2,293 results on '"Watson, C."'
Search Results
2. Volatile Anesthetic Intensive Care Unit Sedation: Comment.
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Rosenberg H, Watson C, and Larach MG
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- 2025
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3. The Uncoupling of Disease Activity from Joint Structural Progression in Patients with Rheumatoid Arthritis Treated with Filgotinib.
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Tanaka Y, Atsumi T, Aletaha D, Schulze-Koops H, Fukada H, Watson C, and Takeuchi T
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Introduction: While modern treatments can prevent progressive bone destruction in patients with rheumatoid arthritis (RA) achieving clinical remission, it is unclear whether residual clinical activity may cause or be associated with progressive joint damage. This post hoc analysis evaluated the association between clinical disease activity and structural progression in patients with RA treated with filgotinib (FIL) in FINCH 1 (NCT02889796)., Methods: Patients with RA and inadequate response to methotrexate (MTX) use were randomized 3:3:2:3 to FIL 200 mg (FIL200) or FIL 100 mg (FIL100) once daily, adalimumab 40 mg biweekly, or placebo, all with background MTX. We evaluated the change from baseline (CFB) in modified total Sharp score (mTSS), erosion score, and joint space narrowing score among patients achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8), low disease activity (LDA; 2.8 < CDAI ≤ 10), medium disease activity (MDA; 10 < CDAI ≤ 22), and high disease activity (HDA; CDAI > 22) at 24 weeks., Results: At week 24, the least squares (LS) mean CFB in mTSS was similarly low across treatments among patients who achieved CDAI remission (range 0.00-0.11) or LDA (n = 285 and 575, respectively). In patients with MDA and HDA (n = 471 and 157, respectively), smaller LS mean CFB in mTSS was seen in the FIL200 group vs. the placebo group (P < 0.05 for both)., Conclusions: RA clinical remission and LDA achievement were associated with suppressed progression of joint destruction over 24 weeks in all treatment groups. Only FIL200 significantly inhibited joint damage compared with placebo in patients with MDA or HDA, indicating an uncoupling of clinical disease activity and structural progression in patients receiving FIL200., Trial Registration: NCT02889796., Competing Interests: Declarations. Conflict of Interest: Yoshiya Tanaka received speaking fees and/or honoraria from AbbVie; Asahi Kasei; AstraZeneca; Astellas Pharma; Boehringer Ingelheim; Chugai; Daiichi Sankyo; Eisai; Eli Lilly; Gilead Sciences, Inc.; GSK; Pfizer; Taisho; and UCB, and received research grants from Chugai, Boehringer Ingelheim, and Taisho. Tatsuya Atsumi has accepted research grants and/or honoraria for meetings from AbbVie; Alexion Pharmaceuticals; Astellas Pharma; Bristol Myers Squibb; Chugai; Daiichi Sankyo; Eisai; Eli Lilly Japan; Gilead Sciences, Inc.; Mitsubishi-Tanabe; Otsuka Pharmaceutical; Pfizer; Takeda; and UCB Japan. Daniel Aletaha reports grants or research support from AbbVie, Merck Sharp & Dohme, Novartis, and Roche; serving as a consultant for Janssen; serving on a speakers bureau for Bristol Myers Squibb, Merck Sharp & Dohme, and UCB; and serving as a consultant and on a speakers bureau for AbbVie, Amgen, Celgene, Eli Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi. Hendrik Schulze-Koops has research grants from AbbVie and Novartis and has received honoraria for consultancies and/or speaking engagements from AbbVie; Amgen; Bristol Myers Squibb; Celgene; Celltrion; Chugai; Gilead Sciences, Inc.; Janssen; Eli Lilly; Merck Sharp & Dohme; Novartis-Sandoz; Pfizer; Roche; and Sanofi. Haruhiko