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AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physicians confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.

ABSTRACT Aim Design Findings Conclusion Implications for Profession and Patient Care Impact Reporting Method Patient and Public Contribution To discuss the multi‐centre qualitative methodology as a unique design, articulate its guiding paradigm/theoretical perspectives, and highlight its methodological and methodical issues. A secondary objective is to generate further scholarly discourse regarding the multi‐centre approach within the broader qualitative research tradition.Methodological discussion.Rather than an emphasis on only experiences, the multi‐centre approach is presented as a unique design which also focuses on uncovering why a phenomenon or problem exists and perceptions regarding the phenomenon/problem. With its focus on capturing multiple subjective realities, the multi‐centre qualitative design is arguably underpinned by pragmatist constructivism which offers a robust framework for researching phenomenon in a way that is both theoretically informed and practically relevant. Methodologically, the multi‐centre qualitative research design emphasises a problem‐centred enquiry, collaborative approach and rigorous study protocols, systematic site selection, contextual immersion and sensitivity and methodical flexibility.With the rapidly evolving nursing and global health landscape, the multi‐centre design lends itself to exploring and capturing perceptions on a larger scale compared to single site studies. Careful planning, availability of adequate resources, rigorous protocols and quality assurance plans are critical to ensuring its success.The multi‐centre approach offers the possibility of undertaking the same study across multiple settings/locations which has the potential to improve representation and strengthen transferability.This methodological discussion offers clarity regarding the use of the multi‐centre approach and offering strategies for its subsequent uptake in nursing and healthcare research.Not applicable.No patient or public contribution. [ABSTRACT FROM AUTHOR]

Aim Design Methods Results Conclusion Reporting Method Implication for the Profession Impact Patient or Public Contribution To explore the disruptive influence of workplace gaslighting behaviours and mobbing on nurses' career entrenchment across multiple healthcare centres.A multi‐centre cross‐sectional.Data were collected from 483 nurses from various healthcare settings in Egypt, spanning from January 2024 to February 2024. The Gaslighting at Work Questionnaire, Luxembourg Workplace Mobbing Scale and Career Entrenchment Scale were employed for data collection.The study revealed moderate levels of gaslighting, mobbing and nurses' career entrenchment. Also, there is a negative correlation between nurses' career entrenchment and both gaslighting and mobbing, while gaslighting and mobbing exhibit a positive correlation. The study also highlighted regional disparities in the prevalence of these phenomena, with the highest incidences noted in urban healthcare settings.The findings underscore the critical impact of workplace gaslighting and mobbing on nurses' career entrenchment.The relevant reporting method has been adhered to, that is, STROBE.The future of the nursing profession requires building productive nurses who can cope with negative workplace experiences. This could be achieved by cultivating a workplace culture that has zero tolerance for these experiences. Offering counselling services or employee assistance programmes to help nurses cope with the emotional toll of these negative experiences is a promising strategy.This study is the first to examine serious workplace practices like gaslighting and mobbing in a nursing context, emphasizing their effect on nursing‐sensitive indicators like career entrenchment. It is one of the important initiatives geared towards upgrading the competitiveness and magnetism of healthcare organizations in the era of green human resources management. Results provide valuable insights for nurse leaders to control nursing turnover and shortage crises in different endeavours.In our study, nurses from diverse geographical regions and varied specialties actively participate, offering a rich tapestry of experiences and perspectives. [ABSTRACT FROM AUTHOR]

Aims The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. Methods and results In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. Conclusion The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy. [ABSTRACT FROM AUTHOR]

Aims: To determine the contributions of different kinds of symptoms to the quality of life and mediating effect of psychological and physical symptoms between heart failure symptoms and quality of life. Design: A multi‐centre cross‐sectional study. Methods: 2006 chronic heart failure patients from four cities were recruited in China from January 2021 to December 2022. Patients' symptoms and quality of life were self‐reported, and data were analysed using correlation analysis, dominance analysis and mediating effects analysis. Results: The dominance analysis revealed that the overall mean contributions of heart failure, psychological and physical symptoms were.083,.085 and.111; 29.5%, 30.2% and 39.5% of the known variance. And heart failure symptoms could negatively affect quality of life through psychological and physical symptoms, accounting for 28.39% and 22.95% of the total effect. Heart failure symptoms could also affect quality of life through the chain‐mediated effect of physical and psychological symptoms, accounting for 16.74%. Conclusions: Physiological symptoms had the strongest effect on quality of life and heart failure symptoms had the weakest. Most of the effect for heart failure symptoms on quality of life in chronic heart failure patients was mediated by psychological and physiological symptoms. Relevance to Clinical Practice: It is important to design non‐pharmacological intervention plans for the enhancement of physical and psychological symptoms' management skills, to reduce the adverse impact of heart failure symptoms on quality of life. Reporting Method: Study methods and results reported in adherence to the STROBE checklist. No Patient or Public Contribution: No patients or members of the public were involved in the study. [ABSTRACT FROM AUTHOR]

