Periodontal disease prevalence and oral hygiene status of adults with cystic fibrosis: A case-control study.

AIM: To investigate the prevalence of gingivitis and periodontitis, and the oral hygiene status of adults with cystic fibrosis (CF) in the Republic of Ireland. MATERIALS AND METHODS: A case-control study in the form of a clinical examination of 92 adults with a diagnosis of CF was carried out in the adult CF unit in Cork University Hospital. A 40-item questionnaire was used to capture socio-demographic variables and medical and dental information. Two calibrated examiners carried out a periodontal assessment on participants, using the WHO-recommended CPI-modified index, and oral hygiene status was measured using the Greene-Vermillion index. The results were compared with a population-based control group of similar socio-demographic profile. RESULTS: Oral hygiene levels (plaque and calculus) were significantly worse in people with CF, with a median plaque index of 0.83 (interquartile range [IQR] 0.333-1.542) in the CF group compared with 0.5 (IQR 0.167-0.667) in the non-CF group. Calculus index in the CF group was 0.33 (IQR 0.17-0.83) compared with 0.33 (IQR 0.125-0.33) in the non-CF group. However, periodontal disease levels were significantly lower in the CF group. Gingivitis (bleeding on probing ≥ 10% sites) was seen in 67.4% of the CF group, compared with 83.7% of the non-CF group, OR 0.365 (95% confidence interval [CI] 0.181-0.736), relative risk (RR) 0.779 (95% CI 0.655-0.928). Mild periodontitis (periodontal probing depth [PPD] < 5 mm) was seen in 15.2% of the CF group, compared with 31.5% of the non-CF group, OR 0.390 (CI 0.190-0.800), RR 0.483 (95% CI 0.273-0.852). Severe periodontitis (PPD ≥ 6 mm) was seen in 0% of the CF group, compared with 9.8% of the non-CF group. There was a tendency, albeit non-significant, towards reduced periodontitis in PWCF who regularly took antibiotics, particularly azithromycin. CONCLUSIONS: In this study, adults with CF had poor oral hygiene practices, with high levels of plaque and calculus. Despite this finding, adults with CF had lower levels of clinical gingivitis and periodontitis than seen in a non-CF control group. Further study is required to examine the causes of this phenomenon.

Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial.

Rationale: Clinical trials have shown that use of elexacaftor/tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. Objectives: RECOVER is a real-world study designed to measure the impact of ETI in people with CF. The primary endpoints were lung clearance (lung clearance index; LCI2.5) and FEV1. Secondary endpoints included spirometry-controlled chest computed tomography (CT) scores. Methods: The study was conducted in seven sites in Ireland and the United Kingdom. Participants ages 12 years and older who were homozygous for the F508del mutation (F508del/F508del) or heterozygous for F508del and a minimum-function mutation (F508del/MF) were recruited before starting ETI and were followed up over 12 months. LCI2.5 was measured using nitrogen multiple breath washout (MBW) at baseline and at 6 and 12 months. Spirometry was performed as per the criteria of the American Thoracic Society and the European Respiratory Society. Spirometry-controlled chest CT scans were performed at baseline and at 12 months. CT scans were scored using the Perth Rotterdam Annotated Grid Morphometric Analysis (PRAGMA) system. Other outcome measures include weight, height, Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R), and sweat chloride. Measurements and Main Results: One hundred seventeen people with CF ages 12 and older were recruited to the study. Significant improvements were seen in LCI scores (-2.5; 95% confidence interval [CI], -3.0, -2.0) and in the percents predicted for FEV1 (8.9; 95% CI, 7.0, 10.9), FVC (6.6; 95% CI, 4.9, 8.3), and forced expiratory flow between 25% and 75% of expired volume (12.4; 95% CI, 7.8, 17.0). Overall PRAGMA-CF scores reflecting airway disease improved significantly (-3.46; 95% CI, -5.23, -1.69). Scores for trapped air, mucus plugging, and bronchial wall thickening improved significantly, but bronchiectasis scores did not. Sweat chloride levels decreased in both F508del/F508del (-43.1; 95% CI, -47.4, -38.9) and F508del/MF (-42.8; 95% CI, -48.5, -37.2) groups. Scores on the Respiratory Domain of the CFQ-R improved by 14.2 points (95% CI, 11.3, 17.2). At 1 year, sweat chloride levels were significantly lower for the F508del/F508del group compared with scores for the F508del/MF group (33.93 vs. 53.36, P < 0.001). Conclusions: ETI is associated with substantial improvements in LCI2.5, spirometry, and PRAGMA-CF CT scores in people with CF ages 12 years and older. ETI led to improved nutrition and quality of life. People in the F508del/F508del group had significantly lower sweat chloride on ETI treatment compared with the F508del/MF group. Clinical trial registered with www.clinicaltrials.gov (NCT04602468).

The Application of High-Resolution, Embedded Fibre Optic (FO) Sensing for Large-Diameter Composite Steel/Plastic Pipeline Performance under Dynamic Transport Loads.

Distributed optical fibre sensing (DOFS)-based strain measurement systems are now routinely deployed across infrastructure health monitoring applications. However, there are still practical performance and measurement issues associated with the fibre's attachment method, particularly with thermoplastic pipeline materials (e.g., high-density polyethylene, HDPE) and adhesive affixment methods. In this paper, we introduce a new optical fibre installation method that utilises a hot-weld encapsulation approach that fully embeds the fibre onto the pipeline's plastic surface. We describe the development, application and benefits of the new embedment approach (as compared to adhesive methods) and illustrate its practical performance via a full-scale, real-world, dynamic loading trial undertaken on a 1.8 m diameter, 6.4 m long stormwater pipeline structure constructed from composite spiral-wound, steel-reinforced, HDPE pipe. The optical frequency domain reflectometry (OFDR)-based strain results show how the new method improves strain transference and dynamic measurement performance and how the data can be easily interpreted, in a practical context, without the need for complex strain transfer functions. Through the different performance tests, based on UK rail-road network transport loading conditions, we also show how centimetre- to metre-scale strain variations can be clearly resolved at the frequencies and levels consistent with transport- and construction-based, buried infrastructure loading scenarios.

