within 30 days, (5) Characterization of biomarker (CRP and PCT) level at index consultation. Tertiary outcomes include patient and general practitioner satisfaction with the use of the PCT point-of-care test, and long-term follow-up.

Discussion

To our knowledge, this is the first study to examine a PCT point-of-care test in general practice with the aim of reducing the use of antibiotics in patients with symptoms of ARTI. Results of this study may prove important in targeting antibiotic treatment only to those patients who need it, thus contributing to limiting the spread of antibiotic resistance.

Trial registration

ClinicalTrials.gov Identifier: NCT04216277, date of registration: 2. of January 2020.
Satisfaction of primary care physicians towards initiation of phone consultations during the COVID-19 pandemic management in Qatar: a cross-sectional study
Authors: Neshnash Marwa , Metwally Nourhan , Ismail Mansoura , Joudeh Anwar , Al-Dahshan Ayman , Sharif Anna Ramish , Sharief Najma , Nur Muna , Selim Nagah
Published: March 2022

Objectives

To assess primary care physicians’ satisfaction towards initiation of phone consultation during COVID-19 pandemic management in Qatar and to identify the factors associated with dis/satisfaction.

Design

A cross-sectional web-based survey was conducted from 1 June to 30 July 2020.

Setting

All the available 27 public primary healthcare centers in Qatar at the time of the study.

Participants

Two hundred ninety-four primary care physicians working in the publicly run primary healthcare corporation in Qatar.

Primary outcome measures

Overall satisfaction of primary care physicians with the initiation of phone consultation during the COVID-19 pandemic in Qatar and their satisfaction towards each aspect of this management.

Results

Two hundred thirty-nine primary care physicians participated in the survey with a response rate of 53.1%. Overall, about 45% and 21% of respondents agreed that COVID-19 disease management has highly impacted and very highly impacted their daily practice, respectively. More than half of the physicians (59.9%) indicated being satisfied/highly satisfied with the initiation of telephone consultation service. On the other hand, few physicians were satisfied (14.3%) or highly satisfied (3.4%) with conducting telephone consultations with patients who lack previous electronic medical records. Also, only 20.3% and 3.8% of physicians were satisfied and highly satisfied with the lack of physical examination in telephone consultations, respectively. On bivariate analysis, primary care physicians’ age was significantly associated with the perceived level of impact of COVID-19 management on daily practice (P = 0.03). There was no significant association between participants’ characteristics and the level of satisfaction toward telephone consultations. On the other hand, there was a statistically significant association between physicians’ age (p = 0.048) and gender (p = 0.014) and their level of satisfaction toward communication and support.
Do changes in frailty, physical functioning, and cognitive functioning predict mortality in old age? Results from the Longitudinal Aging Study Amsterdam
Authors: Kusumastuti Sasmita , Hoogendijk Emiel O. , Gerds Thomas A. , Lund Rikke , Mortensen Erik L. , Huisman Martijn , Westendorp Rudi G. J.
Published: March 2022

Background

The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using various health indicators as well as changes in these indicators for predicting mortality remains unclear. The aim of this study was to investigate whether changes in health indicators such as frailty and physical performance improve mortality predictions in old age.

Methods

This is a population based prospective cohort study on 995 community-dwelling people aged 68–92 years from the Longitudinal Aging Study Amsterdam. Two measurements at a three-year interval (1995/1996 and 1998/1999) were available for the frailty index, frailty phenotype, grip strength, walking speed, and Mini-Mental State Examination (MMSE). Cox regression was used to analyze mortality risks associated with the current health status and changes in health, with mortality data up to 2017. The extent to which these health indicators improved mortality predictions compared to models with age and sex only was assessed by the area under the receiver operating characteristic curve (AUC).

Results

The AUC of age and sex for five-year mortality was 72.8% (95% CI 69.0 – 76.5) and was the lowest in the oldest old (age > 80.5 years). The added AUC of the current status of health indicators ranged from 0.7 to 3.3%. The added AUC of the three-year change was lower, ranging from -0.0 to 1.1%, whereas the added AUC of three-year change and current status combined was similar to current status alone, ranging from 0.6 to 3.2%. Across age, the added AUC of current status was highest in the oldest old, however there was no such pattern using three-year change. Overall, the frailty index appeared to improve mortality predictions the most, followed by the frailty phenotype, MMSE, grip strength, and walking speed.

