bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of an online intervention for parents/guardians of children aged 4–7 years who are concerned about their child’s emotional and behavioural development: protocol for an online randomised controlled trial (EMERGENT study)
Authors: Frings Daniel , Reavey Paula , Chew Jowinn , Leahy Michael , Allabyrne Clare , Herteliu Claudiu 
Published: June 2024

IntroductionThe demand for resources to support emotional and behavioural development in early childhood is ever increasing. However, conventional interventions are lacking in resources and have significant barriers. The Embers the Dragon programme helps address the growing unmet need of children requiring support. The delivery of the current project seeks to help support parents, reduce the burden placed on pressed services (eg, Child and Adolescent Mental Health Services) and to help improve the emotional and behavioural development of children.Methods and analysisThis project aims to investigate the efficacy and acceptability of Embers on parenting and children’s psychosocial outcomes. 364 parents/guardians of children aged between 4 and 7 will be recruited via the internet, schools and general practitioners (GPs). This is an online waitlist-controlled trial with three arms: (1) control arm, (2) access to Embers arm and (3) access to Embers+school. Participants will be randomised (1:1) into (1) or (2) to evaluate the use of Embers at home. To evaluate scalability in schools, (3) will be compared with (2), and (1) to test efficacy against treatment as usual (not receiving the intervention). Qualitative interviews will also be conducted. Primary outcomes are the Parental Self-efficacy Scale, Strengths and Difficulties Questionnaire and qualitative interviews. Outcomes will be compared between the three groups at baseline, 8, 16 and 24 weeks.Ethics and disseminationEthical approval has been granted by the London South Bank University ethics panel (ETH2324-0004). To recruit via GPs, NHS ethical approval has been applied for, and the IRAS (331410) application is under consideration by the Central Bristol REC. The results of the project will be submitted for publication in a peer-reviewed journal. Parents/guardians will provide informed consent online prior to taking part in the study. For the interviews, assent will be taken from children by the researchers on the day.Trial registration numberISRCTN58327872
Potential health and economic impact of achieving Kenya’s overweight and obesity reduction target: a modelling study
Authors: Wanjau Mary Njeri , Aminde Leopold Ndemnge , Veerman J Lennert 
Published: June 2024

Introduction
Kenya has adopted the WHO target of halting the rise of overweight, including obesity, by 2025. This paper assesses the potential impact of achieving the set target on health, healthcare cost and productivity.

Methods

We used a proportional multistate life table model (
Kenya Obesity Model
) to simulate the 2019 population of Kenya over their lifetime. We compared a scenario in which body mass index (BMI) distributions stabilise in 2025 against one whose BMI distributions stabilise in 2044, and quantified changes in disease-specific health outcomes, healthcare costs and productivity. We searched the literature to identify the best estimates of the total and disease-specific healthcare costs in Kenya. We used the Human Capital Approach to estimate productivity gains.

Results
If BMI distributions stabilised in 2025, an estimated 6.8 million health-adjusted life years (HALYs) (95% uncertainty interval (UI) 5.8–7.9 million) would be saved over the lifetime of the 2019 Kenyan population (135 HALYs per 1000 persons). A total of US$755 million in body mass-related healthcare costs could be saved by 2044 (US$15 per capita). For context, this equates to 16% of Kenya’s annual healthcare expenditure. Over the lifetime, ~US$3 billion healthcare costs could be saved (US$62 per capita). By 2044, the total productivity gain resulting from a reduction in high BMI-related mortality and morbidity (combined) was ~US$5.8 billion (~US$237 per capita).

Conclusion
Achieving Kenya’s overweight and obesity reduction target could improve health outcomes and also yield substantial healthcare cost savings and productivity gains.
Exploring the attitudes of solid organ transplant recipients towards COVID-19 shielding communications and the language of ‘clinically extremely vulnerable’: a qualitative study investigating lessons for the future
Authors: Greig Abbie E , Rennie Kirsten L , Ali Jason , Summers Dominic 
Published: June 2024

Introduction
Solid organ transplant (SOT) recipients were among the first individuals in the UK identified as ‘clinically extremely vulnerable’ (CEV) to COVID-19 and asked to ‘shield’ at the beginning of the pandemic in March 2020. This qualitative study explores the attitudes of SOT recipients towards COVID-19 shielding communications and the language used.