Objective: Although inpatient treatment is highly effective for patients with bulimia nervosa (BN), some patients show a resurgence of symptoms and relapse after discharge. Therefore, the aim of this study is to evaluate the efficacy of a guided smartphone‐based aftercare intervention following inpatient treatment to support recovery. Method: 172 female patients with BN (DSM‐5: 307.51) will be randomized to receive a 16‐week smartphone‐based aftercare intervention (German version of 'Recovery Record') with therapist feedback as an add‐on element to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline (discharge, T0), during the intervention (after 4 weeks, T1), post‐intervention (after 16 weeks, T2) and at 6‐month follow‐up (T3). Primary outcome will be remission at T2. Moderator and mediator analyses will investigate for whom the aftercare intervention suits best and how it works. Conclusions: This is the first randomized controlled trial to examine a guided smartphone‐based aftercare intervention following inpatient treatment of patients with BN. We expect that this innovative aftercare intervention is highly accepted by the patients and that it has the potential to support recovery after inpatient treatment and thereby could contribute to improving aftercare for patients with BN. Highlights: There are several studies reporting relapse rates for patients with bulimia nervosa (BN) after having received remission or abstinence at the end of treatment.This is the first randomized controlled trial (RCT) to investigate the effects of a guided smartphone‐based aftercare following inpatient treatment of patients with BN.If this innovative aftercare intervention is accepted by the patients and supports recovery after inpatient treatment for patients with BN, it could contribute to improving aftercare for patients with BN. [ABSTRACT FROM AUTHOR]

The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019–2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N= 100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91–16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P <0.001), umbilical lines (aOR:1.85, P =0.03) and single rooms (aOR:3.63, P =0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats. [ABSTRACT FROM AUTHOR]

Introduction: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging. Materials and methods: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I. Results: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction. Conclusion: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals. [ABSTRACT FROM AUTHOR]

COVID-19, a systemic multi-organ disease resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to result in a wide array of disease outcomes, ranging from asymptomatic to fatal. Despite persistent progress, there is a continued need for more accurate determinants of disease outcomes, including post-acute symptoms after COVID-19. In this study, we characterised the serum metabolomic changes due to hospitalisation and COVID-19 disease progression by mapping the serum metabolomic trajectories of 71 newly hospitalised moderate and severe patients in their first week after hospitalisation. These 71 patients were spread out over three hospitals in Switzerland, enabling us to meta-analyse the metabolomic trajectories and filter consistently changing metabolites. Additionally, we investigated differential metabolite–metabolite trajectories between fatal, severe, and moderate disease outcomes to find prognostic markers of disease severity. We found drastic changes in serum metabolite concentrations for 448 out of the 901 metabolites. These results included markers of hospitalisation, such as environmental exposures, dietary changes, and altered drug administration, but also possible markers of physiological functioning, including carboxyethyl-GABA and fibrinopeptides, which might be prognostic for worsening lung injury. Possible markers of disease progression included altered urea cycle metabolites and metabolites of the tricarboxylic acid (TCA) cycle, indicating a SARS-CoV-2-induced reprogramming of the host metabolism. Glycerophosphorylcholine was identified as a potential marker of disease severity. Taken together, this study describes the metabolome-wide changes due to hospitalisation and COVID-19 disease progression. Moreover, we propose a wide range of novel potential biomarkers for monitoring COVID-19 disease course, both dependent and independent of the severity. [ABSTRACT FROM AUTHOR]

