bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change of peripapillary retinal nerve fiber layer and choroidal thickness during 4-year myopic progress: Boramae Myopia Cohort Study Report 4
Authors: Kim Martha , Lee Kyoung Min , Choung Ho-Kyung , Oh Sohee , Kim Seok Hwan 
Published: April 2022

AimsTo investigate the longitudinal changes of peripapillary retinal nerve fibre layer (RNFL) and choroidal thickness during myopic axial elongation.MethodsPeripapillary RNFL and choroidal thickness were prospectively evaluated by spectral-domain optical coherence tomography (SD-OCT) in 46 eyes of 23 myopic children over the course of 4 years. Using serial OCT images acquired based on a fixed scan circle in the glaucoma progression analysis mode, general and sectoral RNFL thicknesses were acquired at the same position and the angular location of the peak was measured. The peripapillary choroidal thickness likewise was measured at eight positions in serial OCT images.ResultsThe mean age at the baseline was 9.6±1.7 years. The mean axial length increased from 24.80±1.28 mm to 25.64±1.35 mm. The global peripapillary RNFL thickness was 98.54±12.06 µm at baseline. The global and sectoral RNFL thicknesses did not change during the 4 years. The angular location of RNFL peaks was also stable and was located in the superotemporal (64.18±10.85°) and inferotemporal (293.98±11.62°) sectors. The global peripapillary choroidal thickness was 145.40±28.67 µm at the baseline. The global and sectoral choroidal thicknesses did not change during the 4 years.ConclusionsThe peripapillary RNFL and choroidal thicknesses as well as the locations of the RNFL peaks had been preserved, during the 4-year follow-up on myopic children, when traced and measured from the same location.
Heterozygous variants c.781G>A and c.1066dup ofserine protease 56cause familial nanophthalmos by impairing serine-type endopeptidase activity
Authors: Wu Wei , Xu Jingjie , Yin Houfa , Fu Chenxi , Yao Ke , Chen Xiangjun 
Published: April 2022

Background/aimsNanophthalmos is a rare developmental, bilateral, sporadic or hereditary form of microphthalmos. In this study, the heterozygous variants c.781G>A and c.1066dup of thePRSS56gene were identified in two patients with nanophthalmos. This study reports the clinical manifestation and the underlying pathogenic mechanism.MethodsWhole-exome sequencing was performed to identify the pathogenic genes in a Chinese family with nanophthalmos. The molecular simulation was used to predict the structures of wild-type or mutant PRSS56. The PRSS56 wild-type or mutation overexpression cellular models have been constructed accordingly. The subcellular localisation was then observed using immunofluorescence and Western-blot techniques. The Folin-Ciocalteu assay was carried out to evaluate serine-type endopeptidase activity, and a wound-healing assay was used to examine the cellular migratory ability.ResultsThe whole-exome sequencing revealed that heterozygous variants c.781G>A and c.1066dup of thePRSS56gene might contribute to nanophthalmos. Both variants were not identified in the dbSNP, 1000 Genome project or ESP6500 databases. Furthermore, the variants were highly conserved and were involved in biological functions. The mutations result in destructive protein structure and impede serine-type endopeptidase activity, thereby impairing subcellular localisation and cellular migration.ConclusionThe c.781G>A and c.1066dup variants of thePRSS56 genemight negatively affect protein structures, subcellular localisation, serine-type endopeptidase activity and cellular migratory ability. Together, these changes could lead to the development of nanophthalmos. This study identifies the PRSS56 gene as a potential target for nanophthalmos diagnosis and treatment.
Prognosis and antiplatelet therapy of small single subcortical infarcts in penetrating artery territory: a post hoc analysis of the Third China National Stroke Registry
Authors: Xu Yu-Yuan , Jing Jing , Zhang Yi-Jun , Wang An-Xin , Li Zi-Xiao , Liu Li-Ping , Zhao Xing-Quan , Wang Yi-Long , Li Hao , Meng Xia , Wang Yong-Jun 
Published: April 2022

BackgroundSmall single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.MethodsWe prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.ResultsAmong 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p<0.0001) and 1 year (OR 2.054, 95% CI 1.561 to 2.702; p<0.0001), as well as composite vascular events at 3 months (OR 2.306, 95% CI 1.674 to 3.178; p<0.0001) and 1 year (OR 1.983, 95% CI 1.530 to 2.570; p<0.0001), compared with the non-PAS group. In both groups, dual antiplatelet therapy was not superior to single antiplatelet therapy in preventing stroke recurrence, composite vascular events and disability.ConclusionPAS related to significantly higher rates of short-term and long-term stroke recurrence and composite vascular events, suggesting heterogeneous mechanisms in SSSI subgroups. The effectiveness of antiplatelet therapy for SSSI needs further investigation.
Identifying and understanding the factors that influence the functioning of integrated healthcare systems in the NHS: a systematic literature review
Authors: Bhat Karthik , Easwarathasan Rokshan , Jacob Milan , Poole William , Sapaetharan Vithullan , Sidhu Manu , Thomas Ashvin 
Published: April 2022

