bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Current State of Pharmacovigilance System in Pakistan Using Indicator-Based Assessment Tool
Authors: Khan Muhammad Akhtar Abbas , Hamid Saima , Ur-Rehman Tofeeq , Babar Zaheer-Ud-Din 
Published: January 2022

Objectives: Pakistan felt the need for an effective and robust pharmacovigilance (PV) system after one of the deadliest drug-related tragedies causing more than 300 deaths in 2012. The country set up its national PV center in 2015 and joined WHO’s Program for International Drug Monitoring (PIDM) in 2018 as a full member. The current study was aimed to evaluate the PV system’s functionality, identify the gaps, areas of improvement, and a strategy to lead a functional PV system in Pakistan.Methods: The descriptive cross-sectional study was conducted by providing an interviewer-administered questionnaire of the PV system across Pakistan by utilizing the Indicator based Pharmacovigilance assessment tool (IPAT). By a convenience sampling method 36 study participants were selected from the Drug Regulatory Authority of Pakistan (DRAP), drug administration of provincial health departments of 4 provinces and federally affiliated areas, 5 national public health programs, and 23 public and private hospitals. The assessment includes document review, interviews of the key informants by structured open-ended questions, and a review of websites of relevant organizations.Results: Drug Regulatory Authority of Pakistan (DRAP) with a national PV center received a 75% overall performance score on IPAT. To be regarded as “minimally functioning,” a country’s PV and drug safety system must meet all core indicators. DRAP scored 80.76% on the core indicators so cannot be deemed functional at this time. The only province with a regional PV center, Punjab, had scored 72.13% on relevant parameters. Despite receiving funding from the Global Fund, none of the National Public Health Programs (PHPs) have PV centers or associated activities. All hospitals except two private hospitals could not qualify the minimum requirements for functional PV. The absence of a legal framework for mandatory ADR reporting, lack of drug information center, budgetary constraints, no active surveillance activities, the nonexistence of pharmacovigilance risk assessment expert committee, and insufficient coordination among stakeholders were identified as major gaps.Conclusion: The results of the study reveal that Pakistan’s PV system is not fully functional at all levels. A two-phased strategy encompassing the non-financial and financial interventions is proposed to improve the PV systems at the national, provincial, PHPs, and hospitals levels.
Comparative Effectiveness and Safety of Low-Dose Oral Anticoagulants in Patients With Atrial Fibrillation
Authors: Perreault Sylvie , Dragomir Alice , Côté Robert , Lenglet Aurélie , de Denus Simon , Dorais Marc , White-Guay Brian , Brophy James , Schnitzer Mireille E. , Dubé Marie-Pierre , Tardif Jean-Claude 
Published: January 2022

Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and safety.Methods: Using administrative data from Quebec province, Canada, we built a cohort of new warfarin or DOAC users discharged from hospital between 2011 and 2017. We determined CHA2DS2-VASc and HAS-BLED scores, and comorbidities for 3-year prior cohort entry. The primary effectiveness endpoint was a composite of ischemic stroke/systemic embolism (SE), and secondary outcomes included a safety composite of major bleeding (MB) events and effectiveness composite (stroke/SE, death) at 1-year follow-up. We contrasted each low-dose DOAC with warfarin or other DOACs as references using inverse probability of treatment weighting to estimate marginal Cox hazard ratios (HRs).Results: The cohort comprised 22,969 patients (mean age: 80–86). We did not find a significant risk reduction for the stroke/SE primary effectiveness endpoint for DOACs vs. warfarin; however, we observed a significantly lower risk for low-dose dabigatran vs. warfarin (HR [95%CI]: 0.59 [0.42–0.81]) for effectiveness composite, mainly due to a lower death rate. The differences in effectiveness and safety composites between low-dose rivaroxaban vs. warfarin were not significant. However, low-dose apixaban had a better safety composite (HR: 0.68 [0.53–0.88]) vs. warfarin. Comparisons of dabigatran vs. apixaban showed a lower risk of stroke/SE (HR: 0.53 [0.30–0.93]) and a 2-fold higher risk of MB. The MB risk was higher for rivaroxaban than for apixaban (HR: 1.58 [1.09–2.29]).Conclusions: The results of this population-based study suggest that low-dose dabigatran has a better effective composite than warfarin. Compared with apixaban, low-dose dabigatran had a better effectiveness composite but a worse safety profile. Low-dose apixaban had a better safety composite than warfarin and other low-dose DOACs. Given that the comparative effectiveness and safety seem to vary from one DOAC to another, pharmacokinetic data for specific populations are now warranted.
Development of IKATP Ion Channel Blockers Targeting Sulfonylurea Resistant Mutant KIR6.2 Based Channels for Treating DEND Syndrome
Authors: Houtman Marien J. C. , Friesacher Theres , Chen Xingyu , Zangerl-Plessl Eva-Maria , Heyden Marcel A. G. van der , Stary-Weinzinger Anna 
Published: January 2022