Background and purpose: Deep learning contouring (DLC) has the potential to decrease contouring time and variability of organ contours. This work evaluates the effectiveness of DLC for prostate and head and neck across four radiotherapy centres using a commercial system. Materials and methods: Computed tomography scans of 123 prostate and 310 head and neck patients were evaluated. Besides one head and neck model, generic DLC models were used. Contouring time using centres’ existing clinical methods and contour editing time after DLC were compared. Timing was evaluated using paired and non-paired studies. Commercial software or in-house scripts assessed dice similarity coefficient (DSC) and distance to agreement (DTA). One centre assessed head and neck inter-observer variability. Results: The mean contouring time saved for prostate structures using DLC compared to the existing clinical method was 5.9 ± 3.5 min. The best agreement was shown for the femoral heads (median DSC 0.92 ± 0.03, median DTA 1.5 ± 0.3 mm) and the worst for the rectum (median DSC 0.68 ± 0.04, median DTA 4.6 ± 0.6 mm). The mean contouring time saved for head and neck structures using DLC was 16.2 ± 8.6 min. For one centre there was no DLC time-saving compared to an atlas-based method. DLC contours reduced inter-observer variability compared to manual contours for the brainstem, left parotid gland and left submandibular gland. Conclusions: Generic prostate and head and neck DLC models can provide time-savings which can be assessed with paired or non-paired studies to integrate with clinical workload. Reducing inter-observer variability potential has been shown.

COVID-19, a systemic multi-organ disease resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to result in a wide array of disease outcomes, ranging from asymptomatic to fatal. Despite persistent progress, there is a continued need for more accurate determinants of disease outcomes, including post-acute symptoms after COVID-19. In this study, we characterised the serum metabolomic changes due to hospitalisation and COVID-19 disease progression by mapping the serum metabolomic trajectories of 71 newly hospitalised moderate and severe patients in their first week after hospitalisation. These 71 patients were spread out over three hospitals in Switzerland, enabling us to meta-analyse the metabolomic trajectories and filter consistently changing metabolites. Additionally, we investigated differential metabolite–metabolite trajectories between fatal, severe, and moderate disease outcomes to find prognostic markers of disease severity. We found drastic changes in serum metabolite concentrations for 448 out of the 901 metabolites. These results included markers of hospitalisation, such as environmental exposures, dietary changes, and altered drug administration, but also possible markers of physiological functioning, including carboxyethyl-GABA and fibrinopeptides, which might be prognostic for worsening lung injury. Possible markers of disease progression included altered urea cycle metabolites and metabolites of the tricarboxylic acid (TCA) cycle, indicating a SARS-CoV-2-induced reprogramming of the host metabolism. Glycerophosphorylcholine was identified as a potential marker of disease severity. Taken together, this study describes the metabolome-wide changes due to hospitalisation and COVID-19 disease progression. Moreover, we propose a wide range of novel potential biomarkers for monitoring COVID-19 disease course, both dependent and independent of the severity.

Necrotising fasciitis (NF) is a rapidly progressing fatal disease. Craniofacial necrotising fasciitis (CNF) is limited to the region above the mandibular margin, and early diagnosis is particularly difficult in the absence of related studies. Ten‐year data of patients with craniofacial infection were collected from four separate hospitals. Based on the diagnostic criteria, patients were classified into abscess and CNF. The risk factors for early diagnosis were analysed by comparing the two groups. Simple abscess was found in 176 patients, and CNF was detected in 25 patients. The risk factors associated with CNF include old age, presence of odontogenic infection, elevated white blood cell count (WBC), increased C‐reactive protein (CRP), high levels of creatinine (Cr) and glucose (Glu) and low levels of haemoglobin (Hb) and albumin (Alb). In addition, fever above 38°C and sinusitis at the time of admission and progressive sepsis after admission were also risk factors. Among the statistically significant risk factors, low Alb level showed the greatest association with CNF progression. Appropriate management of CNF via early diagnosis and extensive surgical intervention based on identified risk factors can reduce the mortality rate, complications and unnecessary medical expenses. Clinical question/level of evidence: Diagnostic, III. [ABSTRACT FROM AUTHOR]

Abstract Background Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC). Methods A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC). Results Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03). Conclusions A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol.

Supplemental Digital Content is available in the text Objectives: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. Background: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. Methods: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. Results: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July. Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM. The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months. During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. Conclusion: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status. Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the TANDEM trial is to evaluate whether a tailored, psychological cognitive behavioural approach intervention, which links into, and optimises the effects of routine pulmonary rehabilitation (PR), leads to a reduction in mild/moderate anxiety and/or depression in people with moderate, severe or very severe chronic obstructive pulmonary disease. Methods and design TANDEM is a multi-centre, two-arm, parallel group, pragmatic, individually randomised controlled, superiority trial including an internal pilot. Participants are randomised to receive either the intervention (a tailored psychological intervention plus usual care including referral to PR) or the control (usual care including referral to PR). The designed randomisation ratio is 1.25:1 in favour of the intervention. The multiple-primary outcomes are participant depression and anxiety at 6 months, measured using the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales. Results This article describes the statistical analysis plan (SAP) for the TANDEM trial. In particular, we describe the general analysis principles, how we will handle missing data, the primary and secondary outcomes and how these will be analysed, sensitivity analyses for the multiple-primary outcomes, and any other analyses and data summaries. The SAP was developed and published prior to completion of follow-up of the last participant. Trial registration ISRCTN registry ISRCTN59537391. Registered on 20 March 2017.

