bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventions in Small Island Developing States to improve diet, with a focus on the consumption of local, nutritious foods: a systematic review
Authors: Haynes Emily , Augustus Eden , Brown Catherine R , Guell Cornelia , Iese Viliamu , Jia Lili , Morrissey Karyn , Unwin Nigel 
Published: October 2022

IntroductionFood security in Small Island Developing States (SIDS) is an international policy priority. SIDS have high rates of nutrition-related non-communicable diseases, including obesity and type 2 diabetes, micronutrient deficiencies and, in many, persistent childhood stunting. This is associated with an increasing reliance on imported processed food of poor nutritional quality. Calls have been made for strengthening local food systems, resilient to climate change, to increase the consumption of nutritious locally produced food. We aimed to systematically review interventions intended to improve diet in SIDS, and specifically explore whether these interventions applied a local food approach.MethodsThe search strategy was applied to 11 databases, including in health, social science and agriculture. Screening of titles, abstracts and data extraction was undertaken in duplicate. Risk of bias was assessed using Cochrane tools. Narrative synthesis of the results was undertaken. The study protocol was registered (PROSPERO registration number: 2020CRD42020201274).ResultsFrom 26 062 records, 154 full texts were reviewed and 24 were eligible. Included studies were from the Caribbean, Pacific, Mauritius and Singapore. Five were a randomised study design, one an interrupted time series analysis, eight controlled and ten uncontrolled pre-test and post-test. Nine studies included some aspect of a local food approach. Most interventions (n=15) included nutrition education, with evidence of effectiveness largely limited to those that also included practical skills training, such as vegetable gardening or food preparation. Three studies were considered low risk of bias, with the majority (n=13) of moderate risk.ConclusionThere is a lack of robust evidence on interventions to improve diet in SIDS. The evidence suggests that multifaceted approaches are likely to be the most effective, and local food approaches may promote effectiveness, through mechanisms of cultural and contextual relevance. Further development and evaluation of interventions is urgently required to increase the comparability of these studies, to help guide policy on improving nutrition in SIDS.
Cohort profile: the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS)
Authors: LeWinn Kaja Z , Karr Catherine J , Hazlehurst Marnie , Carroll Kecia , Loftus Christine , Nguyen Ruby , Barrett Emily , Swan Shanna H , Szpiro Adam A , Paquette Alison , Moore Paul , Spalt Elizabeth , Younglove Lisa , Sullivan Alexis , Colburn Trina , Byington Nora , Sims Taylor Lauren , Moe Stacey , Wang Sarah , Cordeiro Alana , Mattias Aria , Powell Jennifer , Johnson Tye , Norona-Zhou Amanda , Mason Alex , Bush Nicole R , Sathyanarayana Sheela 
Published: October 2022

PurposeExposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations.ParticipantsThe ECHO-PATHWAYS consortium harmonises extant data from 2684 mother–child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5–15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083).Findings to dateEarly analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution.Future plansThe first wave of data from the unified protocol (child age 8–9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.
Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation
Authors: Lowry Natalie , Cowden Fiona , Day Edward , Gilvarry Eilish , Johnstone Stacey , Murray Robbie , Kelleher Mike , Mitcheson Luke , Marsden John 
Published: October 2022

IntroductionOpioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).Methods and analysisThree qualitative–quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation.Ethics and disseminationStudy protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals.Trial registration number2018-004460-63.
Differentiating vaccine reactions from invasive bacterial infections in young infants presenting to the emergency department in the 4CMenB era: a retrospective observational comparison
Authors: Channon-Wells Samuel William , Tough Emily , So Neda , O'Connor Daniel , Snape Matthew D 
Published: October 2022

BackgroundDifferentiating infants with adverse events following immunisation (AEFIs) or invasive bacterial infection (IBI) is a significant clinical challenge. Young infants post vaccination are therefore often admitted to the hospital for parenteral antibiotics to avoid missing rare cases of IBI.MethodsDuring a service evaluation project, we conducted a single-centre retrospective observational study of infants with IBI, urinary tract infection (UTI) or AEFI from two previously published cohorts. All patients presented to hospital in Oxfordshire, UK, between 2011 and 2018, spanning the introduction of the capsular group-B meningococcal vaccine (4CMenB) into routine immunisation schedules. Data collection from paper and electronic notes were unblinded. Clinical features, including National Institute for Health and Care Excellence (NICE) ‘traffic light’ risk of severe illness and laboratory tests performed on presentation, were described, and comparisons made using regression models, adjusting for age and sex. We also compared biochemical results on presentation to those of well infants post vaccination, with and without 4CMenB regimens.ResultsThe study included 232 infants: 40 with IBI, 97 with probable AEFI, 24 with possible AEFI, 27 with UTI and 44 post vaccination ‘well’ infants. C-reactive protein (CRP) was the only discriminatory blood marker, with CRP values above 83 mg/L only observed in infants with IBI or UTI. NICE risk stratification was significantly different between groups but still missed cases of IBI, and classification as intermediate risk was non-differential. Fever was more common in probable AEFI cases, while seizures and rashes were equally frequent. Diarrhoea and clinician-reported irritability or rigours were all more common in IBI.ConclusionsClinical features on presentation may aid risk stratification but cannot reliably differentiate IBI from AEFI in infants presenting to the emergency department. Blood results are generally unhelpful due to post vaccination inflammatory responses, particularly in children receiving 4CMenB vaccination. Improved biomarkers and clinical prediction tools are required to aid management in febrile infants post vaccination.
Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO)
Authors: Wislez Marie , Mazieres Julien , Lavole Armelle , Zalcman Gérard , Carre Olivier , Egenod Thomas , Caliandro Raffaele , Dubos-Arvis Catherine , Jeannin Gaelle , Molinier Olivier , Massiani Marie-Ange , Langlais Alexandra , Morin Franck , Le Pimpec Barthes Francoise , Brouchet Laurent , Assouad Jalal , Milleron Bernard , Damotte Diane , Antoine Martine , Westeel Virginie 
Published: October 2022