Conclusions

Current health status improved mortality predictions better than changes in health. Its contribution was highest in the oldest old, but the added value to models with age and sex only was limited.
Comparative study of the bacterial distribution and antimicrobial susceptibility of uropathogens in older and younger patients with urinary stones
Authors: Gu Jie , Song Ping , Chen Xiong , Yang Zhiming , Zhang Xiaobo , Bai Yao
Published: March 2022

Background

This study compared the bacterial spectrum and antibiotic susceptibility of uropathogens in older and younger patients with urinary stones to provide appropriate antibiotic management.

Methods

We retrospectively reviewed urinary tract infection patients with urolithiasis, presented to Xiangya Hospital from March 2014 to April 2021. Patients were divided into older and younger groups according to 60 years of age. The bacterial spectrum and drug sensitivity of uropathogens were compared.

Results

A total of 542 strains of uropathogens (177 in older and 365 in younger groups) were isolated from 507 patients. E. coli (41.8% vs 43.6%) remains the most common pathogen, followed by E. faecalis (6.2% vs 9.6%) in older and younger groups, respectively. Particularly, K. pneumoniae was significantly more frequent in older (9.6%) than in younger group (4.7%, P < .05). E. faecium was substantially more prevalent in older group (6.2%) than in younger group (2.7%, P < .05). The proportion of males increased in older patients (47.3%) than in younger patients (34.9%, P = 0.007). In both groups, major Gram-negative bacteria (E. coli and K. pneumoniae) revealed a high sensitivity over 70% to piperacillin/tazobactam, imipenem and amikacin, whereas the resistance level was high to penicillin, tetracycline and vancomycin. Major Gram-positive (E. faecalis and E. faecium) isolates demonstrated high sensitivity of over 50% to gentamicin and vancomycin in both groups. Furthermore, uropathogens isolated from younger urolithiasis patients were more susceptible to antimicrobials than those isolated from older patients.

Conclusions

The male increased in the older urolithiasis patients with UTI and uropathogens microbial spectrum in older urolithiasis patients are different from younger. High susceptibility and age should be utilized in empirical antibiotic selection to avoid increased multidrug-resistant bacteria.
Persistent cough and asthma-like symptoms post COVID-19 hospitalization in children
Authors: Esmaeilzadeh Hossein , Sanaei Dashti Anahita , Mortazavi Negar , Fatemian Hossein , Vali Mohebat
Published: March 2022

Backgrounds

Respiratory viruses are the main triggers of asthma. Coronavirus is shown to contribute to respiratory tract infections that can lead to prolonged cough and asthma.

Objectives

Present study aimed to determine the risk of developing Persistent cough and asthma-like symptoms in hospitalized children due to COVID-19.

Methods

This prospective study was carried out in a tertiary referral center. During the COVID-19 pandemic, 69 hospitalized pediatric patients admitted with COVID-19 were observed from February 2020 to January 2021. Clinical and laboratory data were recorded, and after discharge, patients were followed and visited for cough and asthma evaluation one, 2 and 6 months later. Patients with asthma-like diagnoses in follow up defined as asthma-like groups, and patients without any sign of asthma were categorized as the non-asthma group. Asthma-like co-morbids and risk factors were evaluated and compared between the two groups.

Results

In follow-up, most of the COVID-19 hospitalized patients (N = 42) (58.5%) were not affected by asthma-like symptoms. 60.9% of the COVID-19 patients were male. The asthma-like group cases had a significantly familial history of asthma (63.0%), past medical history of asthma (33.3%), and Allergic rhinitis (85.2%). Rates of signs and symptoms during hospitalization were significantly higher in patients with COVID-19 and past medical history of asthma.

Conclusions

We found an asthma-like prevalence of 41.5% in the cohort of COVID-19 hospitalized children. Family history of asthma and previous history of asthma and allergic rhinitis are risk factors for asthma-like after COVID-19 hospitalization. COVID-19 presentations are more severe in the asthma-like group.
Prediction of midline shift after media ischemia using computed tomography perfusion
Authors: Müller Sebastian Johannes , Khadhraoui Eya , Ernst Marielle Sophie , Riedel Christian Heiner
Published: March 2022

Background

Decision-making about the indication for decompressive hemicraniectomy in cases with malignant infarction in the territory of the middle cerebral artery (MCA) is still a matter of debate. Some scores have been introduced and tested, most of them are midline-shift dependent. We introduce the Kinematics of malignant MCA infarction (KM) index, which can be calculated based on an initial computed tomography perfusion scan and the chosen therapy (lysis/thrombectomy/conservative) in order to estimate the maximum midline-shift in the subsequent 6 days.