Fukada is an employee of Gilead Sciences K.K. and a shareholder of Gilead Sciences, Inc. Chris Watson is an employee of Alfasigma, Bologna, Italy. Tsutomu Takeuchi reports receiving grant/research support from AbbVie, Asahi Kasei, Astellas Pharma, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan; serving as a consultant for Astellas Pharma, Chugai, and Eli Lilly Japan; and serving on a speakers bureau for AbbVie; Ayumi Pharmaceutical Corporation; Bristol Myers Squibb; Chugai; Daiichi Sankyo; Dainippon Sumitomo Pharma; Eisai; Eli Lilly Japan; Gilead Sciences, Inc.; Mitsubishi-Tanabe; Novartis; Pfizer Japan; and Sanofi. Yoshiya Tanaka and Tsutomu Takeuchi are editorial board members of Rheumatology and Therapy. Yoshiya Tanaka and Tsutomu Takeuchi were not involved in the selection of peer reviewers for the manuscript or any of the subsequent editorial decisions. Ethical Approval: The study protocols were reviewed and approved by all local institutional review boards or ethics committees of participating institutions. The studies were carried out in accordance with the Declaration of Helsinki and the International Council for Harmonisation Good Clinical Practice guidelines. All patients provided informed consent to participate. FINCH 1 was approved by the Advarra Central Institutional Review Board (reference 00000971)., (© 2024. The Author(s).)
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- 2025
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4. Surgery for Bronchiectasis: Experience and Outcomes at Starship Children's Hospital, Auckland, New Zealand.
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Watson C, Han DY, Byrnes CA, Hamill J, Morreau P, and Edwards E
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Background: Surgical management for bronchiectasis is uncommon. This study reviewed the experience of bronchiectasis surgery and subsequent outcomes at a tertiary paediatric centre over a 20 year period., Methods: Retrospective audit of children aged < 18 years who underwent bronchiectasis surgery at Starship Children's Hospital between 2001 and 2021. Cases were identified from clinical coding, with demographics, pre-operative investigations and outcomes obtained from clinical records., Results: Nineteen children (11 females, 42% Pasifika, 26% Māori and 26% New Zealand European) were included. Mean age of bronchiectasis diagnosis was 6.3 years (range 2.1-13.9 years) and mean age of surgery was 8.5 years (range 2.6-15.9 years). Indications for surgery included localised bronchiectasis (n = 7), main burden of multilobar disease in one lobe (n = 5) and persistent lobar collapse (n = 3). Pre-operative investigations included chest computerised tomography scan (68%), bronchoscopy (37%) and overnight oximetry (42%). One child underwent documented pre-operative clinical optimisation. For children with bronchiectasis < 5 years (n = 11), 81% demonstrated improved symptoms, 9% were unchanged and 9% deteriorated. All children with bronchiectasis > 5 years had symptomatic improvement. The mean number of daily symptoms decreased by 2.4 (p < 0.0001)., Conclusion: Lobectomy resulted in significant symptomatic improvement in 89% of children. However, pre-operative work-up was variable. The study highlights the importance of establishing a protocol for identification of children with bronchiectasis who would benefit from surgery and developing a consistent preparatory approach to ensure optimal and equitable outcomes., (© 2025 The Author(s). Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)
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- 2025
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5. The Sikkim flood of October 2023: Drivers, causes and impacts of a multihazard cascade.