Patient attrition in Molecular Tumour Boards: a systematic review.

BACKGROUND: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment. METHODS: A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 51 papers were reviewed spanning a 6-year period from 11 different countries. RESULTS: In total, 20% of patients received treatment through the MTB process. Of those that did not receive treatment, the main reasons were no mutations identified (27%), no actionable mutations (22%) and clinical deterioration (15%). However, data were often incomplete due to inconsistent reporting of MTBs with only 55% reporting on patients having no mutations, 55% reporting on the presence of actionable mutations with no treatment options and 59% reporting on clinical deterioration. DISCUSSION: As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis - A cross sectional study.

OBJECTIVES: Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. METHODS: A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. RESULTS: 64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. CONCLUSION: In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. CLINICAL SIGNIFICANCE: Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

PROACT 2.0: A new open-source tool to improve patient-doctor communication in clinical trials.

The use of Digital Healthcare Products is leading to significant improvements in clinical practice. Herein, we discuss the development of PROACT 2.0 (Patient Reported Opinions About Clinical Tolerability v2.0), a novel open-source mobile and web application developed at Fondazione IRCCS Istituto Nazionale Tumori in Milan. It was developed in collaboration with The Christie, Manchester, in the context of work package 2 of the UpSMART Accelerator project, involving a consortium of referral cancer centers from the UK, Spain and Italy. PROACT 2.0 enhances communication between patients and healthcare providers in cancer clinical trials, allowing patients to report adverse events and side effects, and healthcare teams to collect valuable patient-reported outcome measures for treatment management. PROACT 2.0 supports text, audio, and video messaging, offering a secure, non-urgent communication channel that integrates with, or replaces, traditional methods. Its user-friendly and multilingual interface provides a new route for patient engagement and streamlines the handling of logistical information. Positive feedback from initial testing warrants future enhancements for broader applicability in cancer research and treatment.

Digital ECMT Cancer Trial Matching Tool: an Open Source Research Application to Support Oncologists in the Identification of Precision Medicine Clinical Trials.

PURPOSE: Matching patients with cancer to precision medicine clinical trials on the basis of their tumor genotype has the potential to improve outcomes for patients who have exhausted standard-of-care treatment options. However, the matching process presents a substantial challenge because of the number of clinical trials available. We describe a free, open source research tool designed to extract relevant trial information to support oncologists in the matching process, and we illustrate its utility with recent case studies of patients who were matched to trials using this tool. METHODS: Trial records are sourced from ClinicalTrials.gov and indexed using natural language processing techniques, including named entity recognition, term normalization, and relationship extraction. Relationships between trials and genetic alterations are assigned scores on the basis of a rule-based system. All data are updated daily. A user interface is provided via R Shiny app. RESULTS: An instance of the trial match tool, configured for UK clinical trials, is hosted by the digital Experimental Cancer Medicine Team (see link in Data Sharing Statement). Users select the relevant cancer type and genetic alteration(s). Matching studies are ranked according to the score assigned for the selected genetic alterations. Results may be downloaded and attached to the patient's health record if desired. The tool is currently being used to support the ongoing TARGET National study, which aims to match up to 6,000 patients to early phase clinical trials. We present three case studies that exemplify relationships between genetic alterations and studies. CONCLUSION: With increasing numbers of precision medicine treatments and as comprehensive molecular profiling of tumor samples becomes more common, decision support tools are likely to become increasingly important. This work represents an important step toward the development and wider implementation of such systems.

Telehealth in Cystic Fibrosis. A systematic review incorporating a novel scoring system and expert weighting to identify a 'top 10 manuscripts' to inform future best practices implementation.

The ongoing development and integration of telehealth within CF care has been accelerated in response to the Covid-19 pandemic, with many centres publishing their experiences. Now, as the restrictions of the pandemic ease, the use of telehealth appears to be waning, with many centres returning to routine traditional face-to-face services. For most, telehealth is not integrated into clinical care models, and there is a lack of guidance on how to integrate such a service into clinical care. The aims of this systematic review were to first identify manuscripts which may inform best CF telehealth practices, and second, to analyse these finding to determine how the CF community may use telehealth to improve care for patients, families, and Multidisciplinary Teams into the future. To achieve this, the PRISMA review methodology was utilised, in combination with a modified novel scoring system that consolidates expert weighting from key CF stakeholders, allowing for the manuscripts to be placed in a hierarchy in accordance with their scientific robustness. From the 39 found manuscripts, the top ten are presented and further analysed. The top ten manuscripts are exemplars of where telehealth is used effectively within CF care at this time, and demonstrate specific use cases of its potential best practices. However, there is a lack of guidance for implementation and clinical decision making, which remains an area for improvement. Thus, it is suggested that further work explores and provides guidance for standardised implementation into CF clinical practice.

Wave comparisons of clinical characteristics and outcomes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics.

OBJECTIVES: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. METHODS: This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202,012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as the dominant strain). RESULTS: Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p = 0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p = 0.308). CONCLUSIONS: The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new treatments and ongoing concern over new COVID-19 variants.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital.

OBJECTIVES: COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. DESIGN AND SETTING: This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. PARTICIPANTS: Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. RESULTS: The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%