bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit
Authors: Bhatt Reena , Madsen Jens , Castillo-Hernandez Tania , Chant Kathy , Dehbi Hakim-Moulay , Marlow Neil , Clark Howard 
Published: August 2024

IntroductionChronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory illness are characterised by rapid consumption of endogenous surfactant and slow replenishment. Exogenous surfactant is routinely administered to infants born before 28 weeks of gestation as prophylaxis. Endogenous surfactant includes four proteins, known as surfactant proteins (SPs) A, B, C and D. Current bovine-derived and porcine-derived surfactant preparations only contain SPs B and C. SP-D has a key role in lung immune homeostasis as part of the innate immune system. Laboratory studies using recombinant SP-D have demonstrated reduced inflammation, which may be a pathway to reducing the associated morbidity from BPD. RESPONSE uses a recombinant fragment of human SP D (rfhSP-D), in a phase I safety and dose-escalation trial as the first stage in determining its effect in humans.Methods and analysisThis is a single-centre, dose-escalation, phase I safety study aiming to recruit 24 infants born before 30 weeks gestation with respiratory distress syndrome. In addition to routine surfactant replacement therapy, participants will receive three doses of rfhSP-D via endotracheal route at either 1 mg/kg, 2 mg/kg or 4 mg/kg. The study uses a Bayesian continual reassessment method to make dose escalation decisions. Dose-limiting events (DLE) in this trial will be graded according to the published Neonatal Adverse Event Severity Score. The primary outcome of this study is to evaluate the safety profile of rfhSP-D across each dose level based on the profile of DLE to establish the recommended phase 2 dose (RP2D) of rfhSP-D.Ethics and disseminationThe RESPONSE study has received ethical approval from London-Brent NHS Research Health Authority ethics committee. Results from the study will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numbersISRCTN17083028,NCT05898633.Protocol versionRESPONSE Protocol V.4.0 24th July 2024.
Economic evaluations of pancreatic cancer screening: a systematic review protocol
Authors: Wittram Robert , König Hans-Helmut , Brettschneider Christian 
Published: August 2024

IntroductionThe early detection of pancreatic cancer is an important step in reducing mortality by offering patients curative treatment. Screening strategies in risk populations and by means of different detection methods have been economically evaluated. However, a synthesis of screening studies to inform resource allocation towards early detection within the disease area has not been done. Therefore, studies evaluating the cost-effectiveness and costs of screening for pancreatic cancer should be systematically reviewed.Methods and analysisA systematic review of economic evaluations reporting the cost-effectiveness or costs of pancreatic cancer screening will be conducted. The electronic databases Medline, Web of Science and EconLit will be searched without geographical or time restrictions. Two independent reviewers will select eligible studies based on predefined criteria. The study quality will be assessed using the Consolidated Health Economic Evaluation Reporting Standards statement and the Bias in Economic Evaluation checklist. One reviewer will extract relevant data and a second reviewer will cross-check compliance with the extraction sheet. Key items will include characteristics of screened individuals, the screening strategies used, and costs, health effects and cost-effectiveness as study outputs. Differences of opinion between the reviewers will be solved by consulting a third reviewer.Ethics and disseminationEthics approval is not required for this study since no original data will be collected. The results will be disseminated through presentations at conferences and publication in a peer-reviewed journal. The results of the systematic review will inform future economic evaluations of pancreatic screening, which provide guidance for decision-making in healthcare resource prioritisation.PROSPERO registration numberCRD42023475348.
Study protocol of a sequential, multiple assignment, randomised trial using an adaptive intervention to reduce loneliness among Chinese older adults in Hong Kong
Authors: Tang Vivien Foong Yee , Jiang Da , Kwok Jojo Yan Yan , Qian Min , Yeung Dannii Yuen-lan , Chow Esther Oi Wah , Choi Namkee G , Chou Kee Lee 
Published: August 2024