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Sattar A, Cook KL, Rai SK, Berthier E, Allen S, Rinzin S, Van Wyk de Vries M, Haeberli W, Kushwaha P, Shugar DH, Emmer A, Haritashya UK, Frey H, Rao P, Gurudin KSK, Rai P, Rajak R, Hossain F, Huggel C, Mergili M, Azam MF, Gascoin S, Carrivick JL, Bell LE, Ranjan RK, Rashid I, Kulkarni AV, Petley D, Schwanghart W, Watson CS, Islam N, Gupta MD, Lane SN, and Bhat SY
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On 3 October 2023, a multihazard cascade in the Sikkim Himalaya, India, was triggered by 14.7 million m
3 of frozen lateral moraine collapsing into South Lhonak Lake, generating an ~20 m tsunami-like impact wave, breaching the moraine, and draining ~50 million m3 of water. The ensuing Glacial Lake Outburst Flood (GLOF) eroded ~270 million m3 of sediment, which overwhelmed infrastructure, including hydropower installations along the Teesta River. The physical scale and human and economic impact of this event prompts urgent reflection on the role of climate change and human activities in exacerbating such disasters. Insights into multihazard evolution are pivotal for informing policy development, enhancing Early Warning Systems (EWS), and spurring paradigm shifts in GLOF risk management strategies in the Himalaya and other mountain environments.- Published
- 2025
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6. Using machine learning to forecast peak health care service demand in real-time during the 2022-23 winter season: A pilot in England, UK.
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Morbey RA, Todkill D, Moura P, Tollinton L, Charlett A, Watson C, and Elliot AJ
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- Humans, England epidemiology, Pilot Projects, Child, Preschool, Infant, Health Services Needs and Demand, Machine Learning, Seasons, Respiratory Syncytial Virus Infections epidemiology, Forecasting methods
- Abstract
During winter months, there is increased pressure on health care systems in temperature climates due to seasonal increases in respiratory illnesses. Providing real-time short-term forecasts of the demand for health care services helps managers plan their services. During the Winter of 2022-23 we piloted a new forecasting pipeline, using existing surveillance indicators which are sensitive to increases in respiratory syncytial virus (RSV). Indicators including telehealth cough calls and emergency department (ED) bronchiolitis attendances, both in children under 5 years. We utilised machine learning techniques to train and select models that would best forecast the timing and intensity of peaks up to 28 days ahead. Forecast uncertainty was modelled usings a novel generalised additive model for location, scale and shape (gamlss) approach which enabled prediction intervals to vary according to the level of the forecast activity. The winter of 2022-23 was atypical because the demand for healthcare services in children was exceptionally high, due to RSV circulating in the community and increased concerns around invasive group A streptococcal (iGAS) infections. However, our short-term forecasts proved to be adaptive forecasting a new higher peak once the increasing demand due to iGAS started. Thus, we have demonstrated the utility of our approach, adding forecasts to existing surveillance systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Morbey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2025
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7. Patient safety is our business! Staff perspectives on implementing hospital falls prevention education.
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Loo CY, Coulter S, Watson C, Vaz S, Morris ME, Flicker L, Weselman T, and Hill AM
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- Humans, Hospitals, Female, Attitude of Health Personnel, Male, Personnel, Hospital education, Interviews as Topic, Qualitative Research, Accidental Falls prevention & control, Patient Safety, Focus Groups
- Abstract
Providing patients with falls prevention education reduces falls in hospitals, yet there is limited research on what influences successful implementation at the staff, ward and hospital levels. We engaged hospital-based health professionals to identify multi-level barriers and enablers to patient falls education that could influence the implementation of a Safe Recovery program. Purposive sampling was used to recruit hospital staff (n = 40) for focus groups and one-on-one interviews. Data were analysed using content analysis and categorized using a socio-ecological framework to understand the micro, meso and macro level influences of hospital falls prevention. We identified five overarching themes, on the barriers and enablers to implementation of the Safe Recovery program. The enablers to falls prevention education included sharing the responsibility to implement the program, setting clear goals for staff, showing the impact of delivering the program, involving family to reinforce the messaging, using falls champions to upskill staff and making the resources (video and booklet) readily available to patients at all times. Barriers included insufficient time for staff to deliver falls prevention education, lack of falls prevention training for staff during their clinical training, absence of standardized protocols and clinical guidelines across hospital settings and insufficient hospital marketing to promote the program. Using a systems thinking approach, this study showed that implementation requires more advocacy and support for patient falls prevention across different tiers of the hospital system to integrate into usual care., (© The Author(s) 2025. Published by Oxford University Press.)
