bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of hypercapnia and mortality in home mechanical ventilation: the population-based DISCOVERY study
Authors: Palm Andreas , Ekström Magnus , Emilsson Össur , Ersson Karin , Ljunggren Mirjam , Sundh Josefin , Grote Ludger 
Published: August 2024

BackgroundStudies on the survival of patients with home mechanical ventilation (HMV) are sparse. We aimed to analyse the impact of controlled hypercapnia on survival over 27 years among patients with HMV in Sweden.Study design and methodsPopulation-based cohort study of adult patients starting HMV in the Swedish Registry for Respiratory Failure (Swedevox) during 1996–2022 cross-linked with the National Cause of Death registry. Mortality risk factors were analysed using crude and multivariable Cox regression models, including adjustments for anthropometrics, comorbidities, the underlying diagnosis causing chronic hypercapnic respiratory failure (CRF) and the control of hypercapnia (PaCO2≤6.0 kPa) at follow-up.ResultsWe included 10 190 patients (50.1% women, age 62.9±14.5 years). Control of hypercapnia at follow-up after 1.3±0.9 years was associated with lower mortality, hazard ratio (HR) 0.74 (95% CI 0.68–0.80) and the association was strongest in those with pulmonary disease, restrictive thoracal disease (RTD), obesity hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS). Predictors for increased mortality included age, Charlson Comorbidity Index, supplemental oxygen therapy and acute start of HMV therapy. Median survival varied between 0.8 years (95% CI 0.8–0.9 (n=1401)) for ALS and 7.6 years (95% CI 6.9–8.6 (n=1061)) for neuromuscular disease. Three-year survival decreased from 76% (95% CI 71–80) between 1996 and 1998 to 52% (95% CI 50–55) between 2017 and 2019. When adjusting for underlying diagnosis and age, the association between start year and decreased survival disappeared, HR 1.00 (95% CI 0.99–1.01).ConclusionControllingPaCO2is a key treatment goal for survival in HMV therapy. Survival differed markedly between diagnosis and age groups, and survival rates have declined as the patient group has aged.
Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial
Authors: Chalmers James D. , Loebinger Michael R. , Teper Ariel , McShane Pamela J. , Fernandez Carlos , Fucile Sebastian , Haworth Charles S. , Lauterio Melanie , van der Laan Roald , Shih Vivian H. , Metersky Mark L. 
Published: August 2024

IntroductionBronchiectasis is a chronic inflammatory airway disease. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces pulmonary inflammation by preventing the activation of neutrophil serine proteases. In the phase II WILLOW trial, brensocatib prolonged time to first exacerbation in patients with bronchiectasis. In thispost hocanalysis we compare clinical outcomes in patients from WILLOW according to baseline disease characteristics.MethodsAdults with bronchiectasis treated with brensocatib (10 or 25 mg) or placebo once daily were analysed by baseline Bronchiectasis Severity Index (BSI) score (≤4 (mild), 5–8 (moderate), or ≥9 (severe)), exacerbation history (2 or ≥3 in the previous year), blood eosinophil count (<300 cells per µL or ≥300 cells per µL), long-term macrolide use (≥6 months; no or yes) andPseudomonas aeruginosaculture at screening (negative or positive). End-points were time to first exacerbation, annualised exacerbation rate, change in lung function from baseline, and safety. All patients who received brensocatib were pooled and compared with placebo.ResultsTreatment with brensocatibversusplacebo was associated with a longer time to first exacerbation (hazard ratio (95% confidence interval), BSI: ≤4, 0.28 (0.08–0.96); 5–8, 0.75 (0.35–1.60); ≥9, 0.61 (0.35–1.04); prior exacerbations: 2, 0.56 (0.34–0.90); ≥3, 0.71 (0.32–1.59); blood eosinophils per µL: <300, 0.66 (0.42–1.06); ≥300, 0.49 (0.20–1.20); long-term macrolide use: no, 0.60 (0.38–0.94); yes, 0.60 (0.25–1.45);P. aeruginosaculture: negative, 0.54 (0.32–0.92); positive, 0.68 (0.37–1.27)). Safety results were similar across subgroups.DiscussionPatients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbationversusplacebo across all key baseline disease characteristics.
Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis
Authors: Araújo Márcia , Beltrão Marília , Sokhatska Oksana , Melo Natália , Caetano Mota Patrícia , Bastos Helder Novais , Terras André , Coelho David , Delgado Luís , Morais António 
Published: August 2024

IntroductionProgressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs. This study aimed to investigate the role of serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.MethodsNewly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline and disease progression was monitored. PPF was defined according to the recent European Respiratory Society, American Thoracic Society, Japanese Respiratory Society and the Latin American Thoracic Society Clinical Practice Guidelines.Results79 patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (adjusted OR 1.263, 95% CI 1.029–1.551; p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL−1for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.ConclusionsIn patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.
Effectiveness of early Anakinra on cardiac function in children with multisystem inflammatory syndrome of COVID-19: a systematic review
Authors: Shabil Muhammed , Khatib Mahalaqua Nazli , Banda Godfrey T , Zahiruddin Quazi Syed , Ballal Suhas , Bansal Pooja , Srivastava Manish , Arora Isha , Kumar M Ravi , Sinha Aashna , Pant Kumud , Al-Jishi Jumana M. , Albayat Hawra , Al Fares Mona A. , Garout Mohammed , Alrasheed Hayam A , Al-Subaie Maha F. , Rabaan Ali A. 
Published: August 2024

Abstract
Background
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C.

Methods
A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale.

Results
Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra’s role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements.

Conclusion
Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra’s effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols.
Facilitators and barriers to implementing successful exclusion among children with shiga toxin-producing Escherichia coli: a qualitative analysis of public health case management records
Authors: Vusirikala Amoolya , Yanshi  , Robin Charlotte , Rowell Sam , Dabke Girija , Fox Georgina , Bell Jade , Manuel Rohini , Jenkins Claire , Love Nicola K , McCarthy Noel , Sumilo Dana , Balasegaram Sooria 
Published: August 2024

Abstract
Background
Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health concern as they can cause serious illness and outbreaks. In England, STEC incidence is highest among children and guidance recommends that children under six diagnosed with STEC are excluded from childcare until two consecutive stool cultures are negative. We aimed to describe the barriers and facilitators to implementing exclusion and the impact of exclusion policies on young children and their families.

Methods
Individual level data was obtained from a wider study focusing on shedding duration among STEC cases aged < 6 years between March 2018 – March 2022. Data was extracted from England’s public health case management system. The case management system includes notes on telephone conversations, email correspondence and meeting minutes relating to the case. Collected data consisted of free text in three forms: (1) quotes from parents, either direct or indirect, (2) direct quotes from the case record by health protection practitioners or environmental health officers, and (3) summaries by the data collector after reviewing the entire case record. We analysed free text comments linked to 136 cases using thematic analysis with a framework approach.

Results
The median age of included cases was 3 years (IQR 1.5-5), with males accounting for 49%. Nine key themes were identified. Five themes focused on barriers to managing exclusion, including (i) financial losses, (ii) challenges with communication, engagement and collaboration, (iii) issues with sampling, processing, and results, (iv) adverse impact on children and their families and (v) conflicting exclusion advice. Four themes related to facilitators to exclusion, including (i) good communication with parents and childcare settings, (ii) support with childcare, (iii) improvements to sampling, testing, and reporting of results, and (iv) provision of supervised control measures.

Conclusions
Qualitative analysis of public health case records can provide evidence-based insights around complex health protection issues to inform public health guidelines. Our analysis highlights the importance of considering wider social and economic consequences of exclusion when developing policies and practices for the management of STEC in children.
Oral health knowledge, attitudes, and practices of people living with mental illness: a mixed-methods systematic review
Authors: Johnson Alisha Maree , Kenny Amanda , Ramjan Lucie , Raeburn Toby , George Ajesh 
Published: August 2024

AbstractPeople living with mental illness experience poorer oral health outcomes compared to the general population, yet little is known about their oral health knowledge, attitudes, and practices. The aim of this mixed-methods systematic review was to synthesise evidence regarding oral health knowledge, attitudes, and practices of people living with mental illness to inform preventative strategies and interventions. Database searches were conducted in PubMed, MEDLINE, PsycINFO, CINAHL, ProQuest, and Scopus with no limitations placed on the year of study. All studies available in the English language, that explored the oral health knowledge, attitudes, and/or practices of people with a mental illness were included. Articles were excluded if they primarily pertained to intellectual disability, behavioural and psychological symptoms of dementia, drug and alcohol or substance use, or eating disorders. A thematic synthesis was undertaken of 36 studies (26 high-moderate quality), resulting in 3 themes and 9 sub-themes. Study participants ranged from n = 7 to n = 1095 and aged between 15–83 years with most having a diagnosis of schizophrenia, schizoaffective, or bipolar affective disorder. People diagnosed with a mental illness were found to have limited oral health knowledge, particularly regarding the effects of psychotropic medication. Various barriers to oral health care were identified, including high dental costs, the negative impact of mental illness, dental fears, lack of priority, and poor communication with dental and health care providers. Study participants often displayed a reduced frequency of tooth brushing and dental visits. The findings highlight the potential for mental health care providers, oral health and dental professionals, mental health consumers, and carers to work together more closely to improve oral health outcomes for people with mental illness. The systematic review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO), (registration ID CRD42022352122).
Pediatric head injury guideline use in Sweden: a cross-sectional survey on determinants for successful implementation of a clinical practice guideline
Authors: Wickbom Fredrik , Berghog William , Bernhardsson Susanne , Persson Linda , Kunkel Stefan , Undén Johan 
Published: August 2024

Abstract
Background
The Scandinavian Neurotrauma Committee guideline (SNC-16) was developed and published in 2016, to aid clinicians in management of pediatric head injuries in Scandinavian emergency departments (ED). The objective of this study was to explore determinants for use of the SNC-16 guideline by Swedish ED physicians.