Background: Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC). Methods: A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC). Results: Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03). Conclusions: A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10–3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98–2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46). Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome. • A 12.5% 30-day fatality rate for Klebsiella pneumoniae bloodstream infections. • Klebsiella variicola was associated with increased 30-day mortality risk (aHR 1.86). • Global MDR-associated clones were common (25.0%) but mainly antimicrobial-sensitive. • Global MDR-associated clones were often (53.7%) community acquired. [ABSTRACT FROM AUTHOR]

Abstract Background Research involving brain imaging is important for understanding common brain diseases. Study endpoints can include features and measures derived from imaging modalities, providing a benchmark against which other phenotypical data can be assessed. In trials, imaging data provide objective evidence of beneficial and adverse outcomes. Multi-centre studies increase generalisability and statistical power. However, there is a lack of practical guidelines for the set-up and conduct of large neuroimaging studies. Methods We address this deficit by describing aspects of study design and other essential practical considerations that will help researchers avoid common pitfalls and data loss. Results The recommendations are grouped into seven categories: (1) planning, (2) defining the imaging endpoints, developing an imaging manual and managing the workflow, (3) performing a dummy run and testing the analysis methods, (4) acquiring the scans, (5) anonymising and transferring the data, (6) monitoring quality, and (7) using structured data and sharing data. Conclusions Implementing these steps will lead to valuable and usable data and help to avoid imaging data wastage.

Background: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China. Methods: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated. Findings: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (−8.8 days, 95%CI −9.7, −7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (−2.35 days, 95%CI −3.65, −1.06) compared to interferon-beta-1b monotherapy. Interpretation: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients. Funding: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.

Introduction: We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5–3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. Methods: Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and Discussion: Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001–0.005 ppm (χ) and 0.0005–0.001 ms−1 (R2*). For χ this is 2.1–4.8 fold better than 3T reports, and 1.1–3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. Conclusion: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

During the coronavirus disease-2019 (COVID-19) pandemic there were several barriers to treatment access and medication adherence in rheumatoid arthritis (RA) patients. There is no information regarding the RA patient health status in Egypt during the COVID-19. Thus,the aim of this work was to study the impact of the pandemic on RA patients through a patient-reported questionnaire and to determine the influence of gender, geographic regions. This multi-centre study initiated by the Egyptian College of Rheumatology (ECR) was conducted on 1037 RA patients attending rheumatology clinics from 10 governorates. The questionnaire provided covered socio-demographic data, health/disease status, information/knowledge about COVID-19 and medical/family history of the infection. Patients mean age was 44.2 ± 12.3 years;855 females and 182 males; 539(52%) from rural and 497(48%) from urban areas. 41.8% reported a striking difficulty to obtain hydroxychloroquine during the pandemic. The majority (70%) considered maintaining a regular visit to the rheumatologist in addition to remote contact mainly by phone (44.4%) or via WhatsApp (33.1%), in particular among male and urban patients. Urban patients were more likely to be infected by COVID-19 (12.9% vs 6.2%; p < 0.0001) than rural. Northern cities had more patients with suspected COVID-19 (13.9% vs 6.1%; p < 0.0001); was significantly associated with more disease flares (30.8% vs 5.8%) with subsequent change in the RA treatment (20.9% vs 6.4%; p < 0.0001). Patients with RA faced remarkable difficulty to obtain their medications with subsequent change in their disease status. The challenges of the pandemic have hastened changes in the way we deliver health care. [ABSTRACT FROM AUTHOR]

Background: Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. Methods: Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. Results: FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms. Conclusions: This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria. [ABSTRACT FROM AUTHOR]