BackgroundLoneliness is a prevalent and alarming issue among older adults that requires effective interventions. While randomised controlled trials have been commonly undertaken to explore reduction in loneliness, there is a growing recognition that a comprehensive treatment strategy involving multiple interventions may yield better outcomes. Therefore, this study aims to develop and identify a two-stage adaptive intervention that combines telephone-delivered behavioural activation (Tele-BA) and mindfulness techniques (Tele-MF) to reduce loneliness in older adults in Hong Kong.MethodsA Sequential, Multiple Assignment, Randomised Trial (SMART) design will be adopted. 244 lonely older adults will be recruited from the community and randomly assigned to either one of the 4-week two-stage, embedded adaptive interventions involving different sequences and dosages of Tele-BA and Tele-MF (eg, 4 weeks of Tele-BA followed by booster sessions for responders or 4 weeks of Tele-BA followed by 4 weeks of Tele-BA with motivational component or 4 weeks of Tele-MF for non-responders) based on a set of decision rules. The primary outcome will be loneliness measured by the Revised University of California Los Angeles (UCLA) Loneliness Scale. Secondary outcomes, such as De Jong Gierveld Loneliness Scale, perceived stress, sleep quality and depressive and anxiety symptoms, will be assessed. Adhering to the intention-to-treat principles, the data will be analysed using linear mixed models. The findings may have implications for the development of psychosocial adaptive interventions involving BA and MF to reduce loneliness and improve well-being among older adults in Hong Kong using the SMART design.Ethics and disseminationEthical approval was obtained by the Human Research Ethics Committee at The Education University of Hong Kong (reference: 2022-2023-0117). The findings from this study will be presented in academic conferences and submitted for publication.Trial registration numberChiCTR2300077472.
Factors influencing the reliability of measurements in eyes with full-thickness macular holes: are we measuring incorrectly?
Authors: Moussa George , Jalil Assad , Lippera Myrta , Alnafisee Nouf , Ivanova Tsveta 
Published: August 2024

PurposeThe calliper function is used for manual measurements of full thickness macular holes (FTMHs). We aimed to investigate whether a reproducible difference could be detected beyond interobserver variability between two commonly used manufacturers in their manual calliper facility in spectral domain optical coherence tomography (OCT) for metrics related to FTMH.MethodsThis is a non-interventional, retrospective, observational study. Two independent observers examined 8 eyes (16 OCT) scans and 128 measurements (minimal linear diameter (MLD), basal diameter and hole height on both sides) of FTMHs, taken on Heidelberg Spectralis and Topcon Triton (OCT machines). The interobserver agreement and OCT machine agreement of measurements were analysed by Bland-Altman plots and intraclass correlation coefficient (ICC) analysis. Spectralis and Triton had 125 µm and 50 µm horizontal b-scan spacing, respectively.ResultsOverall, we report high absolute agreement in interobserver (ICC 0.991 (95% CI 0.985 to 0.995, p<0.001)) and OCT machine (ICC 0.993 (95% CI 0.987 to 0.996, p<0.001)) variability. Lower horizontal resolution in Triton compared with Spectralis leads to interobserver variability, in smaller horizontal measurements. Lower horizontal scanning density in Spectralis lead to relatively large interobserver variation if different reference scans were chosen, and consistently smaller MLD measurements than Triton. Vertical measurements without 1:1 scaling lead to inaccurate exaggerated oblique vertical measurements. Calliper function appears otherwise identically calibrated.ConclusionsWe report excellent interobserver and OCT machine agreement in measurements. However, the paper shows several factors that could influence the reliability of measurements acquired in eyes with FTMHs, such as the dimension of the hole as well as different image resolution, density scanning protocols or vertical scaling of the OCT machines viewing platform.
Improvement of temperature surveillance of neonates in low-resource settings by a simple low-cost device: a descriptive study
Authors: Garvs Janneke , Genzel-Boroviczény Orsolya , Phiri Ajib , Schultz Andreas 
Published: August 2024

