bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping experiences of pathological demand avoidance in Ireland
Authors: Doyle Alison , Kenny Neil 
Published: November 2022

Pathological demand avoidance (PDA) is contended to be a distinct presentation within autism characterised by extreme levels of anxiety in response to the demands of everyday life, manifested in excessive levels of demand avoidance. This results in complex interactions with service providers in education and health settings, impacting on outcomes for individuals and their families. This national study sought to gather the viewpoints of individuals who experience PDA, families, and practitioners, with the intention of determining levels of knowledge, recognition and understanding of PDA; exploring current pathways to assessment and diagnosis; capturing experiences of access to education and healthcare services; identifying effective intervention and support strategies; and illuminating education and health outcomes for individuals and families. This mixed‐method study collates survey responses from N = 264 parents, N = 9 life partners, N = 6 individuals experiencing PDA and N = 54 practitioners, and in‐depth individual and focus group interviews from these cohorts. Findings suggest that a flexible, informed and individualised approach to assessment and service provision for individuals presenting with a PDA profile is essential. Practitioners universally referred to the necessity for a streamlined, integrated and multi‐disciplinary approach. The reported disconnect between education and health systems indicates a need for access to services on an equitable basis.
The European refugee crisis and public support for the externalisation of migration management
Authors: VRÂNCEANU ALINA , DINAS ELIAS , HEIDLAND TOBIAS , RUHS MARTIN 
Published: November 2022

AbstractWhat preferences do people have for cross‐country cooperation on irregular migration and refugee protection? Existing research improves our understanding of how voters react to large‐scale inflows of asylum seekers, like those experienced by European countries in 2015–2016, and the type of asylum seekers and policies preferred by European citizens. We know less, however, about people's views concerning a particular European Union (EU) response to the so‐called ‘refugee crisis’, namely the cooperation with Turkey in March 2016 to stem inflows of asylum seekers and other migrants. To study such views, we build on several strands of the international relations literature exploring key determinants of public preferences for international cooperation on cross‐national issues, namely (a) sociotropic concerns, (b) humanitarian considerations, and (c) perceptions of fairness and reciprocity. Our research design leverages conjoint experiments conducted simultaneously in Germany, Greece and Turkey. We find that the three factors indeed play a role in explaining preferences in the three countries. Moreover, while respondents are favourable to several core features of the current EU–Turkey migration deal (regarding the return of irregular migrants, financial aid to refugees, and border controls), we also find evidence of public support for increased cooperation on resettlement and EU support to Greece to deal with migration, which goes beyond the status quo. In certain aspects of cooperation, public preferences seem to respond to interactions between policy dimensions that capture reciprocity. These findings have important implications for research on public preferences for asylum and migration policies and public support for international cooperation more generally.
Snapshot of suspected acute coronary syndrome assessment processes in the emergency department: A national cross‐sectional survey
Authors: Brownlee Emily , Greenslade Jaimi H , Kelly Anne‐Maree , Meek Robert A , Parsonage William A , Cullen Louise 
Published: November 2022

AbstractObjectiveThe Snapshot of Suspected ACS Assessment (SSAASY) study aims to describe the assessment processes for patients with suspected acute coronary syndrome (ACS) in Australian EDs, and to compare these processes with the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand (NHFA/CSANZ) guidelines.MethodsBetween March and May 2021, a cross‐sectional survey of Australian EDs was undertaken to investigate the assessment strategies used within the ED. All public and private hospitals identified as having dedicated EDs were invited to participate. Respondents provided data on hospital, ED and cardiac service characteristics. They also provided data on the risk stratification process recommended within their department (risk scores, troponin testing, objective testing for coronary artery disease). Awareness of the NHFA/CSANZ guidelines was assessed.ResultsResponses were received from 109/162 departments (67%). Most sites (n = 100, 92%) reported using dedicated protocols developed by ED clinicians that included risk stratification scores. Highly sensitive troponin assays were used at 103 (94%) sites. Serial troponin testing was performed over 2 h for low‐risk patients in 53 (49%) sites and 2–3 h for intermediate and high‐risk patients in 74 (68%) sites. Further investigations included exercise stress tests (48%) and stress echocardiography (38%), with 45% of sites ordering outpatient investigations.ConclusionsThe SSAASY study reported the strategies used to assess suspected ACS. In line with current NHFA/CSANZ guidelines, highly sensitive troponin assays are widely utilised. However, serial sampling intervals were longer than guideline recommendations, suggesting a translational gap between guidelines and clinical practice.
Comparative analysis of fish environmental DNA reveals higher sensitivity achieved through targeted sequence‐based metabarcoding
Authors: McCarthy Avery , Rajabi Hoda , McClenaghan Beverly , Fahner Nicole A. , Porter Emily , Singer Gregory A. C. , Hajibabaei Mehrdad 
Published: November 2022

