bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ozone Exposure and Asthma Attack in Children
Authors: Huang Wanting , Wu Jinzhun , Lin Xiaoliang 
Published: April 2022

BackgroundIncreasing evidence indicated that ozone (O3) exposure could trigger asthma attacks in children. However, the effect of O3 at low concentrations is uncertain.PurposeThis study aimed to explore the effects of O3 exposure at low concentrations on asthma attacks in children.MethodsA total of 3,475 children with asthma attacks from the First Affiliated Hospital of Xiamen University were available for the analyses. Air pollution data and meteorological data in Xiamen during 2016–2019 were also collected. A case-crossover design and conditional logistic regression models were conducted to evaluate the association between asthma attacks and outdoor air pollution with lag structures (from lag 0 to lag 6) in both single and multi-pollutant models. Furthermore, we estimated the influence of various levels of O3 exposure on an asthma attack in three groups categorized by maximum daily 8-h sliding average ozone (O3-8 h) (O3-8 h ≥ 100 μg/m3, O3-8 h: 80–99 μg/m3, O3-8 h &lt; 80 μg/m3).ResultsFor both single-pollutant models and multi-pollutant models, when O3-8 h was higher than 80 μg/m3, O3 exposure was increased the risk of acute asthma attacks on each day of lag. The effect of O3 on children with asthma was significant when O3 concentration was higher than 100 μg/m3.ConclusionO3 concentration above 80 μg/m3 contributed to an increased risk of asthma attacks in children.
Efficacy and Outcome of Remdesivir and Tocilizumab Combination Against Dexamethasone for the Treatment of Severe COVID-19: A Randomized Controlled Trial
Authors: Mohiuddin Chowdhury Abu Taiub Mohammed , Kamal Aktar , Abbas Kafil Uddin , Talukder Shubhashis , Karim Md Rezaul , Ali Md. Ahsan , Nuruzzaman Md. , Li Yarui , He Shuixiang 
Published: April 2022

Objective: In this study, we investigated the efficacy and safety of remdesivir and tocilizumab combination therapy against dexamethasone for the management of severe COVID-19 patients.Methods: This was a multicenter study. Cases were randomly chosen and divided into two groups using an odd–even ratio of 1:1 applied to the hospital registration number. Group A received remdesivir [5 mg/kg (&lt;40 kg) or 200 mg (&gt;40 kg) on day 1 and then 2.5 mg/kg (&lt;40 kg) or 100 mg (&gt;40 kg) daily] + tocilizumab [8 mg/kg up to 800 mg highest 12 h apart], and group B was the control and received dexamethasone 6 mg/day. In addition, a broad-spectrum antibiotic and other essential treatments were received by all patients. To evaluate the mortality risk, the sequential organ failure assessment (SOFA) score was calculated on day-1. Treatment outcomes were measured as time to clinical improvement; mortality rate; duration of ICU stay; total period of hospitalization; the rate of (Supplementary Material) oxygen use; time to clinical failure; National Early Warning Score-2 (NEWS), and the percentage of lung recovery on CT of chest on discharge. Clinical trial registration ID: NCT04678739.Results: Remdesivir-Tocilizumab group had a lower mortality rate (25.49%) than the control (30.77%). The time to clinical improvement (Group A-9.41; B-14.21 days), NEWS-2 on discharge (Group A-0.89; B-1.2), duration of ICU stay (Group A-7.68; B-10.58), and duration of hospitalization (Group A-9.91; B-14.68) were less in the treatment group. Group A had a better percentage of lung recovery on chest CT than the control (Group A-22.13; B-11.74). All these differences were statistically significant (p= &lt;0.05) in a t-test. However, no significant survival benefit was found among the study groups in Kaplan–Meier survival analysis, p = 0.739.Conclusion: The remdesivir–tocilizumab combination had preferable outcomes compared to the dexamethasone therapy for the treatment of severe COVID-19 concerning mortality rate and clinical and pulmonary improvement, although it did not demonstrate a significant survival benefit.Clinical Trial Registration:https://clinicaltrials.gov, NCT04678739.
Impact of Three Safety Interventions Targeting Off-Label Use of Immediate-Release Fentanyl on Prescription Trends: Interrupted Time Series Analysis
Authors: García-Sempere Aníbal , Hurtado Isabel , Peiró Salvador , Sánchez-Sáez Francisco , Rodríguez-Bernal Clara Liliana , Puig-Ferrer Magda , Escolano Manuel , Sanfélix-Gimeno Gabriel 
Published: April 2022