Methods
This is a nationwide, cross-sectional, web-based survey in Sweden. Using modified snowball sampling, physicians managing children in the ED were invited via e-mail to complete the validated Clinician Guideline Determinants Questionnaire between February and May, 2023. Baseline data, data on enablers and barriers for use of the SNC-16 guideline, and preferred routes for implementation and access of guidelines in general were collected and analyzed descriptively and exploratory with Chi-square and Fisher's tests.

Results
Of 595 invitations, 198 emergency physicians completed the survey (effective response rate 33.3%). There was a high reported use of the SNC-16 guideline (149/195; 76.4%) and a strong belief in its benefits for the patients (188/197; 95.4% agreement). Respondents generally agreed with the guideline's content (187/197; 94.9%) and found it easy to use and navigate (188/197; 95.4%). Some respondents (53/197; 26.9%) perceived a lack of organizational support needed to use the guideline. Implementation tools may be improved as only 58.9% (116/197) agreed that the guideline includes such. Only 37.6% (74/197) of the respondents agreed that the guideline clearly describes the underlying evidence supporting the recommendation. Most respondents prefer to consult colleagues (178/198; 89.9%) and guidelines (149/198; 75.3%) to gain knowledge to guide clinical decision making. Four types of enablers for guideline use emerged from free-text answers: ease of use and implementation, alignment with local guidelines and practice, advantages for stakeholders, and practicality and accessibility. Barriers for guideline use were manifested as: organizational challenges, medical concerns, and practical concerns.

Conclusions
The findings suggest high self-reported use of the SNC-16 guideline among Swedish ED physicians. In updated versions of the guideline, focus on improving implementation tools and descriptions of the underlying evidence may further facilitate adoption and adherence. Measures to improve organizational support for guideline use and involvement of patient representatives should also be considered.
Plexin C1 influences immune response to intracellular LPS and survival in murine sepsis
Authors: Bernard Alice , Eggstein Claudia , Tang Linyan , Keller Marius , Körner Andreas , Mirakaj Valbona , Rosenberger Peter 
Published: August 2024

Abstract
Background
Intracellular sensing of lipopolysaccharide (LPS) is essential for the immune response against gram-negative bacteria and results in activation of caspase-11 and pyroptotic cell death with fatal consequences in sepsis. We found the neuronal guidance receptor plexin C1 (PLXNC1) influences the intracellular response to LPS.

Methods
We employed a murine model of sepsis via cecal ligation and binding (CLP), using PLXNC1-/- mice and littermate controls, and additionally transfected murine bone-marrow-derived macrophages (BMDMs) from both genotypes with LPS to achieve activation of the noncanonical inflammasome ex vivo. Additionally, we transfected the PLXNC1 ligand SL4c-d in vivo and ex vivo to examine its effect on intracellular LPS response.

Results
We found the neuronal guidance receptor PLXNC1 dampens the intracellular response to LPS by interacting with adenylate cyclase 4 (ADCY4) and protein kinase A activity, which in turn diminishes caspase-11 expression. The absence of PLXNC1 results in excessive inflammation marked by increased cytokine release, increased secondary organ injury and reduced sepsis survival in a murine sepsis model induced by CLP. Notably, administration of SL4c-d—peptide ligand of PLXNC1—reduces the inflammatory response during CLP-induced sepsis and improves survival.

Conclusions
These results elucidate a previously unknown mechanism for PLXNC1 suppressing excessive noncanonical inflammasome activity and offer a new potential target for treatment of sepsis with its detrimental effects.
ECG changes following balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension: a retrospective study
Authors: Guo Tao , Zeng Xiao-mei , Huang Hou-quan , Wu Xiao-feng , Guo Wen-liang , Chen Hai-ming , Zhong Qiao-nan , Yang Xin , Ye Hui-ling , Hong Cheng 
Published: August 2024

Abstract
Purpose
This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods
Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results.

Results
BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range − 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score.

Conclusions
BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.
Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy
Authors: Chan Wei Yen , Lee Jenny H. , Stewart Ashleigh , Diefenbach Russell J. , Gonzalez Maria , Menzies Alexander M. , Blank Christian , Scolyer Richard A. , Long Georgina V. , Rizos Helen 
Published: August 2024

Abstract
Background
Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

Methods
Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.

Results
Pre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.

Conclusion
Post-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.