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- 2025
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8. Normothermic regional and ex-situ perfusion reduces Postreperfusion syndrome in donation after circulatory death liver transplantation: a retrospective comparative study.
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Puttappa A, Gaurav R, Kakhandki V, Swift L, Fear C, Webster R, Radwan A, Mohammed M, Butler A, Klinck J, and Watson C
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In controlled donation after circulatory death (DCD) liver transplantation, ischemia-reperfusion injury is linked to post-reperfusion syndrome (PRS), acute kidney injury (AKI), and early allograft dysfunction (EAD). Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are techniques that mitigate ischemic injury and associated complications. In this single centre retrospective study, we compared early transplant outcomes of DCD livers undergoing direct procurement (DP) and static cold storage (DCD-DP-SCS), NRP procurement with SCS (DCD-NRP-SCS), or DP with NMP (DCD-DP-NMP). Two hundred and thirty-eight DCD liver recipients were evaluated, comprising 59 DCD-DP-SCS, 101 DCD-NRP-SCS, and 78 DCD-DP-NMP. Overall, the PRS incidence was 19%. DCD-DP-SCS had higher incidence of PRS (37%; P<0.001), AKI stage≥2 (47%; P=0.033), and increased Model for Early Allograft Function (MEAF) score (p<0.001). In adjusted multivariate analysis, recipient age (OR 1.10, 95%CI 1.05-1.17; P<0.001), and normothermic perfusion (DCD-NRP-SCS OR 0.16, 95%CI 0.06-0.39; P<0.001; DCD-DP-NMP OR 0.38, 95%CI 0.15-0.91; P=0.032) were significant predictors of PRS, which itself was associated with worse 5-year transplant survival (graft survival non-censored-to-death; HR 2.9, 95%CI 1.3-6.7; P=0.012). Compared to static cold storage alone, use of either NRP or NMP significantly reduced the incidence of PRS and AKI with better early graft function., (Copyright © 2025. Published by Elsevier Inc.)
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- 2025
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9. Using Inertial Measurement Units and Machine Learning to Classify Body Positions of Adults in a Hospital Bed.
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Becker E, Khaksar S, Booker H, Hill K, Ren Y, Tan T, Watson C, Wordsworth E, and Harrold M
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- Humans, Adult, Male, Female, Beds, Hospitals, Wrist physiology, Posture physiology, Monitoring, Physiologic methods, Monitoring, Physiologic instrumentation, Movement physiology, Machine Learning, Support Vector Machine
- Abstract
In hospitals, timely interventions can prevent avoidable clinical deterioration. Early recognition of deterioration is vital to stopping further decline. Measuring the way patients position themselves in bed and change their positions may signal when further assessment is necessary. While inertial measurement units (IMUs) have been used in health research, their use inside hospitals has been limited. This study explores the use of IMUs with machine learning to continuously capture, classify and visualise patient positions in hospital beds. The participants attended a data collection session in a simulated hospital bedspace and were asked to adopt nine positions. Movement data were captured using five IMU Xsens DOTs attached to the forehead, wrists and ankles. Support Vector Machine (SVM) and K-Nearest Neighbours classifiers were trained using five different combinations of sensors (e.g., right wrist only, right and left wrist) to determine body positions. Data from 30 participants were analysed. The highest accuracy (87.7%) was achieved by SVM using forehead and wrist sensors. Adding data from ankle sensors reduced the accuracy. To preserve patient privacy in a hospital setting, a 3D visualisation was developed in Unity, offering a non-identifiable representation of patient positions. This system could help clinicians monitor changes in position which may signal clinical deterioration.
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- 2025
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10. From the clinic to the wards, the evolution of penicillin allergy testing by non-allergists in a UK hospital.
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Watson C, Shah S, Hassan F, Suri T, Joseph D, Gopal Rao G, and McGregor A
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Competing Interests: Conflict of interest statement None declared.
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- 2025
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11. Improving the quality of self-collected swab specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in a clinical setting.