Introduction: DEND syndrome is a rare channelopathy characterized by a combination of developmental delay, epilepsy and severe neonatal diabetes. Gain of function mutations in the KCNJ11 gene, encoding the KIR6.2 subunit of the IKATP potassium channel, stand at the basis of most forms of DEND syndrome. In a previous search for existing drugs with the potential of targeting Cantú Syndrome, also resulting from increased IKATP, we found a set of candidate drugs that may also possess the potential to target DEND syndrome. In the current work, we combined Molecular Modelling including Molecular Dynamics simulations, with single cell patch clamp electrophysiology, in order to test the effect of selected drug candidates on the KIR6.2 WT and DEND mutant channels.Methods: Molecular dynamics simulations were performed to investigate potential drug binding sites. To conduct in vitro studies, KIR6.2 Q52R and L164P mutants were constructed. Inside/out patch clamp electrophysiology on transiently transfected HEK293T cells was performed for establishing drug-channel inhibition relationships.Results: Molecular Dynamics simulations provided insight in potential channel interaction and shed light on possible mechanisms of action of the tested drug candidates. Effective IKIR6.2/SUR2a inhibition was obtained with the pore-blocker betaxolol (IC50 values 27–37 μM). Levobetaxolol effectively inhibited WT and L164P (IC50 values 22 μM) and Q52R (IC50 55 μM) channels. Of the SUR binding prostaglandin series, travoprost was found to be the best blocker of WT and L164P channels (IC50 2–3 μM), while Q52R inhibition was 15–20% at 10 μM.Conclusion: Our combination of MD and inside-out electrophysiology provides the rationale for drug mediated IKATP inhibition, and will be the basis for 1) screening of additional existing drugs for repurposing to address DEND syndrome, and 2) rationalized medicinal chemistry to improve IKATP inhibitor efficacy and specificity.
Large Time Behavior on the Linear Self-Interacting Diffusion Driven by Sub-Fractional Brownian Motion With Hurst Index Large Than 0.5 I: Self-Repelling Case
Authors: Gao Han , Guo Rui , Jin Yang , Yan Litan 
Published: January 2022

Let SH be a sub-fractional Brownian motion with index 12<H<1. In this paper, we consider the linear self-interacting diffusion driven by SH, which is the solution to the equationdXtH=dStH−θ(∫0tXtH−XsHds)dt+νdt,X0H=0,where θ &lt; 0 and ν∈R are two parameters. Such process XH is called self-repelling and it is an analogue of the linear self-attracting diffusion [Cranston and Le Jan, Math. Ann. 303 (1995), 87–93]. Our main aim is to study the large time behaviors. We show the solution XH diverges to infinity, as t tends to infinity, and obtain the speed at which the process XH diverges to infinity as t tends to infinity.
Compaction Density Evaluation Model of Sand-Gravel Dam Based on Elman Neural Network With Modified Particle Swarm Optimization
Authors: Liu Biao , Zhao Yufei , Wang Wenbo , Liu Biwang 
Published: January 2022