Aims: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation., Methods and Results: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively., Conclusion: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy., Competing Interests: Conflict of interest: N.S.N. is co-founder of Lipid Tools. M.A., U.H., J.K.M., and J.P.E. are employees of Cleerly Inc. A.D.C. reports grant support from GW Heart and Vascular Institute, equity in Cleerly, Inc., and consulting with Siemens Healthineers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP ( n =6 453, 93.6%) or AP ( n =440, 6.4%) receiving initial imatinib ( n =4 906, 71.2%), nilotinib ( n =1 157, 16.8%), dasatinib ( n =298, 4.3%) or flumatinib ( n =532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n =1 055, 15.3%), intolerance ( n =248, 3.6%), pursuit of better efficacy ( n =168, 2.4%), economic or other reasons ( n =110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P <0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P =0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Background: Survivors of critical illness have significant psychopathological comorbidity. The treatments offered by primary health care professionals to affected patients are unstudied.Aim: To report the psychological interventions after GPs received notification of patients who showed severe symptoms of anxiety, depression or Post-Traumatic Stress Disorder.Methods: Design: Multi-centre prospective cohort sub-study of the ICON study.Setting: NHS primary care in the United Kingdom.Participants: Adult patients, November 2006-October 2010 who had received at least 24 h of intensive care, where the general practitioner recorded notification that the patient had reported severe symptoms or caseness using the Hospital Anxiety and Depression Scale (HADS) or the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C).Interventions: We notified general practitioners (GPs) by post if a patient reported severe symptoms or caseness and sent a postal questionnaire to determine interventions after notification.Main Outcome Measure: Primary or secondary healthcare interventions instigated by general practitioners following notification of a patient's caseness.Results: Of the 11,726 patients, sent questionnaire packs containing HADS and PCL-C, 4361 (37%) responded. A notification of severe symptoms was sent to their GP in 25% (1112) of cases. Of notified GPs, 65% (725) responded to our postal questionnaire. Of these 37% (266) had no record of receipt of the original notification. Of the 459 patients where GPs had record of notification (the study group for this analysis), 21% (98) had pre-existing psychopathology. Of those without a pre-existing diagnosis 45% (162) received further psychological assessment or treatment. GP screening or follow-up alone occurred in 18% (64) whilst 27% (98) were referred to mental health services or received drug therapy following notification.Conclusions: Postal questionnaire identifies a burden of psychopathology in survivors of critical illness that have otherwise gone undiagnosed following discharge from an intensive care unit (ICU). After being alerted to the presence of psychological symptoms, GPs instigate treatment in 27% and augmented surveillance in 18% of cases.Trial Registration: ISRCTN69112866 (assigned 02/05/2006). [ABSTRACT FROM AUTHOR]

Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low. [ABSTRACT FROM AUTHOR]

• Creation of manual plans is labor intensive with quality depending on planner. • A novel genetic optimization (GPS) for VMAT auto-planning is presented. • GPS was tested without centre-specific configuration. • Validation with ten centres, including in total 100 patients is presented. The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D 15% and D mean were reduced by 8.1% and 17.9%, bladder D 25% and D mean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable. A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning. [ABSTRACT FROM AUTHOR]

The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network was formed to build capacity and infrastructure for high‐quality musculoskeletal clinical trials in our region. The purpose of this paper is to describe the steps taken in its formation to help others interested in establishing similar networks. In particular, we describe the steps taken to form the collaboration and our progress in achieving our vision and mission. Our aim is to focus on trials of highest importance and quality to provide definitive answers to the most pressing questions in our field. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Odontogenic tumors originate from neoplastic transformation of the remnants of tooth forming apparatus. There are varying degrees of inductive interactions between odontogenic ectomesenchyme and epithelium during odontogenesis, leading to lesions that vary from benign to malignant. Malignant odontogenic tumours (MOTs) are very rare and are classified according embryonic tissue of origin. Recently, there has been a few changes to the classification of MOTs according to the World Health Organization's (WHO) classification in 2017. This study aims to evaluate and reclassify MOTs, using a multi-centre approach in some major tertiary dental hospitals in Nigeria. METHODS: this study reviewed the clinicopathological data on 63 cases of MOT diagnosed over 25 years in five major tertiary dental hospitals in Nigeria. All MOT cases were reclassified according to the recent revision to the 2017 WHO classification of odontogenic tumours. RESULTS: from a total of 10,446 biopsies of oral and jaw lesions seen at the 5 study centres over the 25-year study period, 2199 (21.05%) cases were found to be odontogenic tumours (OTs), of which 63 were MOT. MOTs constituted (0.60%) of the total biopsy cases and 2.86% of OTs. Odontogenic carcinomas presented with a mean age higher than odontogenic sarcomas. According to our 2017 WHO reclassification of MOTs, odontogenic carcinomas, ameloblastic carcinomas and primary intraosseous carcinomas were found to be the top three lesions, respectively. Carcinosarcomas were found to be extremely rare. CONCLUSION: using a multi-centre approach is a robust way to reduce diagnostic challenges associated with rare maxillofacial lesions such as MOTs.