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McDonald M, Orser L, Watson C, Grayson MO, Trudeau D, McMillan K, and O'Byrne P
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Background: The practice of patient self-collected swab specimens for Neisseria gonorrhoeae and Chlamydia trachomatis is supported in the literature., Local Problem: Health care providers observed that patients sometimes performed their self-swabs incorrectly resulting in cancelled or invalid specimens., Methods: The clinic's outdated visual aids were replaced with new visual aids. The goal was to improve health care provider proficiency in providing the health teaching and to reduce the clinic's number of cancelled or invalid swab specimens. Staff evaluated the visual aids using an online pretest and post-test survey. The percentage of invalid swabs was calculated before and after project implementation., Intervention: The posters were designed and printed. In-person teaching on the project and using the new visual aids was provided., Results: There was no change in the reported proficiency of staff in providing health teaching for self-collected swab specimens. There was a reduction in staff observed self-swabbing errors. Three percent of rectal swabs were reported as invalid in the 2 weeks before project implementation, and 1.4% of rectal swabs were invalid in the 2 weeks after., Conclusions: Providing patient health teaching using verbal instructions combined with visual diagrams can improve patients' ability to retain health information., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2024 American Association of Nurse Practitioners.)
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- 2024
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12. 'Sometimes You Have No Choice but to Give Them Medication': Experiences of Nurses Caring for People With Auditory Hallucinations in an Acute Unit.
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McCluskey A, Watson C, Nugent L, O'Connor T, Moore Z, Molloy L, and Patton D
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- Humans, Female, Male, Adult, Interviews as Topic, Attitude of Health Personnel, Middle Aged, Qualitative Research, Nurse's Role psychology, Nursing Staff, Hospital psychology, Hallucinations nursing, Hallucinations psychology, Psychiatric Nursing methods
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The aim of this study was to explore psychiatric nurse's experiences of caring for people with auditory hallucinations in an acute unit. A qualitative study was conducted using thematic analysis. The study involved semi-structured interviews with 18 acute unit nurses all of whom provided interventions to patients with auditory hallucinations. Overall, participants identified their role in the management of risk within an acute unit, the importance of their therapeutic role and a perceived over-reliance on medication administration as a primary nursing intervention. These findings thus demonstrate the personal and professional conflict that nurses face when working in an acute unit with patients who experience auditory hallucinations. Nurses are in a prime position to provide effective interventions and assistance for people with auditory hallucinations in an acute unit. The findings of this study indicate that mental health nurses may require additional support and education to provide care in a truly recovery-based manner, with training in specific interventions and engagement skills for people who hear voices. Due to an unpredictable environment and sometimes high-risk workplace, nurses may also benefit from organisational assistance in this area., (© 2024 The Author(s). International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)
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- 2024
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13. Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.
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Reilly KM, Watson C, Ruddock M, Watt J, Kurth MJ, Fitzgerald P, Breathnach F, and Mone F
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- Humans, Female, Pregnancy, Heart Diseases etiology, Pre-Eclampsia physiopathology, Biomarkers blood
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While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia. Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)
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- 2024
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14. Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta-analysis.