IntroductionNeonatal hypothermia in low-resource settings is prevalent and closely associated with high morbidity and mortality. We examined if an easy-to-read temperature detector device improves health outcomes.MethodsIn a descriptive study, 1009 admissions to a neonatal ward in a tertiary care hospital in Lilongwe, Malawi, were analysed and divided into a baseline and a trial group. The data of 531 newborns with standard care (SC) before the trial were compared with 478 newborns during the implementation of the device (device care=DC). Staff and caregivers were trained on using the device and how to react in case of hypothermia. Data were collected from patient files, device documentation sheets, interviews and focus group discussions. Hypothermia was defined as a body temperature <36.5°C.ResultsDuring the trial, body temperatures throughout the hospital stay were significantly more often obtained (p<0.0001). The median temperature measurements per newborn per day were 1.3 times with SC and 1.6 times with DC, and mild hypothermia was more frequently detected. Moderate hypothermia was avoided in the lightest weight group possibly contributing to significantly shorter hospital stays of surviving newborns (p=0.007). Many caregivers had difficulties using and interpreting the device correctly, and 47% of the reported colours did not match the registered temperatures. Contrary to the above, a questionnaire and focus group discussions with caregivers and health workers showed a high acceptance and the overall opinion that the device was beneficial.ConclusionWith more frequent temperature checks, infants with lower birth weight possibly benefited from implementing an easy-to-read continuous temperature indicator, but hypothermia rates remained high. Our data and experiences reveal structural, communicational and consistency/interpretation deficits. Although specifically designed for low-resource settings, the implementation of the device needs a well-working and structured environment, especially regarding staff and caregiver communication.
What influences ambulance clinician decisions to pre-alert emergency departments: a qualitative exploration of pre-alert practice in UK ambulance services and emergency departments
Authors: O'Hara Rachel , Sampson Fiona C , Long Jaqui , Coster Joanne , Pilbery Richard 
Published: August 2024

BackgroundAmbulance clinicians use pre-alerts to inform receiving hospitals of the imminent arrival of a time-critical patient considered to require immediate attention, enabling the receiving emergency department (ED) or other clinical area to prepare. Pre-alerts are key to ensuring immediate access to appropriate care, but unnecessary pre-alerts can divert resources from other patients and fuel ‘pre-alert fatigue’ among ED staff. This research aims to provide a better understanding of pre-alert decision-making practice.MethodsSemi-structured interviews were conducted with 34 ambulance clinicians from three ambulance services and 40 ED staff from six receiving EDs. Observation (162 hours) of responses to pre-alerts (n=143, call-to-handover) was also conducted in the six EDs. Interview transcripts and observation notes were imported into NVIVO and analysed using thematic analysis.FindingsPre-alert decisions involve rapid assessment of clinical risk based on physiological observations, clinical judgement and perceived risk of deterioration, with reference to pre-alert guidance. Clinical experience (pattern recognition and intuition) and confidence helped ambulance clinicians to understand which patients required immediate ED care on arrival or were at highest risk of deterioration. Ambulance clinicians primarily learnt to pre-alert ‘on the job’ and via informal feedback mechanisms, including the ED response to previous pre-alerts. Availability and access to clinical decision support was variable, and clinicians balanced the use of guidance and protocols with concerns about retention of clinical judgement and autonomy. Differences in pre-alert criteria between ambulance services and EDs created difficulties in deciding whether to pre-alert and was particularly challenging for less experienced clinicians.ConclusionWe identified potentially avoidable variation in decision-making, which has implications for patient care and emergency care resources, and can create tension between the services. Consistency in practice may be improved by greater standardisation of guidance and protocols, training and access to performance feedback and cross-service collaboration to minimise potential sources of tension.
Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis
Authors: Shiha Mohamed G , Schiepatti Annalisa , Maimaris Stiliano , Nandi NIcoletta , Penny Hugo A , Sanders David S 
Published: August 2024

ObjectivePotential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD.DesignWe searched Medline, Embase, Scopus and Cochrane Library from 1991 through May 2024 to identify studies evaluating the clinical outcomes of patients with PCD. The progression rates to villous atrophy, seroconversion and response to a gluten-free diet (GFD) were analysed. A random-effect meta-analysis was performed, and the results were reported as pooled proportions with 95% CIs.ResultsSeventeen studies comprising 1010 patients with PCD were included in the final analyses. The pooled prevalence of PCD among patients with suspected coeliac disease was 16% (95% CI 10% to 22%). The duration of follow-up in most of the studies was at least 1 year, with follow-up periods within individual studies ranging from 5 months to 13 years. During follow-up, 33% (95% CI 18% to 48%; I2=96.4%) of patients with PCD on a gluten-containing diet developed villous atrophy, and 33% (95% CI 17% to 48%; I2=93.0%) had normalisation of serology. Among those who adhered to a GFD, 88% (95% CI 79% to 97%; I2=93.2%) reported symptomatic improvement.ConclusionAlmost a third of patients with PCD develop villous atrophy over time, whereas a similar proportion experience normalisation of serology despite a gluten-containing diet. Most symptomatic patients benefit from a GFD. These findings highlight the importance of structured follow-up and individualised management for patients with PCD.
Molecular confirmation that fibrocartilaginous dysplasia is a variant of fibrous dysplasia
Authors: Zhou Juan , Su Xuling , Hu Dingjun , Zhang Li , Chen Chunyan , Sun Keyang , Zhang Huizhen , Liu Zhiyan 
Published: August 2024