ObjectivesThe National Health Service has been moving towards integrated care for the best part of two decades to address the growing financial and service pressures created by an ageing population. Integrated healthcare systems (IHSs) join up health and social care services and have been established to manage the care of individuals with complex chronic conditions but with varied success. It is therefore imperative to conduct a Systematic Literature Review (SLR) to identify and understand the factors that influence their successful functioning, and ascertain the factor with the greatest influence, in order to ensure positive outcomes when establishing future IHSs.MethodsArticles published between 1 January 1997 and 8 March 2020 were analysed from the following six databases: Healthcare Management Information Consortium, Nuffield Trust, Cumulative Index to Nursing and Allied Health Literature, PubMed, National Institute for Health and Care Excellence Evidence and Health Systems Evidence. Those deemed relevant after title and abstract screening were procured for subsequent review of the full-text article.ResultsThirty-three finalised articles were analysed in this SLR to provide a comprehensive overview of the factors that influence the functioning of IHSs. Factors were stratified into six key categories: organisational culture, workforce management, interorganisational collaboration, leadership ability of staff, economic factors and political factors. Leadership was deemed to be the most influential factor due to its intrinsic and instrumental role in influencing the other key factors.ConclusionsThe findings of this SLR may serve as a guide to developing tailor-made recommendations and policies that address the identified key factors and thereby improve the functioning of present and future IHSs. Furthermore, due to both its overarching influence and the inadequacy of literature in this field, there is a strong case for further research exploring leadership development specifically for IHSs.
Was there an improvement in the years of life lost (YLLs) for non-communicable diseases in the Soma and Minamisoma cities of Fukushima after the 2011 disaster? A longitudinal study
Authors: Ono Kyoko , Murakami Michio , Tsubokura Masaharu 
Published: April 2022

ObjectivesThis study aimed to determine cause-specific years of life lost (YLL) changes between predisaster and postdisaster in disaster-affected municipalities, compared with the national average. We estimated the YLL in Soma and Minamisoma cities (the subject area) in Fukushima, Japan, where the tsunami and the nuclear accident hit in 2011.ParticipantsWe used vital registration records from a national survey conducted between January 2006 and December 2015. We analysed 6369 death data in the predisaster period (2006–2010) and 6258 death data in the postdisaster period (2011–2015).MethodsWe incorporated vital statistics data as follows: age-based, sex-based and International Classification of Diseases, 10th Revision-based cause-specific deaths and calculated YLLs by ages 0, 40, 65 and 75 and sex for attributable causes of death for heart diseases, cerebrovascular diseases, pneumonia, all cancers and specific cancers; breast cancer, colorectal cancer, leukaemia, lung cancer, stomach cancer and uterine cancer for predisaster and postdisaster in the subject area.ResultsYLL attributed to heart diseases for males showed no decrease and YLL postdisaster was 0.37 years larger than that of the national average at age 0. The difference was −0.17 (95% uncertainty interval: −0.40 to 0.05) years at age 65. It decreased for females; the difference was 0.37 (0.18–0.57) years after the disaster. YLL decrease (that is, difference) in cerebrovascular diseases at age 0 was 0.27 (0.09–0.44) years and 0.18 (0.04–0.32) years; however, the YLLs postdisaster were still 0.24 and 0.25 years larger than those for the national average for males and females, respectively. YLL attributed to cancer did not increase even after the nuclear disaster.ConclusionsWe specified the causes of death to be reduced in disaster-affected areas in the future. This study emphasised the importance of understanding how the health situation changed for the whole society of the area from a comprehensive perspective, rather than focusing only on small mortality increases.
Evaluating antibiotic stewardship and healthcare-associated infections surveillance assisted by computer: protocol for an interrupted time series study
Authors: Baudet Alexandre , Agrinier Nelly , Charmillon Alexandre , Pulcini Céline , Lozniewski Alain , Aissa Nejla , Lizon Julie , Thilly Nathalie , Demoré Béatrice , Florentin Arnaud 
Published: April 2022