Background: The multiple sclerosis (MS) prodrome is poorly characterized. Objective: To phenotype the MS prodrome via health care encounters. Methods: Using data from a population-based cohort study linking administrative and clinical data in four Canadian provinces, we compared physician and hospital encounters and prescriptions filled (via International Classification of Diseases chapters, physician specialty or drug classes) for MS subjects in the 5 years before the first demyelinating claim in an administrative cohort or the clinical symptom onset in an MS clinic-derived cohort, to age-, sex- and geographically matched controls. Rate ratios (RRs), 95% confidence intervals (95% CIs) and proportions were estimated. Results: The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous (RR (range) = 2.31; 95% CI: 1.05–5.10 to 4.75; 95% CI: 3.11–7.25), sensory (RR (range) = 1.40; 95% CI: 1.34–1.46 to 2.28; 95% CI: 1.72–3.02), musculoskeletal (RR (range) = 1.19; 95% CI: 1.07–1.33 to 1.70; 95% CI: 1.57–1.85) and genito-urinary systems (RR (range) = 1.17; 95% CI: 1.05–1.30 to 1.59; 95% CI: 1.48–1.70). Cases had more psychiatrist and urologist encounters (RR (range) = 1.48; 95% CI: 1.36–1.62 to 1.80; 95% CI: 1.61–2.01), and higher proportions of musculoskeletal, genito-urinary or hormonal-related prescriptions (1.1–1.5 times higher, all p < 0.02). However, cases had fewer pregnancy-related encounters than controls (RR = 0.78; 95% CI: 0.71–0.86 to 0.88; 95% CI: 0.84–0.92). Conclusion: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible. [ABSTRACT FROM AUTHOR]

Background: The inter‐jurisdictional National Mutual Acceptance (NMA) scheme for Human Research Ethics Committee (HREC) approvals of human research is designed to reduce the reported delays and costs of ethical review. Introduction of the NMA set forth an uncoupling of the ethics and governance review processes, permitting a single ethical review for multiple sites, while continuing separate governance review for each centre covering financial and operational aspects of the research project. Aim: To compare the time required to gain ethics and governance approvals in Australia for a non‐interventional investigator‐led study from December 2015 to approval times for an earlier pre‐NMA study utilising a similar study design and study sites and evaluate the effect that the NMA has had on total approval time for non‐interventional multi‐centre projects. Methods: We recorded the time taken to obtain ethics and governance approval at 16 sites for our nationwide low‐risk non‐interventional study looking at the prevalence and aetiology of non‐tuberculous mycobacterial infection in people with cystic fibrosis in Australia. Results: Applications were submitted to three hospitals and one university HREC to conduct our study at 16 hospital sites, HREC approval took from 16 to 79 days (median 28). Subsequent site‐specific governance approval at 15 hospital sites took 23–225 days (median 83). The entire process of gaining ethical and governance approval to conduct the study at 16 sites took 24 months at an estimated cost of AU$56000 (US$ 42 000). Conclusion: Lengthy governance approval processes negate benefits gained from centralised ethics review under the NMA. [ABSTRACT FROM AUTHOR]