AimsFibrocartilaginous dysplasia (FCD) is a subvariant of fibrous dysplasia (FD). This study aims to retrospectively elucidate the clinicopathological and separate genetic features of the cartilaginous and fibro-osseous components of FCD.MethodsIn total, 24 patients (14 men and 10 women) with FCD were included in our cohort. The diagnosis was confirmed morphologically and immunohistochemically, and genetic features were determined via Sanger sequencing.ResultsFive patients were polyostotic, and 19 were monostotic, predominantly concerning the femur. Radiography revealed a well-demarcated ground glass appearance with ring-like or scattered calcification. Histologically, the lesions were characterised by proliferative fibroblasts, immature woven bone and highly differentiated hyaline cartilage. The fibro-osseous components exhibited positive immunoreaction with SATB2 and a low Ki-67 proliferation index. The fibro-osseous and cartilaginous components shared mutations at codon 201 in exon 8 of the guanine nucleotide-binding protein/a-subunit (GNAS)gene, specifically CGT>CAT (p.R201H) in four patients and the wild-type isocitrate dehydrogenase (IDH)1/IDH2gene. Telomerase reverse transcriptase (TERT)promoter mutations (C288T and C229G) occurred in both fibro-osseous and cartilaginous components in two patients.ConclusionsFCD encompasses areas of conventional FD with additional cartilage. Importantly, the presence or absence of mutations in theGNASgene and/or theTERTpromoter is common between the fibro-osseous and cartilaginous components of the disease. These results further confirmed FCD as a variant of FD.
Effect of Universal Credit on young children’s mental health: quasi-experimental evidence from Understanding Society
Authors: Song Huihui , Zhang Anwen , Barr Benjamin , Wickham Sophie 
Published: August 2024

BackgroundChild mental health has become an increasingly important issue in the UK, especially in the context of significant welfare reforms. Universal Credit (UC) has introduced substantial changes to the UK’s social security system, significantly impacting low-income families. Our aim was to assess the effects of UC’s introduction on children’s mental health for families eligible for UC versus a comparable non-eligible sample.MethodsUsing Understanding Society data from 5806 observations of 4582 children (aged 5 or 8 years) in Great Britain between 2012 and 2018, we created two groups: children whose parents were eligible for UC (intervention group) and children whose parents were ineligible for UC (comparison group). Child mental health was assessed using a parent-reported Strengths and Difficulties Questionnaire. The OR and percentage point change in the prevalence of children experiencing mental health difficulties between the intervention group and the comparison group following the introduction of UC were analysed. We also investigated whether the utilisation of childcare services and changes in household income were mechanisms by which UC impacted children’s mental health.ResultsLogistic regression results demonstrated that the prevalence of mental health problems among eligible children whose parents were unemployed increased by an OR of 2.18 (95% CI 1.14 to 4.18), equivalent to an 8-percentage point increase (95% CI 1 to 14 percentage points) following the introduction of UC, relative to the comparison group. Exploring potential mechanisms, we found neither reduced household income nor increased use of childcare services, which served as a proxy for reduced time spent with parents, significantly influenced children’s mental health.ConclusionsUC has led to an increase in mental health problems among recipient children, particularly for children in larger families and those aged 8. Policymakers should carefully evaluate the potential health consequences for specific demographics when introducing new welfare policies.
Circulating extracellular vesicles in Systemic Lupus Erythematosus: physicochemical properties and phenotype
Authors: Losada Paula X , Serrato Lina , Daza Ana María , Vanegas-García Adriana , Muñoz Carlos H , Rodriguez Daniel , Diaz Juan Camilo , Pineda Ricardo , Rojas Lopez Mauricio , Vásquez Gloria 
Published: August 2024