Methods

We retrospectively analyzed patients with middle cerebral artery infarction who had a non-enhanced computed tomography (CT) scan, CT angiography and a CT perfusion scan in the acute setting and who presented in our emergency room between 2015 and 2019. 186 patients were included. Midline shift was measured on follow-up imaging between days 0 and 6 after stroke. We evaluated Pearson’s correlation between the KM index and the amount of midline shift.

Results

The mean KM index of all patients was 1.01 ± 0.09 (decompressive hemicraniectomy subgroup 1.13 ± 0.13; midline shift subgroup 1.18 ± 0.13). The correlation coefficient between the KM index and substantial midline-shift was 0.61, p < 0.01 and between KM index and decompressive hemicraniectomy or death 0.47; p < 0.05. KM index > 1.02 shows a sensitivity of 92% (22/24) and a specificity of 78% (126/162) for detecting midline shifts. The area under curve of the receiver operator characteristics was 91% for midline shifts and 86% for the occurrence of decompressive hemicraniectomy or death.

Conclusion

In this retrospective study, KM index shows a strong correlation with significant midline-shift. The KM index can be used for risk classification regarding herniation and the need of decompressive hemicraniectomy.
Opicapone versus placebo in the treatment of Parkinson’s disease patients with end-of-dose motor fluctuation-associated pain: rationale and design of the randomised, double-blind OCEAN (OpiCapone Effect on motor fluctuations and pAiN) trial
Authors: Chaudhuri K. Ray , Odin Per , Ferreira Joaquim J. , Antonini Angelo , Rascol Olivier , Kurtis Mónica M. , Storch Alexander , Bannister Kirsty , Soares-da-Silva Patrício , Costa Raquel , Magalhães Diogo , Rocha José Francisco
Published: March 2022

Background

Optimisation of dopaminergic therapy may alleviate fluctuation-related pain in Parkinson’s disease (PD). Opicapone (OPC) is a third-generation, once-daily catechol-O-methyltransferase inhibitor shown to be generally well tolerated and efficacious in reducing OFF-time in two pivotal trials in patients with PD and end-of-dose motor fluctuations. The OpiCapone Effect on motor fluctuations and pAiN (OCEAN) trial aims to investigate the efficacy of OPC 50 mg in PD patients with end-of-dose motor fluctuations and associated pain, when administered as adjunctive therapy to existing treatment with levodopa/dopa decarboxylase inhibitor (DDCi).

Methods

OCEAN is a Phase IV, international, multicentre, randomised, double-blind, placebo-controlled, parallel-group, interventional trial in PD patients with end-of-dose motor fluctuations and associated pain. It consists of a 1-week screening period, 24-week double-blind treatment period and 2-week follow-up period. Eligible patients will be randomised 1:1 to OPC 50 mg or placebo once daily while continuing current treatment with levodopa/DDCi and other chronic, stable anti-PD and/or analgesic treatments. The primary efficacy endpoint is change from baseline in Domain 3 (fluctuation-related pain) of the King’s Parkinson’s disease Pain Scale (KPPS). The key secondary efficacy endpoint is change from baseline in Domain B (anxiety) of the Movement Disorder Society-sponsored Non-Motor rating Scale (MDS-NMS). Additional secondary efficacy assessments include other domains and total scores of the KPPS and MDS-NMS, the Parkinson’s Disease Questionnaire (PDQ-8), the MDS-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts III and IV, Clinical and Patient’s Global Impressions of Change, and change in functional status via Hauser’s diary. Safety assessments include the incidence of treatment-emergent adverse events. The study will be conducted in approximately 140 patients from 50 clinical sites in Germany, Italy, Portugal, Spain and the United Kingdom. Recruitment started in February 2021 and the last patient is expected to complete the study by late 2022.

Discussion

The OCEAN trial will help determine whether the use of adjunctive OPC 50 mg treatment can improve fluctuation-associated pain in PD patients with end-of-dose motor fluctuations. The robust design of OCEAN will address the current lack of reliable evidence for dopaminergic-based therapy in the treatment of PD-associated pain.

Trial registration

EudraCT number 2020–001175-32; registered on 2020-08-07.