AbstractEnvironmental DNA (eDNA)‐based methods of species detection are enabling various applications in ecology and conservation including large‐scale biomonitoring efforts. qPCR is widely used as the standard approach for species‐specific detection, often targeting a fish species of interest from aquatic eDNA. However, DNA metabarcoding has the potential to displace qPCR in certain eDNA applications. In this study, we compare the sensitivity of the latest Illumina NovaSeq 6000 NGS platform to qPCR TaqMan assays by measuring limits of detection and by analysing eDNA from water samples collected from Churchill River and Lake Melville, NL, Canada. Species‐specific, targeted next generation sequencing (NGS) assays had significantly higher sensitivity than qPCR, with limits of detection 14‐ to 29‐fold lower. For example, when analysing eDNA, qPCR detected Gadus ogac (Greenland cod) in 21% of samples, but targeted NGS detected this species in 29% of samples. General NGS assays were as sensitive as qPCR, while simultaneously detecting 15 fish species from eDNA samples. With over 34,000 fish species on the planet, parallel and sensitive methods such as NGS will be required to support effective biomonitoring at both regional and global scales.
A wastewater‐based evaluation of the effectiveness of codeine control measures in Australia
Authors: Tscharke Benjamin J. , O'Brien Jake W. , Ahmed Fahad , Nguyen Lynn , Ghetia Maulik , Chan Gary , Thai Phong , Gerber Cobus , Bade Richard , Mueller Jochen , Thomas Kevin V. , White Jason , Hall Wayne 
Published: November 2022

AbstractBackground and aimFrom 1 February 2018, codeine was rescheduled from an over‐the‐counter (OTC) to a prescription‐only medicine in Australia. We used wastewater‐based epidemiology to measure changes in population codeine consumption before and after rescheduling.MethodsWe analysed 3703 wastewater samples from 48 wastewater treatment plants, taken between August 2016 and August 2019. Our samples represented 10.6 million people, 45% of the Australian population in state capitals and regional areas in each state or territory. Codeine concentrations were determined by liquid chromatography–tandem mass spectrometry and converted to per‐capita consumption estimates using the site daily wastewater volume, catchment populations and codeine excretion kinetics.ResultsAverage per‐capita consumption of codeine decreased by 37% nationally immediately after the rescheduling in February 2018 [95% confidence interval (CI) = 35.3–39.4%] and substantially in all states between 24 and 51% (95% CI = 22.4–27.0% and 41.8–59.4%). The decrease was sustained at the lower level to August 2019. Locations with least pharmacy access decreased by 51% (95% CI = 41.7–61.7%), a greater decrease than 37% observed for those with greater pharmacy access (95% CI = 35.1–39.4%). Regional areas decreased by a smaller margin to cities (32 versus 38%, 95% CI = 30.2–34.1% versus 34.9–40.4%, respectively) from a base per‐capita usage approximately 40% higher than cities.ConclusionWastewater analysis shows that codeine consumption in Australia decreased by approximately 37% following its rescheduling as a prescription‐only medicine in 2018. Wastewater‐based epidemiology can be used to evaluate changes in population pharmaceutical consumption in responses to changes in drug scheduling.
NKG2D‐mediated cytotoxicity improves after primary surgery for high‐grade serous ovarian cancer
Authors: Israelsson Pernilla , Björk Emma , Nagaev Ivan , Nagaeva Olga , Lundin Eva , Mincheva‐Nilsson Lucia , Ottander Ulrika 
Published: November 2022