The compaction density of sand-gravel materials has a strong gradation correlation, mainly affected by some material source parameters such as P5 content (material proportion with particle size greater than 5 mm), maximum particle size and curvature coefficient. When evaluating the compaction density of sand-gravel materials, the existing compaction density evaluation models have poor robustness and adaptability because they do not take into full consideration the impact of material source parameters. To overcome the shortcomings of existing compaction density models, this study comprehensively considers the impact of material source parameters and compaction parameters on compaction density. Firstly, asymmetric data were fused and a multi-source heterogeneous dataset was established for compaction density analysis. Then, the Elman neural network optimized by the adaptive simulated annealing particle swarm optimization algorithm was proposed to establish the compaction density evaluation model. Finally, a case study of the Dashimen water conservancy project in China is employed to demonstrate the effectiveness and feasibility of the proposed method. The results show that this model performs high-precision evaluation of the compaction density at any position of the entire working area which can timely correct the weak area of compaction density on the spot, and reduce the number of test pit tests.
Effects of Body-Oriented Interventions on Preschoolers' Social-Emotional Competence: A Systematic Review
Authors: Dias Rodrigues Andreia , Cruz-Ferreira Ana , Marmeleira José , Veiga Guida 
Published: January 2022

Objective:A growing body of evidence supports the effectiveness of body-oriented interventions (BOI) in educational contexts, showing positive influences on social-emotional competence. Nevertheless, there is a lack of systematization of the evidence regarding preschool years. This is a two-part systematic review. In this first part, we aim to examine the effects of BOI on preschoolers' social-emotional competence outcomes.Data Sources:Searches were conducted in Pubmed, Scopus, PsycInfo, ERIC, Web of Science, Portal Regional da BVS and CINAHL.Eligibility Criteria:English, French and Portuguese language articles published between January 2000 and October 2020, that evaluated the effects of BOI implemented in educational contexts on social-emotional competence of preschool children. Only randomized controlled trials (RCT) or quasi-RCT were included.Data Extraction and Synthesis:Two reviewers independently completed data extraction and risk-of-bias assessment. The level of scientific evidence was measured through the Best Evidence Synthesis.Results:Nineteen studies were included. There was strong evidence that BOI do not improve anger/aggression, delay of gratification and altruism. Nevertheless, there was moderate evidence that BOI effectively improve other social-emotional outcomes, such as empathy, social interaction, social independence, general internalizing behaviors, and general externalizing behaviors. The lack of scientific evidence was compromised by the methodological quality of the studies.Conclusion:BOI effectively improve specific social-emotional competences of preschool children.Systematic Review Registration:PROSPERO, identifier CRD42020172248.
Consequences of the COVID-19 Pandemic on Children's Mental Health: A Meta-Analysis
Authors: Bussières Eve-Line , Malboeuf-Hurtubise Catherine , Meilleur A. , Mastine Trinity , Hérault Elodie , Chadi Nicholas , Montreuil Marjorie , Généreux Mélissa , Camden Chantal ,   PRISME-COVID Team
Published: January 2022

Background:The COVID-19 pandemic has exacerbated mental health problems in many individuals, including children. Children with pre-existing socio-demographic or developmental risk factors may be particularly vulnerable to the negative effects of the pandemic and associated public health preventive measures.Objective:This systematic review and meta-analysis explored the impacts of the COVID-19 pandemic on the mental health of children aged 5–13 years-old, while highlighting the specific difficulties experienced by children with neurodevelopmental issues or chronic health conditions.Methods:A systematic search of the published literature was conducted in Medline, ERIC, PsycINFO, and Google Scholar, followed by a quantitative meta-analysis of the eligible studies.Results:Out of the 985 articles identified, 28 empirical studies with prospective or retrospective longitudinal data were included in the quantitative synthesis. COVID-19 lockdown measures were associated with negative general mental health outcomes among children (g= 0.28,p&lt; 0.001, andk= 21), but of small magnitude. Sleep habits were also changed during the pandemic, as sleep duration significantly increased in children (g= 0.32;p= 0.004, andk= 9). Moreover, results did not differ between children from the general population and those from clinical populations such as children with epilepsy, oncology, neurodevelopmental disorders, or obesity. Effect sizes were larger in European vs. Asian countries.Conclusions:Studies included in this review suggest that children's mental health was generally negatively impacted during the COVID-19 pandemic. More research is needed to understand the long-term effects of the COVID-19 pandemic on children's mental health and the influence of specific risks factors as they evolve over time.
Companions in the Abyss: A Feasibility and Acceptability Study of an Online Therapy Group for Healthcare Providers Working During the COVID-19 Pandemic
Authors: Smith-MacDonald Lorraine , Lusk Jaimie , Lee-Baggley Dayna , Bright Katherine , Laidlaw Alexa , Voth Melissa , Spencer Shaylee , Cruikshank Emily , Pike Ashley , Jones Chelsea , Bremault-Phillips Suzette 
Published: January 2022