BackgroundThe IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC).MethodsIn a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131).ResultsForty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8–41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3–5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity.ConclusionsNeoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.
Percutaneous left atrial appendage occlusion discrepancy between randomised trials and clinical practice
Authors: Kümler Thomas , Strange Jarl Emanuel , Andersen Niels Holmark 
Published: October 2022

In patients with atrial fibrillation and previous episodes of bleeding on oral anticoagulant treatment, left atrial appendage occlusion (LAAO) has emerged as an alternative way to decrease the risk of stroke.The use of the procedure has been on the rise, and the news coverage has been dominated by an uncritical acceptance of the benefit of this procedure, which probably have contributed to the increasing number of procedures.This commentary is a presentation and critical appraisal of the available evidence on the efficacy and safety of left atrial appendage closure as stroke prophylaxis.We illustrate that LAAO is supported by limited randomised data risk of serious complications, which we do not believe supports the current widespread use.
Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone
Authors: Imrich Richard , Sedláková Jana , Úlehlová Mária , Gornall Matthew , Jackson Richard , Olsson Birgitta , Rudebeck Mattias , Gallagher James , Lukáčová Oľga , Mlynáriková Vanda , Stančík Roman , Vrtíková Eva , Záňová Elizabeth , Zaťková Andrea , Arnoux Jean-Baptiste , Rovenský Jozef , Luangrath Emily , Bygott Helen , Khedr Milad , Ranganath Lakshminarayan R 
Published: October 2022

ObjectivesOchronotic spondyloarthropathy represents one of the main clinical manifestations of alkaptonuria (AKU); however, prospective data and description of the effect of nitisinone treatment are lacking.MethodsPatients with AKU aged 25 years or older were randomly assigned to receive either oral nitisinone 10 mg/day (N=69) or no treatment (N=69). Spine radiographs were recorded yearly at baseline, 12, 24, 36 and 48 months, and the images were scored for the presence of intervertebral space narrowing, soft tissue calcifications, vacuum phenomena, osteophytes/hyperostosis and spinal fusion in the cervical, thoracic and lumbosacral segment at each of the time points.ResultsAt baseline, narrowing of the intervertebral spaces, the presence of osteophytes/hyperostosis and calcifications were the three most frequent radiographic features in AKU. The rate of progression of the five main features during the 4 years, ranked from the highest to lowest was as follows: intervertebral spaces narrowing, calcifications, vacuum phenomena, osteophytes/hyperostosis and fusions. The rate of progression did not differ between the treated and untreated groups in any of the five radiographic parameters except for a slower rate of progression (sum of all five features) in the treatment group compared with the control group (0.45 (1.11) nitisinone vs 0.74 (1.11) controls, p=0.049) in the thoracic segment.ConclusionThe present study shows a relatively slow but significant worsening of radiographic features in patients with AKU over 4 years. Our results demonstrate a modest beneficial effect of 10 mg/day of nitisinone on the slowly progressing spondylosis in AKU during the relatively limited follow-up time.Trial registration numberNCT01916382.
Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking
Authors: Chatzidionysiou Katerina , di Giuseppe Daniela , Soderling Jonas , Catrina Anca , Askling Johan 
Published: October 2022