AbstractProblemTumors compromise the patients’ immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome‐induced impairment of NKG2D cytotoxicity in HGSC.Method of studyPaired pre‐ and post‐operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D‐mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture‐derived exosomes, previously studied by us, were used for comparison.ResultsHGSC exosomes from patients’ sera downregulated NKG2D‐mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D‐mediated cytotoxic response of the HGSC patients’ own NK cells in postoperative compared to preoperative samples was noted.ConclusionsSurgical removal of the primary tumor has a beneficial effect, relieving the exosome‐mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.
Biomarkers associated with the development of comorbidities in patients with atopic dermatitis: A systematic review
Authors: Broderick Conor , Ziehfreund Stefanie , van Bart Karin , Arents Bernd , Eyerich Kilian , Weidinger Stephan , Rastrick Joseph , Zink Alexander , Flohr Carsten ,   BIOMAP Consortium
Published: November 2022

AbstractBiomarkers associated with the development of comorbidities in atopic dermatitis (AD) patients have been reported, but have not yet been systematically reviewed. Seven electronic databases were searched, from database inception to September 2021. English language randomized controlled trials, prospective and retrospective cohort, and case–control studies that investigated the association between a biomarker and the development of comorbidities in AD patients were included. Two authors independently screened the records for eligibility, one extracted all data, and critically appraised the quality of studies and risk of bias. Fifty six articles met the inclusion criteria, evaluating 146 candidate biomarkers. The most frequently reported biomarkers were filaggrin mutations and allergen specific‐IgE. Promising biomarkers include specific‐IgE and/or skin prick tests predicting the development of asthma, and genetic polymorphisms predicting the occurrence of eczema herpeticum. The identified studies and biomarkers were highly heterogeneous, and associated with predominately moderate‐to‐high risk of bias across multiple domains. Overall, findings were inconsistent. High‐quality studies assessing biomarkers associated with the development of comorbidities in people with AD are lacking. Harmonized datasets and independent validation studies are urgently needed.
Cost‐effectiveness comparison of delayed versus immediate coloanal anastomosis following ultralow anterior resection for rectal cancer
Authors: Shannon Nicholas Brian , Seow‐En Isaac , Tan Emile Kwong‐Wei 
Published: November 2022

AbstractBackgroundFollowing ultralow anterior resection for distal rectal cancers, a coloanal anastomosis is usually created along with a defunctioning ileostomy (DI). Recent evidence suggests that abdominoperineal pull‐through with delayed coloanal anastomosis (DCAA) is a viable alternative to immediate coloanal anastomosis (ICAA), minimizing the risk of anastomotic leakage and avoiding the need for stoma creation with the risk of stoma‐associated morbidity. However, DCAA requires a longer initial hospitalization. We aimed to perform a cost‐effectiveness analysis to compare DCAA versus ICAA for elective rectal cancer surgery.MethodsA decision tree model was used to compare the cost‐effectiveness of the two strategies. Cost data were obtained from the 2019 to 2020 United Kingdom National Health Service reference costs. Model probabilities were derived from published studies. Univariate and probabilistic sensitivity analyses were used to evaluate the robustness of the results.ResultsDCAA was the overall cheaper strategy at £13 541 compared with £14 856 for ICAA in the base case analysis. This was explained by the decreased overall costs of hospitalization/surgery, reduction in costs associated with anastomotic or stoma‐related complications, specifically dehydration‐induced hospital readmissions and avoidance of stoma maintenance costs. Sensitivity analysis demonstrated that DCAA remained consistently more inexpensive except when the duration of total parenteral nutrition exceeded 14 days.ConclusionDespite a longer index hospitalization with higher initial costs, this economic analysis demonstrates that DCAA without stoma is overall more cost‐effective compared with ICAA with DI following ultralow anterior resection. Cost savings should be considered an additional benefit when selecting the DCAA approach for rectal cancer surgery.
Foetal and neonatal exposure prediction and dosing evaluation for ampicillin using a physiologically‐based pharmacokinetic modelling approach
Authors: Li Sanwang , Xie Feifan 
Published: November 2022