Introduction:In the context of the global pandemic of the SARS-CoV-2 coronavirus (COVID-19), healthcare providers (HCPs) have experienced difficult moral and ethical dilemmas. Research is highlighting the importance of moral injury (MI)–a trauma syndrome related to transgressing personal morals and values–in understanding the psychological harm and occupational impairment experienced by HCPs. To date, MI treatments have largely been developed for military personnel and veterans and rely on in-person one-on-one psychotherapy.Purpose:This project aims to explore the feasibility and acceptability of an evidence-informed online Acceptance and Commitment Therapy-based group therapy for MI in HCPs called “Accepting Moral Pain and Suffering for Healthcare Providers” (AMPS-HCP).Method:This feasibility and acceptability study included three separate phases with the first two phases focused on the development of the psychotherapeutic intervention and the third phase focused on the evaluation of the psychotherapeutic intervention. Eight participants (including registered nurses, practical nurses and respiratory therapists) completed seven 90-min sessions in an online group format. The focus of these sessions included ACT and MI psychoeducation and experientials. Qualitative semi-structured interview data was thematically analyzed while demographic and quantitative self-reported outcome data underwent descriptive analysis and non-parametric testing.Results:Results show that the intervention was highly feasible and acceptable to healthcare providers who worked on the frontline during COVID-19. Feasibility (referrals, eligibility, retention, participation engagement) was strong (8 out of 10 participants; 80% vs. desired &gt;70% eligibility) and overall, 80% of participants completed 71% of the intervention. Data further supported the applicability and acceptability of the intervention. Preliminary data suggests that AMPS-HCP may supports HCPs to address MI.Discussion:This study is the first to report on the development and evaluation of an online MI group intervention for registered nurses, registered practical nurses, and respiratory therapists working during COVID-19. Results showed the use of both the online and group components of the intervention were acceptable and feasible during the third wave of COVID-19.
Identification of Children of Mentally Ill Patients and Provision of Support According to the Norwegian Health Legislation: A 11-Year Review
Authors: Reedtz Charlotte , Jensaas Eva , Storjord Trine , Kristensen Kjersti Bergum , Lauritzen Camilla 
Published: January 2022

Background:According to amended legislation implemented in Norway in 2010, personnel in healthcare services for adults are obligated to identify patients' minor children and to assess the family situation. Health personnel is also obligated to contribute to adequate support to families affected by parental mental illness or substance use disorders. The intention behind the amendment was to support and protect children of mentally ill parents, as they are at risk of developing problems of their own. The aim of the present study was to evaluate health personnel's practice during the years 2010-2020, more specifically; (a) to what extent children of patients with mental illness and substance use disorders are registered in patient records, and (b) to what extent activities relating to the assessment and support of patients' minor children are documented in patient records.Method:The participants in the study are patients admitted to Division for Mental Health and Substance Use at the University Hospital of North Norway in the years 2010–2020. The data was drawn from patient records during October 2021.Results:The registration of patients' minor children is considerably strengthened since the introduction of the new Norwegian Health Personnel Act in 2010, and estimates show that 56% of patients' minor children are identified. However, only 31% of cases where patients have identified minor children this result in health personnel performing activities to support the children.Discussion:Based on the rising proportion of identified minor children throughout the 10-year period, it seems evident that the dissemination efforts have contributed to the development of some new skills among health personnel. However, compared with the national estimation that 35% of mentally ill and substance abusing patients have minor children, a large proportion of children remains unidentified. After identification, there seem to still be a long way to go before minor children are systematically offered support. Different solutions to strengthen the implementation of new skills in clinical practice, to ensure the identification of minor children and provision of necessary support for them is discussed.
EHealth and Its Role in Supporting Audiological Rehabilitation: Patient Perspectives on Barriers and Facilitators of Using a Personal Hearing Support System With Mobile Application as Part of the EVOTION Study
Authors: Murdin Louisa , Sladen Mark , Williams Hannah , Bamiou Doris-Eva , Bibas Athanasios , Kikidis Dimitris , Oiknonomou Apostolis , Kouris Ioannis , Koutsouris Dimitris , Pontoppidan Niels H. 
Published: January 2022