Introduction: odontogenic tumors originate from neoplastic transformation of the remnants of tooth forming apparatus. There are varying degrees of inductive interactions between odontogenic ectomesenchyme and epithelium during odontogenesis, leading to lesions that vary from benign to malignant. Malignant odontogenic tumours (MOTs) are very rare and are classified according to embryonic tissue of origin. Recently, there has been a few changes to the classification of MOTs according to the World Health Organization's (WHO) classification in 2017. This study aims to evaluate and reclassify MOTs, using a multi-centre approach in some major tertiary dental hospitals in Nigeria. Methods: this study reviewed the clinicopathological data on 63 cases of MOT diagnosed over 25 years in five major tertiary dental hospitals in Nigeria. All MOT cases were reclassified according to the recent revision to the 2017 WHO classification of odontogenic tumours. Results: from a total of 10,446 biopsies of oral and jaw lesions seen at the 5 study centres over the 25-year study period, 2199 (21.05%) cases were found to be odontogenic tumours (OTs), of which 63 were MOT. MOTs constituted 0.60% of the total biopsy cases and 2.86% of OTs. Odontogenic carcinomas presented with a mean age higher than odontogenic sarcomas. According to our 2017 WHO reclassification of MOTs, odontogenic carcinomas, ameloblastic carcinomas and primary intraosseous carcinomas were found to be the top three lesions, respectively. Carcinosarcomas were found to be extremely rare. Conclusion: using a multi-centre approach is a robust way to reduce diagnostic challenges associated with rare maxillofacial lesions such as MOTs. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Validated biomarkers are needed to monitor the effects of immune intervention in individuals with type 1 diabetes. Despite their importance, few options exist for monitoring antigen-specific T cells. Previous reports described a combinatorial approach that enables the simultaneous detection and quantification of multiple islet-specific CD8+ T cell populations. Here, we set out to evaluate the performance of a combinatorial HLA-A2 multimer assay in a multi-centre setting.Methods: The combinatorial HLA-A2 multimer assay was applied in five participating centres using centralised reagents and blinded replicate samples. In preliminary experiments, samples from healthy donors were analysed using recall antigen multimers. In subsequent experiments, samples from healthy donors and individuals with type 1 diabetes were analysed using beta cell antigen and recall antigen multimers.Results: The combinatorial assay was successfully implemented in each participating centre, with CVs between replicate samples that indicated good reproducibility for viral epitopes (mean %CV = 33.8). For beta cell epitopes, the assay was very effective in a single-centre setting (mean %CV = 18.4), but showed sixfold greater variability across multi-centre replicates (mean %CV = 119). In general, beta cell antigen-specific CD8+ T cells were detected more commonly in individuals with type 1 diabetes than in healthy donors. Furthermore, CD8+ T cells recognising HLA-A2-restricted insulin and glutamate decarboxylase epitopes were found to occur at higher frequencies in individuals with type 1 diabetes than in healthy donors.Conclusions/interpretation: Our results suggest that, although combinatorial multimer assays are challenging, they can be implemented in multiple laboratories, providing relevant T cell frequency measurements. Assay reproducibility was notably higher in the single-centre setting, suggesting that biomarker analysis of clinical trial samples would be most successful when assays are performed in a single laboratory. Technical improvements, including further standardisation of cytometry platforms, will likely be necessary to reduce assay variability in the multi-centre setting. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. METHODS: in this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). RESULTS: of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). CONCLUSION: a multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Introduction: Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. Methods: in this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Results: Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). Conclusion: A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa. [ABSTRACT FROM AUTHOR]

Background: Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. Methods: The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, openlabel, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. Discussion: The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. [ABSTRACT FROM AUTHOR]

Density assessment and lesion localization in breast MRI require accurate segmentation of breast tissues. A fast, computerized algorithm for volumetric breast segmentation, suitable for multi-centre data, has been developed, employing 3D bias-corrected fuzzy c-means clustering and morphological operations. The full breast extent is determined on T1-weighted images without prior information concerning breast anatomy. Left and right breasts are identified separately using automatic detection of the midsternum. Statistical analysis of breast volumes from eighty-two women scanned in a UK multi-centre study of MRI screening shows that the segmentation algorithm performs well when compared with manually corrected segmentation, with high relative overlap (RO), high true-positive volume fraction (TPVF) and low false-positive volume fraction (FPVF), and has an overall performance of RO 0.94 ± 0.05, TPVF 0.97 ± 0.03 and FPVF 0.04 ± 0.06, respectively (training: 0.93 ± 0.05, 0.97 ± 0.03 and 0.04 ± 0.06; test: 0.94 ± 0.05, 0.98 ± 0.02 and 0.05 ± 0.07). [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the level of knowledge on pulse oximetry among nurses. Understanding this is important because insufficient knowledge can lead to misinterpretation of pulse oximetry readings and consequently compromise patient safety. Research methodology: The study was cross-sectional and included a sample of 198 nurses. A modified questionnaire by Kiekkas et al. was used as the research tool. Setting: Intensive care units, anaesthesiology and emergency departments in two tertiary health care institutions in Serbia. Main outcome measures: Principles of pulse oximeter function and conditions that can affect accuracy and reliability of pulse oximetry readings. Results: The lower percentage of correct responses about principles of pulse oximetry function was found in items related with the alarm reliability and understanding technical limitations. The factors that might affect pulse oximetry readings which were not identified by the nurses at a satisfactory level were the body position and specific kinds of ambient light. The mean scores of knowledge level were significantly different regarding departments (p = 0.015). Conclusion: Since this study revealed a lower level of knowledge in some aspects of pulse oximetry, it can be concluded that the generally firm belief that "experience is everything" can be challenged. This fact is important for the quality of health care and the patient's safety. [ABSTRACT FROM AUTHOR]