Background: The Spanish health authorities are concerned by the off-label use of immediate-release formulations of fentanyl (IRF) in noncancer pain and cancer pain in patients with no chronic pain therapy.Aim: To evaluate the impact of different interventions to improve appropriateness of IRF prescription on off-label prescription.Patients and methods: We used interrupted time series (ITS) to estimate immediate and trend changes of IRF prescription for noncancer pain (NCP) and breakthrough cancer pain (BCP) in patients with and without chronic cancer pain therapy associated with two medication reviews (I1 and I2) and the issue of a safety warning letter (I3) with data from a Spanish region with 5 million inhabitants, from 2015 to 2018.Results: The use of IRF for NCP in the region Valencia was reduced from about 1,800 prescriptions per week to around 1,400. The first medication review was followed by an immediate level change of −192.66 prescriptions per week (p &lt; 0.001) and a downward trend change of −6.75 prescriptions/week (p &lt; 0.001), resulting in a post-intervention trend of −1.99 (p &lt; 0.001). I2 was associated with a trend change of -23.07 (p &lt; 0.001) prescriptions/week. After I3, the trend changed markedly to 27.23 additional prescriptions/week, for a final post-intervention trend of 2.17 (p &lt; 0.001). Controlled-ITS provided comparable results. For potentially inappropriate BCP use, the second medication review was followed by a downward, immediate level change of −10.10 prescriptions/week (p = 0.011) and a trend change of 2.31 additional prescriptions/week (p &lt; 0.001) and the issue of the safety warning (I3) was followed by a downward trend change of −2.09 prescriptions/week (p = 0.007).Conclusion: Despite IRF prescription for NCP decreased, the interventions showed modest and temporary effect on off-label prescription. Our results call for a review of the design and implementation of safety interventions addressing inappropriate opioid use.
Registered Clinical Trials Comprising Pregnant Women in China: A Cross-Sectional Study
Authors: Zhao Yi , Du Guiping , Luan Xiaofei , Yang Hui , Zhang Qiongguang , Zhang Zhengfu , Wang Subiao 
Published: April 2022

Background: In this study, an investigation was conducted on clinical drug trials comprising pregnant women in China that provided data on the quantity, properties, source of funding, and geographical distribution regarding registration and post-marketing studies.Methods: We conducted a cross-sectional descriptive study of clinical trials of pregnant women in China on 30 December 2021, and it was registered on the official Drug Clinical Trial Information Management Platform (ChiCTR) (http://www.chinadrugtrials.org.cn) established by the State Food and Drug Administration of China (Chinese FDA).Results: This study encompassed 72 registered trials (0.46%, 72/15,539) for data analysis. Of these trials, 43.1% of trials were started between 2013 and 2016, and nearly half of the trials (48.6%) were completed. Industries were listed as the primary sponsor for 95.8% trials. Economically developed eastern China and northern China, accounting for 69.5% of the 72 registered trials, were the most frequently identified study locations. Regarding study designs of these trials, more than half of the trials (70.8%) were randomized, 61.1% were a parallel assignment, 33.3% were phase 3, and half of the trials (54.2%) were open label. In total, 23 trials met the requirements after excluding trials of cancer and/or of postmenopausal women, accounting for 0.15% of the 15,539 registered trials in the ChiCTR websites. Of the 72 clinical trials, 54 drugs for 18 indications were included. Of these indications, the highest proportion of the trials is osteoporosis (27.8%), followed by cancer (22.2%), assisted reproduction (13.9%), and other indications (13.9%).Conclusion: This survey revealed a significant shortage of the development, evaluation, and safety trials of pregnancy-related drugs in China. Modifying or adding legislation and providing financial incentives may therefore encourage pharmaceutical companies to conduct additional clinical trials on pregnant women.
New Therapeutic Horizon of Graves’ Hyperthyroidism: Treatment Regimens Based on Immunology and Ingredients From Traditional Chinese Medicine
Authors: He Qiongyao , Dong Hui , Gong Minmin , Guo Yujin , Xia Qingsong , Gong Jing , Lu Fuer 
Published: April 2022