BackgroundHearing loss is a major public health challenge. Audiology services need to utilise a range of rehabilitative services and maximise innovative practice afforded by technology to actively promote personalized, participatory, preventative and predictive care if they are to cope with the social and economic burden placed on the population by the rapidly rising prevalence of hearing loss. Digital interventions and teleaudiology could be a key part of providing high quality, cost-effective, patient-centred management. There is currently very limited evidence that assesses the hearing impaired patient perspective on the acceptance and usability of this type of technology.AimThis study aims to identify patient perceptions of the use of a hearing support system including a mobile smartphone app when used with Bluetooth-connected hearing aids across the everyday life of users, as part of the EVOTION project.MethodsWe applied a questionnaire to 564 participants in three countries across Europe and analysed the following topics: connectivity, hearing aid controls, instructional videos, audiological tests and auditory training.Key FindingsOlder users were just as satisfied as younger users when operating this type of technology. Technical problems such as Bluetooth connectivity need to be minimised as this issue is highly critical for user satisfaction, engagement and uptake. A system that promotes user-controllability of hearing aids that is more accessible and easier to use is highly valued. Participants are happy to utilise monitoring tests and auditory training on a mobile phone out of the clinic but in order to have value the test battery needs to be relevant and tailored to each user, easy to understand and use. Such functions can elicit a negative as well as positive experience for each user.ConclusionOlder and younger adults can utilise an eHealth mobile app to complement their rehabilitation and health care. If the technology works well, is tailored to the individual and in-depth personalised guidance and support is provided, it could assist maximisation of hearing aid uptake, promotion of self-management and improving outcomes.
Control of the Longitudinal Compression and Transverse Focus of Ultrafast Electron Beam for Detecting the Transient Evolution of Materials
Authors: Cai Xintian , Wang Zhen , Ji Chaoyue , Wang Xuan , Gan Zhiyin , Liu Sheng 
Published: January 2022

Ultrafast detection is an effective method to reveal the transient evolution mechanism of materials. Compared with ultra-fast X-ray diffraction (XRD), the ultra-fast electron beam is increasingly adopted because the larger scattering cross-section is less harmful to the sample. The keV single-shot ultra-fast electron imaging system has been widely used with its compact structure and easy integration. To achieve both the single pulse imaging and the ultra-high temporal resolution, magnetic lenses are typically used for transverse focus to increase signal strength, while radio frequency (RF) cavities are generally utilized for longitudinal compression to improve temporal resolution. However, the detection signal is relatively weak due to the Coulomb force between electrons. Moreover, the effect of RF compression on the transverse focus is usually ignored. We established a particle tracking model to simulate the electron pulse propagation based on the 1-D fluid equation and the 2-D mean-field equation. Under considering the relativity effect and Coulomb force, the impact of RF compression on the transverse focus was studied by solving the fifth-order Rung–Kutta equation. The results show that the RF cavity is not only a key component of longitudinal compression but also affects the transverse focusing. While the effect of transverse focus on longitudinal duration is negligible. By adjusting the position and compression strength of the RF cavity, the beam spot radius can be reduced from 100 μm to 30 μm under the simulation conditions in this paper. When the number of single pulse electrons remains constant, the electrons density incident on the sample could be increased from 3.18×1012 m−2 to 3.54×1013 m−2, which is 11 times the original. The larger the electron density incident on the sample, the greater the signal intensity, which is more conducive to detecting the transient evolution of the material.