Methods
Semistructured interviews were conducted with 43 adult heart, liver and kidney transplant recipients in England between January 2022 and May 2023. Open-ended questions enabled participants to fully explore their experiences of the pandemic and how they felt towards the shielding advice they received. Interviews were transcribed, anonymised and thematically analysed and coded using NVivo V.12.

Results
Communications about shielding evoked significant fear and anxiety among participants. These communications were perceived as implying that death was probable, or even inevitable, should they leave their home or fail to follow the official advice. Participants expressed widespread dislike for the term ‘CEV’, with the word ‘vulnerable’ being particularly difficult for participants to accept owing to its connotations of weakness and the reminder that participants were not as ‘normal’ as they typically felt. While shielding restrictions have come to an end, longer term impacts were highlighted by participants who expressed ongoing anxiety, with many still choosing to shield and wear a mask if in public.

Conclusions
This study suggests that governments and health authorities should carefully consider how they communicate with individuals with underlying health conditions in future public health emergencies. We have developed recommendations for how to improve shielding communications in the future, including replacing the phrase ‘CEV’ with that of ‘higher risk’, avoiding using those at higher risk as a national benchmark for risk of illness and death and providing more balanced and engaged communication and advice that takes into consideration the importance of mental well-being.
Inhaled corticosteroids andStenotrophomonas maltophiliain outpatients with chronic obstructive pulmonary disease: a retrospective cohort study
Authors: Rønn Christian , Kamstrup Peter , Heerfordt Christian Kjer , Sivapalan Pradeesh , Eklöf Josefin , Boel Jonas Bredtoft , Ostergaard Christian , Dessau Ram Benny , Moberg Mia , Janner Julie , Ulrik Charlotte Suppli , Jensen Jens-Ulrik Stæhr 
Published: June 2024

ObjectivesInhaled corticosteroids (ICS) are widely used in patients with chronic obstructive pulmonary disease (COPD). However, ICS are associated with an increased risk of adverse effects.We aimed to determine whether an association between a lower respiratory tract culture withStenotrophomonas maltophiliaand increasing ICS dosing in patients with COPD exists.DesignAn observational cohort study of outpatients with COPD in Denmark between 2010 and 2018.ICS exposure was categorised into four groups based on average daily consumption 1 year prior to inclusion: no use, low ICS dose (≤400 µg), moderate ICS dose (400–800 µg) and high ICS dose (>800 µg). Dose–response relationship was investigated by a multivariable Cox proportional hazards regression.ResultsOf the total 22 689 patients, 459 had lower respiratory tract cultures positive forS. maltophilia. The HR ofS. maltophiliaincreased with increasing daily ICS dose: low ICS dose HR 2.6 (95% CI 1.6 to 4.0), moderate ICS dose HR 3.0 (95% CI 1.9 to 4.6) and high ICS dose HR 5.7 (95% CI 3.8 to 8.5).ConclusionsWe found that ICS was associated with a high, dose-dependent increased hazard ofS. maltophiliain outpatients with COPD. High dose users had a nearly six times increased hazard compared with non-users of ICS. When appropriate, attempts at de-escalating ICS treatment should be made.
Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK)
Authors: Fisher Andrew J , White Michael , Goudie Nicola , Kershaw Anneka , Phillipson Julia , Bardgett Michelle , Lally Joanne , Bevin-Nicholls Alex , Chadwick Thomas , Bryant Andrew , Russell Sian , Smith Hesther , Frisby Laura , Errington Rebecca , Carby Martin , Thompson Richard , Santhanakrishnan Karthik , Parmar Jasvir , Lordan James L , Vale Luke , Hancock Helen , Exley Catherine , Gennery Andrew R , Wason James MS 
Published: June 2024

BackgroundLong-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone.Methods and analysisE-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials.Ethics and disseminationThe East Midlands—Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings.Trial registration numberEudraCT number 2022-002659-20;NCT10615985.
Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial
Authors: Pope Ian , Clark Lucy V , Clark Allan , Ward Emma , Belderson Pippa , Stirling Susan , Parrott Steve , Li Jinshuo , Coats Tim , Bauld Linda , Holland Richard , Gentry Sarah , Agrawal Sanjay , Bloom Benjamin Michael , Boyle Adrian A , Gray Alasdair J , Morris M Geraint , Livingstone-Banks Jonathan , Notley Caitlin 
Published: June 2024

Background
Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking.