AimsAmpicillin is frequently used in neonates for the treatment of sepsis and as an intrapartum prophylaxis option for Group B Streptococcus. Pharmacokinetic data to guide ampicillin dosing in neonates and during the intrapartum period are limited. The objective of this study was to build a physiologically‐based pharmacokinetic (PBPK) model to characterize the disposition of ampicillin in neonates and foetuses and to inform corresponding optimal dosing regimens.MethodsAn adult ampicillin PBPK model was first developed using the Simcyp® simulator. The adult model was then scaled to neonates by accounting for maturational changes in physiological parameters and age‐dependent drug disposition or extended to a pregnancy model for mothers and foetuses. Models were verified using collected mean or individual‐level concentration data from the literature.ResultsThe developed adult PBPK model included elimination via glomerular filtration, OAT3‐mediated tubular secretion and biliary excretion as well as hepatic metabolism, and 89.8% of the observed mean concentrations in adults were within a 2‐fold range of model mean predictions. Most of the observed individual‐level observations in neonates (78.4%) and foetuses (about 65% in two studies) were within the 90% prediction intervals. The recommended 50 mg/kg every 8 h (q8h) ampicillin regimen achieved the 75% fraction time of total drug concentration above minimum inhibitory concentration (T > MIC) target for an MIC ≤8 mg/L in >90% virtual neonates, and 1 g ampicillin for pregnant women provided adequate foetal exposure (>0.25 mg/L) for 4 h prior to delivery.ConclusionsA PBPK model was developed to characterize ampicillin's disposition in neonates, pregnant women, and foetuses, and the model supported optimal dosing evaluation in these vulnerable populations.
Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front‐line with paediatric‐inspired regimens: A retrospective multicentre Campus ALL study
Authors: Dargenio Michelina , Bonifacio Massimiliano , Chiaretti Sabina , Vitale Antonella , Fracchiolla Nicola Stefano , Papayannidis Cristina , Giglio Fabio , Salutari Prassede , Audisio Ernesta , Scappini Barbara , Zappasodi Patrizia , Defina Marzia , Forghieri Fabio , Scattolin Anna Maria , Todisco Elisabetta , Lunghi Monia , Guolo Fabio , Del Principe Maria Ilaria , Annunziata Mario , Lazzarotto Davide , Cedrone Michele , Pasciolla Crescenza , Imovilli Annalisa , Tanasi Ilaria , Trappolini Silvia , Cerrano Marco , La Starza Roberta , Krampera Mauro , Di Renzo Nicola , Candoni Anna , Pizzolo Giovanni , Ferrara Felicetto , Foà Robin 
Published: November 2022

SummaryWithin the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric‐inspired protocols between 2009 and 2020. Seventy‐one patients (6.8%) experienced a CNS recurrence, more frequently in T‐ (28/278; 10%) than in B‐ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse—< 12 months from diagnosis—was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T‐cell phenotype (p = <0.001), hyperleucocytosis >100 × 109/L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non‐transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2‐year post‐relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible.
Side‐chain cleavage enzyme deficiency: Systematic review and case series
Authors: Phadte Aditya , Arya Sneha , Sarathi Vijaya , Lila Anurag , Maheshwari Madhur , Memon Saba Samad , Rane Ankita , Patil Virendra , Rai Khushnandan , Raghav Darpan , Kunwar Ambarish , Bandgar Tushar 
Published: November 2022