IntroductionAntibiotic resistance is one of the most pressing health threats that mankind faces now and in the coming decades. Antibiotic resistance leads to longer hospital stays, higher medical costs and increased mortality. In order to tackle antibiotic resistance, we will implement in our tertiary care university hospital a computerised-decision support system (CDSS) facilitating antibiotic stewardship and an electronic surveillance software (ESS) facilitating infection prevention and control activities. We describe the protocol to evaluate the impact of the CDSS/ESS combination in adult inpatients.Methods and analysisWe conduct a pragmatic, prospective, single-centre, before–after uncontrolled study with an interrupted time-series analysis 12 months before and 12 months after the introduction of the CDSS for antibiotic stewardship (APSS) and ESS for infection surveillance (ZINC). APSS and ZINC will assist, respectively, the antibiotic stewardship and the infection prevention and control teams of Nancy University Hospital (France). We will evaluate the impact of the CDSS/ESS on the antibiotic use in adult (≥18 years) inpatients (hospitalised ≥48 hours). The primary outcome is the prescription rate by all healthcare professionals from the hospital of all systemic antibiotics expressed in defined daily doses/1000 patients/month. Concurrently, we will assess the safety of the intervention, its impact on the appropriateness of antibiotic prescriptions and on additional precautions (isolation precautions) as recommended in guidelines, and on bacterial epidemiology (multidrug-resistant bacteria and Clostridioides difficile infections) in the hospital. Finally, we will evaluate the users’ satisfaction and the cost of this intervention from the hospital perspective.Ethics and disseminationThe protocol has been approved by the Ethics Committee of Nancy University Hospital and registered on the ClinicalTrials platform. Results will be disseminated through conferences’ presentations and publications in peer-reviewed journals.Trial registration numberNCT04976829.
Intravenous ketorolac versus morphine in children presenting with suspected appendicitis: a pilot single-centre non-inferiority randomised controlled trial
Authors: Eltorki Mohamed , Busse Jason W , Freedman Stephen B , Thompson Graham , Beattie Karen , Serbanescu Claudiu , Carciumaru Redjana , Thabane Lehana , Ali Samina 
Published: April 2022

ObjectivesDespite a lack of evidence demonstrating superiority to non-steroidal anti-inflammatory drugs, like ketorolac, that are associated with lower risk of harms, opioids remain the most prescribed analgesic for acute abdominal pain. In this pilot trial, we will assess the feasibility of a definitive trial comparing ketorolac with morphine in children with suspected appendicitis. We hypothesise that our study will be feasible based on a 40% consent rate.Methods and analysisA single-centre, non-inferiority, blinded (participant, clinician, investigators and outcome assessors), double-dummy randomised controlled trial of children aged 6–17 years presenting to a paediatric emergency department with ≤5 days of moderate to severe abdominal pain (≥5 on a Verbal Numerical Rating Scale) and are investigated for appendicitis. We will use variable randomised blocks of 4–6 and allocate participants in 1:1 ratio to receive either intravenous (IV) ketorolac 0.5 mg/kg+IV morphine placebo or IV morphine 0.1 mg/kg+IV ketorolac placebo. Analgesic co-intervention will be limited to acetaminophen (commonly used as first-line therapy). Participants in both groups will be allowed rescue therapy (morphine 0.5 mg/kg) within 60 min of our intervention. Our primary feasibility outcome is the proportion of eligible patients approached who provide informed consent and are enrolled in our trial. Our threshold for feasibility will be to achieve a ≥40% consent rate, and we will enrol 100 participants into our pilot trial.Ethics and disseminationOur study has received full approval by the Hamilton integrated Research Ethics Board. We will disseminate our study findings at national and international paediatric research conferences to garner interest and engage sites for a future multicentre definitive trial.Trial registrationNCT04528563, Pre-results.
Exploring how and why social prescribing evaluations work: a realist review
Authors: Elliott Megan , Davies Mark , Davies Julie , Wallace Carolyn 
Published: April 2022