ObjectiveThis study aimed to identify the physicochemical and phenotypic characteristics of circulating Extracellular Vesicles (EVs) in the plasma of patients with SLE, with or without Lupus Nephritis (LN), and their potential utility as disease biomarkers.MethodsPlasma-circulating EVs were concentrated using differential centrifugation from adult female patients (n=38) who met the ‘American College of Rheumatology/European Alliance of Associations for Rheumatology 2019’ criteria for SLE diagnosis with (LN) or without LN (nLN), confirmed by renal biopsy. Controls (n=18) were healthy volunteers matched by gender and similar age. The structure, size and Energy Dispersion Spectrum (EDS) of EVs were observed by electron microscopy. The surface charge and size distribution were evaluated using dynamic light scattering. The counts and phenotype of EVs from patients (SLE-EVs) and controls (Ctrl-EVs) were obtained using flow cytometry. Non-parametric statistical tests and exploratory analysis of multiple variables were performed. The discriminatory power of some variables as potential biomarkers of the disease was also evaluated.ResultsCirculating EVs were heterogeneous in morphology and size, but SLE-EVs reached larger diameters than Ctrl-EVs (p<0.0001). Small SLE-EVs and large SLE-EVs were increased compared with Ctrl-EV (p<0.0001 and p<0.05, respectively). Likewise, patients with SLE (LN or nLN) had higher concentrations of large EVs compared with controls (p<0.001 and p<0.0001, respectively). SLE-EVs showed a different EDS (p<0.001) and were less electronegative (p<0.0001) than Ctrl-EVs. EV-CD45+, EV-CD14+ and EV-IgM+ were more frequent in patients with SLE compared with controls (p<0.001, p<0.05 and p<0.001, respectively). The concentrations of large EVs and EV-IgM+ allowed better discrimination of patients from controls.ConclusionsPlasma-circulating EVs from patients with SLE with and without nephritis are increased in peripheral blood and have different physicochemical properties than controls. Characteristics of EVs such as larger size and the presence of IgM on the surface could help discriminate patients from controls.
Criteria for continuous neuraxial analgesia associated with reduced mortality in patients undergoing thoracotomy
Authors: Semmelmann Axel , Baar Wolfgang , Moneke Isabelle , Loop Torsten 
Published: August 2024

IntroductionBoth thoracic epidural analgesia and thoracic paravertebral analgesia are effective techniques to control pain and minimize the stress response following thoracic surgery. We hypothesized that continuous neuraxial techniques may be associated with a decrease in the incidence of postoperative mortality after thoracotomy. Additionally, we aimed to identify subgroup populations that may benefit more from neuraxial anesthesia.Method1620 patients who underwent open thoracotomy were included in this retrospective study from the German Thoracic Registry database at four university hospitals. All-cause inpatient mortality was determined for patients who had and did not have neuraxial anesthesia. Logistic regression was used to adjust for and explore various covariates.ResultsContinuous neuraxial analgesia was associated with a lower overall mortality in the postoperative period (2.9%, 23/796 vs 5.3%, 44/824, p=0.02) only after the univariate analysis but not the multivariable analysis (OR 0.49, 95 % CI 0.237 to 1.12, p=0.15). In patients with epidural or paravertebral catheters, mortality was significantly lower in the following subgroups: age >75 (5/113 vs 18/77, OR 0.1, 95% CI 0.02 to 0.67, p=0.02), American Society of Anesthesiologists Performance Score >III (11//97 vs 33/155, OR 0.32, 95% CI 0.11 to 0.89, p=0.03), chronic kidney disease (5/83 vs 16/77, OR 0.16, 95% CI 0.03 to 0.82, p=0.03), and postoperative sepsis (9/21 vs 17/25, OR 0.13, 95% CI 0.07 to 0.44, p<0.01).ConclusionsNeuraxial analgesic techniques are associated with reductions in postoperative mortality after open thoracic surgery in selected patients.