This multi-centre, randomised study included 47 Russian cities, 350 internists, and 1050 patients with uncontrolled treated arterial hypertension (AH). The study aimed at multiple risk factor correction, to reduce total cardiovascular risk level, assessed by the SCORE scale. Antihypertensive therapy was combined with educating education in Health Schools, targeting such risk factors as dyslipidemia, smoking, and overweight or obesity. The control group did not receive any educational intervention. For the first time, the electronic SCORE version was used in a clinical trial as a motivational tool to reduce total cardiovascular risk. The potential effectiveness of this instrument in clinical settings was evaluated.

Background Nurse-led care is well established in Rheumatology in the UK and provides follow-up care to people with inflammatory arthritis including treatment, monitoring, patient education and psychosocial support. Aim The aim of this study is to compare and contrast interactional style with patients in physician-led and nurse-led Rheumatology clinics. Design A multi-centre mixed methods approach was adopted. Settings Nine UK Rheumatology out-patient clinics were observed and audio-recorded May 2009–April 2010. Participants Eighteen practitioners agreed to participate in clinic audio-recordings, researcher observations, and note-taking. Of 9 nurse specialists, 8 were female and 5 of 9 physicians were female. Eight practitioners in each group took part in audio-recorded post-clinic interviews. All patients on the clinic list for those practitioners were invited to participate and 107 were consented and observed. In the nurse specialist cohort 46% were female; 71% had a diagnosis of Rheumatoid Arthritis (RA). The physician cohort comprised 31% female; 40% with RA and 16% unconfirmed diagnosis. Nineteen (18%) of the patients observed were approached for an audio-recorded telephone interview and 15 participated (4 male, 11 female). Methods Forty-four nurse specialist and 63 physician consultations with patients were recorded. Roter's Interactional Analysis System (RIAS) was used to code this data. Thirty-one semi-structured interviews were conducted (16 practitioner, 15 patients) within 24 h of observed consultations and were analyzed using thematic analysis. Results RIAS results illuminated differences between practitioners that can be classified as ‘socio-emotional’ versus ‘task-focussed’. Specifically, nurse specialists and their patients engaged significantly more in the socio-emotional activity of ‘building a relationship’. Across practitioners, the greatest proportion of ‘patient initiations’ were in ‘giving medical information’ and reflected what patients wanted the practitioner to know rather than giving insight into what patients wanted to know from practitioners. Interviews revealed that continuity of practitioner was highly valued by patients as offering the benefits of an established relationship and of emotional support beyond that of the clinical encounter. This fostered familiarity not only with their particular medical history, but also their individual personal circumstances, and this encouraged patient participation. In contrast, practitioners (mis)perceived waiting times to have a greater impact on patient satisfaction. However, practitioner interviews also revealed that clinic structure is often outside of the practitioner control and can undermine the possibility of maintaining patient–practitioner continuity. Conclusions This research enhances understanding of nurse specialist consultation styles in Rheumatology, specifically the value of their socio-emotional communication skills to enhance patient participation. [ABSTRACT FROM AUTHOR]

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice-water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub-regions. A mixed effect model was used to measure the intra- and inter-scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra- and inter-scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra-scanner CV of 8.4% and inter-scanner CV of 24.8%. No major difference in the inter-scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra-scanner reproducibility, with the inter-scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter-scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi-centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

During the last two decades there has been an increasing interest in cardiac resynchronization therapy (CRT) in patients with heart failure. Major randomized clinical trials which tested the effectiveness of CRT included patients based on electrocardiographic (ECG) criteria amongst other features. However, there is an assumption that mechanical synchrony, as may be assessed by echocardiography, is the underlying mechanism that improves left ventricular function and finally the clinical outcome. Large multi-centre trials have failed to prove the usefulness of echocardiography in both selection of patients for CRT and identification of non-responders. On the contrary smaller trials from centres where there is high expertise in echo techniques have demonstrated that mechanical dyssynchrony can be assessed by echocardiography and can actually predict the response to CRT in a better way than traditional ECG criteria. In this manuscript, we have analysed current evidence from published data and attempted to provide insight to the field of cardiac dyssynchrony as assessed with echocardiography. [ABSTRACT FROM AUTHOR]