ObjectiveThe evidence base for social prescribing is inconclusive, and evaluations have been criticised for lacking rigour. This realist review sought to understand how and why social prescribing evaluations work or do not work. Findings from this review will contribute to the development of an evidence-based evaluation framework and reporting standards for social prescribing.DesignA realist review.Data sourcesASSIA, CINAHL, Embase, Medline, PsycINFO, PubMed, Scopus Online, Social Care Online, Web of Science and grey literature.Eligibility criteriaDocuments reporting on social prescribing evaluations using any methods, published between 1998 and 2020 were included. Documents not reporting findings or lacking detail on methods for data collection and outcomes were excluded.AnalysisIncluded documents were segregated into subcases based on methodology. Data relating to context, mechanisms and outcomes and the programme theory were extracted and context-mechanism-outcome configurations were developed. Meta-inferences were drawn from all subcases to refine the programme theory.Results83 documents contributed to analysis. Generally, studies lacked in-depth descriptions of the methods and evaluation processes employed. A cyclical process of social prescribing evaluation was identified, involving preparation, conducting the study and interpretation. The analysis found that coproduction, alignment, research agency, sequential mixed-methods design and integration of findings all contributed to the development of an acceptable, high-quality social prescribing evaluation design. Context-mechanism-outcome configurations relating to these themes are reported.ConclusionsTo develop the social prescribing evidence base and address gaps in our knowledge about the impact of social prescribing and how it works, evaluations must be high quality and acceptable to stakeholders. Development of an evaluation framework and reporting standards drawing on the findings of this realist review will support this aim.PROSPERO registration numberCRD42020183065.
Assessing the cost-effectiveness of precision medicine: protocol for a systematic review and meta-analysis
Authors: Chen Wenjia , Anothaisintawee Thunyarat , Butani Dimple , Wang Yi , Zemlyanska Yaroslava , Wong Chong Boon Nigel , Virabhak Suchin , Hrishikesh M A , Teerawattananon Yot 
Published: April 2022

IntroductionPrecision medicine (PM) involves gene testing to identify disease risk, enable early diagnosis or guide therapeutic choice, and targeted gene therapy. We aim to perform a systematic review and meta-analysis to quantify the cost-effectiveness profile of PM stratified by intervention type, identify sources of heterogeneity in the value-for-money of PM.Methods and analysisWe will perform a systematic search in Embase, MEDLINE, EconLit and CRD databases for studies published in English language or with translation in English between 1 January 2011 and 8 July 2021 on the topic of cost-effectiveness analysis of PM interventions. The focus will be on studies that reported health and economic outcomes. Study quality will be assessed using the Biases in Economic Studies checklist. The incremental net benefit of PM screening, diagnostic, treatment-targeting and therapeutic interventions over conventional strategies will be respectively pooled across studies using a random-effect model if heterogeneity is present, otherwise a fixed-effect model. Subgroup analyses will be performed based on disease area, WHO region and World Bank country-income level. Additionally, we will identify the potential sources of heterogeneity with random-effect meta-regressions. Finally, biases will be detected using jackknife sensitivity analysis, funnel plot assessment and Egger’s tests.Ethics and disseminationFor this type of study ethics approval or formal consent is not required. The results will be disseminated at various presentations and feedback sessions, in conference abstracts and manuscripts that will be submitted to peer-reviewed journals.PROSPERO registration numberCRD42021272956.
Maintenance of physical activity after cardiac rehabilitation (FAIR): study protocol for a feasibility trial
Authors: Andersen Rune Martens , Skou Søren Thorgaard , Clausen Mikkel Bek , Jäger Madalina , Zangger Graziella , Grøntved Anders , Brønd Jan Christian , Soja Anne Merete Boas , Tang Lars H 
Published: April 2022

IntroductionTo enhance health and prevent secondary consequences for patients with cardiovascular disease (CVD), maintenance of an active lifestyle following participation in cardiac rehabilitation (CR) is important. However, levels of physical activity often decrease after completion of a structured CR programme. Models that support long-term behaviour change with a sustained level of physical activity are imperative. The aim of this study is to evaluate the feasibility of a mobile health intervention based on the Health Action Process Approach theoretical model of behaviour change in patients with CVD for 3 months after completion of a CR programme.Methods and analysisIn a feasibility trial design, we will recruit 40 participants from CR programmes at Slagelse Hospital, the City of Slagelse (municipality), or Holbæk Hospital. After completing the standard structured CR programme, each participant will create an action plan for physical activity together with a physiotherapist. Following that, participants are sent 2 weekly text messages for 3 months. The first text message prompts physical activity, and the second will check if the action plan has been followed. If requested by participants, a coordinator will call and guide the physical activities behaviour. The feasibility of this maintenance intervention is evaluated based on predefined progression criteria. Physical activity is measured with accelerometers at baseline and at 3 months follow-up.Ethics and disseminationStudy approval was waived (EMN-2021-00020) by the Research Ethics Committee of Region Zealand, Denmark. Study results will be made public and findings disseminated to patients, health professionals, decision-makers, researchers and the public.Trial registration numberNCT05011994.
Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway
Authors: Wang Fei , Xia Jian-jun , Shen Li-juan , Jiang Ting-ting , Li Wu-lin , You Da-li , Chang Qing , Hu Shan-you , Wang Li , Wu Xiao 
Published: April 2022

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.