Methods
In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months.

Results
An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported.

Conclusions
An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events.

Trial registration number

NCT04854616
.
Molecular assessment of intratumoral immune cell subsets and potential mechanisms of resistance to odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Brouwer-Visser Jurriaan , Fiaschi Nathalie , Deering Raquel P , Cygan Kamil J , Scott Darius , Jeong Se , Boucher Lauren , Gupta Namita T , Gupta Suraj , Adler Christina , Topp Max S , Bannerji Rajat , Duell Johannes , Advani Ranjana H , Flink Dina M , Chaudhry Aafia , Thurston Gavin , Ambati Srikanth R , Jankovic Vladimir 
Published: June 2024

BackgroundPatients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1;NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab.MethodsPatients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing.ResultsBaseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here.ConclusionsThis biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.
Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases
Authors: Goto Kensuke , Koyanagi Yoshito , Akiyama Masato , Murakami Yusuke , Fukushima Masatoshi , Fujiwara Kohta , Iijima Hanae , Yamaguchi Mitsuyo , Endo Mikiko , Hashimoto Kazuki , Ishizu Masataka , Hirakata Toshiaki , Mizobuchi Kei , Takayama Masakazu , Ota Junya , Sajiki Ai Fujita , Kominami Taro , Ushida Hiroaki , Fujita Kosuke , Kaneko Hiroki , Ueno Shinji , Hayashi Takaaki , Terao Chikashi , Hotta Yoshihiro , Murakami Akira , Kuniyoshi Kazuki , Kusaka Shunji , Wada Yuko , Abe Toshiaki , Nakazawa Toru , Ikeda Yasuhiro , Momozawa Yukihide , Sonoda Koh-Hei , Nishiguchi Koji M 
Published: June 2024

Background
As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP–allied diseases.

Methods
We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.

Results

A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with
EYS
accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.

Conclusion
A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.
Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1
Authors: olde Heuvel Florian , Li Zhenghui , Riedel Daniel , Halbgebauer Steffen , Oeckl Patrick , Mayer Benjamin , Gotzman Nina , Shultz Sandy , Semple Bridgette , Tumani Hayrettin , Ludolph Albert C , Boeckers Tobias Maria , Morganti-Kossmann Cristina , Otto Markus , Roselli Francesco 
Published: June 2024

BackgroundBiomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored.MethodsSingle-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls.ResultsCSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome.ConclusionSynaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.
Blood pressure status, trajectories and cardiovascular disease: the CoLaus|PsyCoLaus prospective study
Authors: Chocron Yaniv , Rousakis Markos , Vollenweider Peter , Vaucher Julien , Marques-Vidal Pedro-Manuel 
Published: June 2024

BackgroundHigh blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Adequate treatment of high BP should reduce the risk of CVD, but this association has seldom been assessed in a general population setting.MethodsPopulation-based prospective study conducted in Lausanne, Switzerland, with a follow-up between 2003 and 2021. Participants were categorised as normal BP, untreated high BP, treated and uncontrolled BP and treated and controlled BP. Total and CVD mortality as well as any CVD event were assessed.Results5341 participants (65% normal, 17.4% untreated, 8.8% treated and uncontrolled and 8.8% treated and controlled) were included. After a median follow-up of 14 years (IQR: 11–15), 575 CVD events occurred. Relative to participants with normal BP, multivariable-adjusted HRs (and 95% CI) for total CVD were 1.38 (1.11 to 1.72) for untreated, 1.35 (1.04 to 1.76) for treated and uncontrolled and 1.50 (1.15 to 1.95) for treated and controlled. The corresponding HRs for CVD mortality (112 events) were 0.94 (0.52 to 1.70), 1.77 (1.00 to 3.12) and 2.52 (1.50 to 4.23), respectively. For total mortality (677 events), the HRs were 1.24 (1.01 to 1.52), 1.26 (0.99 to 1.60) and 1.27 (0.99 to 1.62), respectively. Sensitivity analysis using BP status during a 5-year period and categorising participants as always normal, always treated and uncontrolled, always treated and controlled and other led to similar findings.ConclusionOver a long follow-up period of 14 years, BP control was not associated with reduction of CVD events, CVD-related or total mortality. This finding should help define further studies on factors affecting CVD and mortality in people treated for hypertension in the general population.