Graves’ disease is an autoimmune disease characterized by goiter and hyperthyroidism, and 25% patients develop GO. Traditional treatment options, such as antithyroid drugs, radioiodine or thyroidectomy, have remained largely unchanged over the past 70 years. For many patients, there is a high rate of recurrence after antithyroid drugs and lifelong hypothyroidism after ablation and thyroidectomy. The symptoms and quality of life of some patients have not been effectively improved. The clinical demand for new therapeutic regimens, coupled with a deeper understanding of the pathophysiology and immunobiology of Graves’ disease, has led to the emergence of several new therapeutic ideas, including biologics, small molecule peptides, immunomodulators and teprotumumab, a specific antibody targeting IGF-1R. Besides, the elements of TCM have attracted more and more interests in modern medicine, because some effective components have been successfully used in the treatment of autoimmune diseases. Based on the pathophysiology and efficacy of clinical management and treatment in Graves’ hyperthyroidism, here we review the new strategies under investigation and summarize the effective components of traditional Chinese medicine used for Graves’ hyperthyroidism, and explore their mechanisms. These therapies have opened a new window for the treatment of Graves’ disease, but the exact mechanism and the research direction still need to be further explored.
Non-targeted Metabolomics Analysis Based on LC–MS to Assess the Effects of Different Cold Exposure Times on Piglets
Authors: Chen Yong , Ji Hong , Guo Jingru , Chen Yan , Li Wenjie , Wang Shengping , Zhen Li 
Published: April 2022

Pigs are susceptible to low temperature conditions, and cold stress causes metabolic changes in the body to increase heat production as an adaption to adverse environments. To characterize and validate different metabolites in piglet livers at different cold exposure times, sixteen 30-day-old male weaned piglets with similar weights were randomly divided into four groups: the normal temperature group (24 ± 2°C, NT) and cold exposure (4 ± 2°C) 2-h group (CS2), 6-h group (CS6), and 12-h group (CS12). At the end of the experiment, the liver samples were analyzed using systemic non-targeted metabolomics. Eight known differentially abundant metabolites (farnesyl pyrophosphate, isocitrate, triethanolamine, phenylethylamine, deoxynosine, citric acid, maltotriose, and epinephrine) were observed between the CS groups and the control group in positive and negative ion modes. The eight main differentially abundant metabolites involved in seven metabolite classifications. Metabolic pathways and enrichment analyses revealed that the pathways involved three KEGG pathway classifications. Most of the pathways were related to amino acid or energy metabolism. Moreover, the metabolic pathways were not identical under different cold exposure times, with those following 2 and 6 h of cold exposure more related to carbohydrates and energy production and those following 12 h of cold exposure more related to the metabolism connected with epinephrine. Thus, under different cold exposure times, the metabolite profiles and metabolic pathways differed.
Developing Scotland’s First Green Health Prescription Pathway: A One-Stop Shop for Nature-Based Intervention Referrals
Authors: Marx Viola , More Kimberly R. 
Published: April 2022

IntroductionLifestyle modifications are part of comprehensive treatment plans to help manage the symptoms of pre-existing chronic conditions. However, behavior change is notoriously difficult as patients often lack the necessary support. The present manuscript outlines the development of a Green Health Prescription pathway that was designed to link patients with appropriate lifestyle interventions (i.e., nature-based interventions) and to support attendance. Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was undertaken in three focus groups (i.e., National Health Service healthcare professionals, service-users, and nature-based intervention delivery partners) to highlight areas of strength and weakness within the proposed pathway prior to delivery. The SWOT analyses revealed that the pathway was supported by all three focus groups. Weaknesses and threats were identified including sustainability of nature-based interventions in terms of funding, the need to connect patients with appropriate interventions based on their physical and mental health needs, and the requirement to have a “one-stop shop” for information to ensure that the pathway was accessible for all service-users and healthcare professionals. Results were addressed and considered throughout the development of the pathway.DiscussionThe Green Health Prescription pathway was launched in 2019 and gave patients the ability to receive a prescription from a healthcare professional, community service, or to self-refer. The pathway allows patients to contact a consultant, via a telephone service, who is trained to match them with a programme that the patient believes will be enjoyable and that fits their treatment needs. Data collection to assess the efficacy of the pathway is ongoing.
Detection of Schizophrenia Cases From Healthy Controls With Combination of Neurocognitive and Electrophysiological Features
Authors: Tian Qing , Yang Ning-Bo , Fan Yu , Dong Fang , Bo Qi-Jing , Zhou Fu-Chun , Zhang Ji-Cong , Li Liang , Yin Guang-Zhong , Wang Chuan-Yue , Fan Ming 
Published: April 2022