ObjectiveLung cancer is a common malignancy in rheumatoid arthritis (RA). Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself, increases lung cancer risk.MethodsWe performed a population-based cohort study of patients with RA and individually matched general population reference individuals identified in Swedish registers and from the Epidemiological Investigation of RA early RA study, prospectively followed for lung cancer occurrence 1995–2018. We calculated incidence rates and performed Cox regression to estimate HRs including 95% CIs of lung cancer, taking smoking and RA serostatus into account.ResultsOverall, we included 44 101 patients with RA (590 incident lung cancers, 56 per 100 000), and 216 495 matched general population individuals (1691 incident lung cancers, 33 per 100 000), corresponding to a crude HR (95% CI) of 1.76 (1.60 to 1.93). In subset analyses, this increased risk remained after adjustment for smoking (HR 1.77, 95% CI 1.06 to 2.97). Compared with general population subjects who were never smokers, patients with RA who were ever smokers had almost seven times higher risk of lung cancer. In RA, seropositivity was a significant lung cancer risk factor, even when adjusted for smoking, increasing the incidence 2–6 times. At 20 years, the risk in patients with RA was almost 3%, overall and over 4% for patients who were ever smokers and had at least one RA autoantibody.ConclusionsSeropositive RA is a risk factor for lung cancer over and above what can be explained by smoking, although residual confounding by smoking or other airway exposures cannot be formally excluded. There is a need for increased awareness and potentially for regular lung cancer screening, at least in a subset of patients with RA.
Sacroiliac joint radiographic progression in axial spondyloarthritis is retarded by the therapeutic use of TNF inhibitors: 12-year data from the SCQM registry
Authors: Micheroli Raphael , Kissling Seraphina , Bürki Kristina , Exer Pascale , Bräm René , Nissen Michael J , Möller Burkhard , Andor Michael , Distler Oliver , Scherer Almut , Ciurea Adrian 
Published: October 2022

ObjectivesTo analyse the effect of tumour necrosis factor inhibitors (TNFi) on sacroiliac joint (SIJ) radiographic progression in axial spondyloarthritis (axSpA).MethodsPatients with axSpA in the Swiss Clinical Quality Management cohort with up to 12 years of follow-up and radiographic assessments every 2 years were included. SIJs were scored by two readers according to the modified New York criteria blinded to chronology. The relationship between TNFi use before or during a 2-year radiographic interval and SIJ progression was investigated using generalised estimating equation models with adjustment for potential confounding. Progression was defined as worsening of ≥1 grade in ≥1 SIJ and ignoring a change from 0 to 1 over 2 years, if both readers agreed. A third reading of radiographs was integrated in sensitivity analyses.ResultsA total of 515 patients with axSpA contributed to data for 894 radiographic intervals (24 progression events). In patients with complete covariate data, prior use of TNFi reduced the odds of progression (OR 0.21, 95% CI 0.07 to 0.65). A comparable effect was found for use of TNFi for ≥1 year within a 2-year radiographic interval (OR 0.21, 95% CI 0.08 to 0.55). The inhibitory impact of TNFi was confirmed if progression was demonstrated in 2/3 readings: OR 0.50, 95% CI 0.28 to 0.89 and OR 0.46, 95% CI 0.27 to 0.78 for TNFi treatment before and for ≥1 year within the interval, respectively.ConclusionTNFi are associated with deceleration of SIJ radiographic progression in patients with axSpA if treatment is continued for ≥1 year.
Differential expansion of T peripheral helper cells in early rheumatoid arthritis and osteoarthritis synovium
Authors: Murray-Brown William , Guo Yanxia , Small Annabelle , Lowe Katie , Weedon Helen , Smith Malcolm D , Lester Susan E , Proudman Susanna M , Rao Navin L , Hao Ling-Yang , Nagpal Sunil , Wechalekar Mihir D 
Published: October 2022

ObjectivesProgrammed cell death protein 1 (PD-1)-expressing T cells are implicated in the pathogenesis of autoimmune inflammatory diseases such as rheumatoid arthritis. A subset of CXCR5−T cells, termed T peripheral helper (Tph) cells, which drive B cell differentiation, have been identified in ectopic lymphoid structures in established rheumatoid arthritis synovial tissue. Here, we aimed to characterise these in treatment-naïve, early rheumatoid arthritis to determine whether these cells accumulate prior to fully established disease.MethodsFresh dissociated tissue and peripheral blood mononuclear cell (PBMC) suspensions were stained with Zombie UV, followed by anti-CD45RO, PD-1, CD3, ICOS, CD8, CD4, CD20, CXCR5, TIGIT and CD38 antibodies prior to analysis. For histology, rheumatoid arthritis synovial sections were prepared for Opal multispectral immunofluorescence with anti-CD45RO, CD20, PD-1 and CXCR5 antibodies. Images were acquired on the Perkin Elmer Vectra V.3.0 imaging system and analysed using InForm Advanced Image Analysis software.ResultsFlow cytometry revealed T cell infiltration in the rheumatoid arthritis synovium with differential expression of PD-1, CD45RO, ICOS, TIGIT and CD38. We observed a higher frequency of PD1hiCXCR5−Tph in rheumatoid arthritis synovial tissue and PBMCs versus controls, and no significant difference in T follicular helper cell frequency. Microscopy identified a 10-fold increase of Tph cells in early rheumatoid arthritis synovial follicular and diffuse regions, and identified Tph adjacent to germinal centre B cells.ConclusionsThese data demonstrate that PD-1hiTph cells are present in early rheumatoid arthritis, but not osteoarthritis synovium, and therefore may provide a target for treatment of patients with early rheumatoid arthritis.