AbstractObjectiveP450 side‐chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied.We describe our experience and perform a systematic review of genetically proven SCCD patients to determine the distinct phenotypic and genotypic characteristics of 46,XY SCCD patients with typical male external genitalia (SCCD‐TMG) and atypical (SCCD‐AG) external genitalia.Design, Patients and MeasurementsRetrospective review of three genetically proven SCCD patients from our centre and per‐patient data analysis from a systematic review of 52 probands was performed. SCCD‐TMG (n = 19) was defined as external genitalia of Sinnecker score 1 with 46,XY karyotype; the rest (Sinnecker 2–5) were classified as SCCD‐AG (n = 15).ResultsWe report two new Indian cases of SCCD with three novel likely pathogenic variants and pubertal follow‐up of a previously reported patient. In systematic review, age at diagnosis of PAI and elevated renin were not different between 46,XY SCCD‐TMG (n = 19) and SCCD‐AG (n = 15), whereas spontaneous puberty (9/9 vs. 0/3, p = .0045), normal prepubertal (5/5 vs. 6/6, p = .002), pubertal gonadotropins (2/9 vs. 0/3, p = 1) and normal pubertal testosterone (9/11 vs. 0/3, p = .027) were more common in SCCD‐TMG. Testicular adrenal rest tumours were exclusive to SCCD‐TMG (n = 4). SCCD‐TMG was associated with four particular genotypes [monoallelic p.Glu314Lys with another deleterious variant on the second allele (p.Glu314Lys/X‐CHS: X‐compound heterozygous state), biallelic p.Arg451Trp, p.Phe215Ser/p.Arg232Ter and monoallelic p.Val79Ile]. 46,XX SCCD patients with p.Glu314Lys/X‐CHS also had normal gonadotropins with spontaneous puberty.ConclusionSCCD‐TMG is associated with four specific genotypes and distinct gonadal characteristics from SCCD‐AG with overlapping features of PAI.
Safety of day‐case endoscopic sinus surgery in England: An observational study using an administrative dataset
Authors: Navaratnam Annakan V. , Pendolino Alfonso Luca , Andrews Peter J. , Saleh Hesham A. , Hopkins Claire , Randhawa Premjit S. , Little Sarah , Day Jamie , Briggs Tim W. R. , Gray William K. 
Published: November 2022

AbstractIntroductionAs elective surgical services recover from the COVID‐19 pandemic a movement towards day‐case surgery may reduce waiting lists. However, evidence is needed to show that day‐case surgery is safe for endoscopic sinus surgery (ESS). The aim of this study was to investigate the safety of day‐case ESS in England.DesignSecondary analysis of administrative data.MethodsWe extracted data from the Hospital Episodes Statistics database for the 5 years from 1 April 2014 to 31 March 2019. Patients undergoing elective ESS procedures aged ≥17 years were included. Exclusion criteria included malignant neoplasm, complex systemic disease and trans‐sphenoidal pituitary surgery. The primary outcome was readmission within 30 days post‐discharge. Multilevel, multivariable logistic regression modelling was used to compare outcomes for those operated on as day‐cases and those with an overnight stay after adjusting for demographic, frailty, comorbidity and procedural covariates.ResultsData were available for 49 223 patients operated on across 129 NHS hospital trusts. In trusts operating on more than 50 patients in the study period, rates of day‐case surgery varied from 20.6% to 100%. Nationally, rates of day‐case surgery increased from 64.0% in the financial year 2014/2015 to 78.7% in 2018/2019. Day‐case patients had lower rates of 30‐day emergency readmission (odds ratio 0.71, 95% confidence interval 0.62 to 0.81). Outcomes for patients operated on in trusts with ≥80% day‐case rates compared with patients operated on in trusts with <50% rates of day‐case surgery were similar.ConclusionsOur data support the view that ESS can safely be performed as day‐case surgery in most cases, although it will not be suitable for all patients. There appears to be scope to increase rates of day‐case ESS in some hospital trusts in England.