BackgroundThe search for a method that utilizes biomarkers to identify patients with schizophrenia from healthy individuals has occupied researchers for decades. However, no single indicator can be employed to achieve the good in clinical practice. We aim to develop a comprehensive machine learning pipeline based on neurocognitive and electrophysiological combined features for distinguishing schizophrenia patients from healthy people.MethodsIn the present study, 69 patients with schizophrenia and 50 healthy controls participated. Neurocognitive (contains seven specific domains of cognition) and electrophysiological [prepulse inhibition, electroencephalography (EEG) power spectrum, detrended fluctuation analysis, and fractal dimension (FD)] features were collected, all these features were taken together to generate the identification models of schizophrenia by applying logistics, random forest, and extreme gradient boosting algorithm. The classification capabilities of these models were also evaluated.ResultsBoth the neurocognitive and electrophysiological feature sets showed a good classification effect with the highest accuracy greater than 85% and AUC greater than 90%. Specifically, the performances of the combined neurocognitive and electrophysiological feature sets achieved the highest accuracy of 93.28% and AUC of 97.91%. The extreme gradient boosting algorithm as a whole presented more stably and precisely in classification efficiency.ConclusionThe highest classification accuracy of 93.28% by combination of neurocognitive and electrophysiological features shows that both measurements are appropriate indicators to be used in discriminating schizophrenia patients and healthy individuals. Also, among three algorithms, extreme gradient boosting had better classified performances than logistics and random forest algorithms.
Association Between Sense of Coherence and Frailty: A Cross-Sectional Study in China
Authors: Chen Hao , Fu Hua , Ye Bo , Wang Yi , Yan Huihui , Chen Yingwei , Xu Jixiang , Nie Xin , Gao Junling 
Published: April 2022

PurposeFrailty is an emerging global public health burden. Most existing studies have focused on risk factors for frailty, focusing less on protective factors against frailty. This study aims to examine the association between the sense of coherence (SOC), the most common construct of salutogenesis and frailty status among community-dwelling old adults.MethodA cross-sectional study was conducted among 7,970 old adults aged ≥65 years in three cities in China from June 2019 to October 2020. Frailty was operationalised as the sum of self-reported fatigue, resistance, ambulation, illness, and loss of weight (FRAIL scale). The χ2 test was used to analyse the distribution difference of frailty in demographic, behavioural, and SOC levels. Confounder-adjusted multinomial logistic regression was used to examine the association between SOC and frailty.ResultsThe prevalence of pre-frailty and frailty was 43.1 and 8.0%, respectively. The results of the confounder-adjusted regression showed that older adults with moderate-level SOC (odds ratio, OR: 0.61, 95% CI: 0.54–0.69) and strong-level SOC (OR: 0.55, 0.48–0.64) had lower odds of being pre-frail compared to those with weak SOC. It also showed that older adults with moderate-level SOC (OR: 0.32, 95% CI: 0.27–0.40) and strong-level SOC (OR: 0.22, 95% CI: 0.16–0.29) had lower odds of being frail compared to those with weak SOC.ConclusionSOC may be a protective factor against frailty. Improving SOC may be a strategy to prevent frailty among Chinese community-dwelling older adults.
Functional and Structural Brain Connectivity in Children With Bilateral Cerebral Palsy Compared to Age-Related Controls and in Response to Intensive Rapid-Reciprocal Leg Training
Authors: Damiano Diane L. , Pekar James J. , Mori Susumu , Faria Andreia Vasconcellos , Ye X. , Stashinko Elaine , Stanley Christopher J. , Alter Katharine E. , Hoon Alec H. , Chin Eric M. 
Published: April 2022

BackgroundCompared to unilateral cerebral palsy (CP), less is known about brain reorganization and plasticity in bilateral CP especially in relation or response to motor training. The few trials that reported brain imaging results alongside functional outcomes include a handful of studies in unilateral CP, and one pilot trial of three children with bilateral CP. This study is the first locomotor training randomized controlled trial (RCT) in bilateral CP to our knowledge reporting brain imaging outcomes.MethodsObjective was to compare MRI brain volumes, resting state connectivity and white matter integrity using DTI in children with bilateral CP with PVL and preterm birth history (&lt;34 weeks), to age-related controls, and from an RCT of intensive 12 week rapid-reciprocal locomotor training using an elliptical or motor-assisted cycle. We hypothesized that connectivity in CP compared to controls would be greater across sensorimotor-related brain regions and that functional (resting state) and structural (fractional anisotropy) connectivity would improve post intervention. We further anticipated that baseline and post-intervention imaging and functional measures would correlate.ResultsImages were acquired with a 3T MRI scanner for 16/27 children with CP in the trial, and 18 controls. No conclusive evidence of training-induced neuroplastic effects were seen. However, analysis of shared variance revealed that greater increases in precentral gyrus connectivity with the thalamus and pons may be associated with larger improvements in the trained device speed. Exploratory analyses also revealed interesting potential relationships between brain integrity and multiple functional outcomes in CP, with functional connectivity between the motor cortex and midbrain showing the strongest potential relationship with mobility. Decreased posterior white matter, corpus callosum and thalamic volumes, and FA in the posterior thalamic radiation were the most prominent group differences with corticospinal tract differences notably not found.ConclusionsResults reinforce the involvement of sensory-related brain areas in bilateral CP. Given the wide individual variability in imaging results and clinical responses to training, a greater focus on neural and other mechanisms related to better or worse outcomes is recommended to enhance rehabilitation results on a patient vs. group level.
Effect of Haptic Training During Manual Wheelchair Propulsion on Shoulder Joint Reaction Moments
Authors: Aissaoui Rachid , Gagnon Dany 
Published: April 2022

BackgroundManual wheelchair propulsion remains a very ineffective means of locomotion in terms of energy cost and mechanical efficiency, as more than half of the forces applied to the pushrim do not contribute to move the wheelchair forward. Manual wheelchair propulsion training using the haptic biofeedback has shown an increase in mechanical efficiency at the handrim level. However, no information is available about the impact of this training on the load at the shoulders. We hypothesized that increasing propulsion mechanical efficiency by 10% during propulsion would not yield clinically significant augmentation of the load sustained at the shoulders.MethodsEighteen long-term manual wheelchair users with a spinal cord injury propelled a manual wheelchair over a wheelchair simulator offering the haptic biofeedback. Participants were asked to propel without the Haptic Biofeedback (HB) and, thereafter, they were subjected to five training blocks BL1–BL5 of 3 min in a random order with the haptic biofeedback targeting a 10% increase in force effectiveness. The training blocs such as BL1, BL2 BL3, BL4, and BL5 correspond, respectively, to a resistant moment of 5, 10, 15, 20, and 25%. Pushrim kinetics, shoulder joint moments, and forces during the propulsive cycle of wheelchair propulsion were assessed for each condition.ResultsThe tangential force component increases significantly by 74 and 87%, whereas value for the mechanical effective force increases by 9% between the pretraining and training blocks BL3. The haptic biofeedback resulted in a significant increase of the shoulder moments with 1–7 Nm.ConclusionIncreases in shoulder loads were found for the corresponding training blocks but even though the percentage of the increase seems high, the amplitude of the joint moment remains under the values of wheelchair propulsion found in the literature. The use of the HB simulator is considered here as a safe approach to increase mechanical effectiveness. However, the longitudinal impact of this enhancement remains unknown for the impact on the shoulder joint. Future studies will be focused on this impact in terms of shoulder risk injury during manual wheelchair propulsion.