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Savage P, Watson C, Coburn J, Cox B, Shahmohammadi M, Grieve D, and Dixon L
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- Humans, Ventricular Function, Left physiology, Ventricular Function, Left drug effects, Stroke Volume physiology, Sodium-Glucose Transporter 2 Inhibitors pharmacology, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Heart Failure drug therapy, Heart Failure physiopathology, Ventricular Remodeling drug effects, Ventricular Remodeling physiology
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Introduction: Several landmark randomized-controlled trials (RCTs) have demonstrated the efficacy of sodium-glucose co-transport 2 (SGLT2) inhibitors in reducing all-cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta-analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF., Methods: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration. Data interrogation of each major database including PubMed, EMBASE, MEDLINE and Cochrane Library was performed. RCTs evaluating HF patients >18 years comparing SGLT2 inhibitor versus placebo-control were included. Outcome measures included left ventricular end-diastolic volume and volume index (LVEDV/LVEDVi), left ventricular end-systolic volume and volume index (LVSDV/LVSDVi), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), left atrial volume index (LAVi) and left ventricular global longitudinal strain (LV GLS). Studies with an HF with preserved ejection fraction population were excluded from analysis of parameters, which would be significantly affected by baseline LVEF, such as volumes and LVEF. The mean difference and standard error were extracted from each study and a random effects model used pool the mean difference and standard error across studies. A pre-specified sub-group analysis was performed to stratify results according to imaging modality used (cardiac magnetic resonance imaging and echocardiography). This study is registered on PROSPERO: CRD42023482722., Results: Seven randomized, placebo-controlled trials in patients with HF comprising a total population of 657 patients were included. Overall LVEF of included studies ranged from 29 ± 8.0% to 55.5 ± 4.2%. In studies included in analysis of HFrEF parameters, baseline LVEF ranged from 29 ± 8% to 45.5 ± 12%. Pooled data demonstrated SGLT2 inhibition, compared with placebo control, resulted in significant improvements in mean difference of LVEDV [-11.62 ml (95% confidence interval, CI -17.90 to -5.25; z = 3.67, P = 0.0004)], LVEDVi [-6.08 ml (95% CI -9.96 to -2.20; z = 3.07; P = 0.002)], LVESV [-12.47 ml (95% CI -19.12 to -5.82; z = 3.68; P = 0.0002)], LVESVi [-6.02 ml (95% CI -10.34 to -1.70; z = 2.73; P = 0.006)], LVM [-9.77 g (95% CI -17.65 to -1.89; z = 2.43; P = 0.02)], LVMi (-3.52 g [95% CI -7.04 to 0.01; z = 1.96; P = 0.05)] and LVEF [+2.54 mL (95% CI 1.10 to 3.98; z = 3.62; P = 0.0005)]. No significant difference in GLS (n = 327) [+0.42% (95%CI -0.19 to 1.02; P = 0.18)] or LAVi [-3.25 ml (95% CI -8.20 to 1.69; z = 1.29; P = 0.20)] was noted., Conclusion: This meta-analysis provides additional data and insight into the effects of SGLT2 inhibition on reverse cardiac remodelling in patients with HF. Compared with placebo control, we found that treatment with a SGLT2 inhibitor produced significant improvements in several markers of reverse cardiac remodelling., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2024
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15. The revised remote area nurse model of consultation.
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Lenthall S, Knight S, Watson C, Byers L, Cameron F, Wright J, West S, West R, Ford M, Mobsby S, Pennington K, and Ajayi O
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- Humans, Australia, Models, Nursing, Remote Consultation, Rural Health Services organization & administration, Health Services, Indigenous organization & administration, Rural Nursing
- Abstract
Aim: The aim of this revision was to update the Remote Area Nurse (RAN) Model of Consultation (MoC) and was prompted by publication of the National Rural and Remote Nursing Generalist Framework (2013-2018), shifts in RAN workforce patterns, community health patterns and technology use., Context: Rural and remote residents face higher rates of hospitalisations, deaths and poorer access to health care with a significant burden of avoidable fatal conditions among Aboriginal and Torres Strait Islander peoples. Health care is mostly provided by RANs and Aboriginal and Torres Strait Islander Health Practitioners (ATSIHPs), addressing diverse health needs, a mobile population and navigating cross-cultural situations. Despite challenges such as clinician shortages, RANs manage a significant portion of non-emergency consultations. The RAN MoC was developed to ensure comprehensive, systematic and person-centred care and to mitigate risk to the client, the nurse and the health service., Approach: The 11 expert panel members, all authors, revised the RAN MoC through a series of Microsoft Teams meetings, one face-to-face meeting and an exchange of emails. The principles were reorganised under the four domains of the National Rural and Remote Nursing Generalist Framework and mapped against the National Safety and Quality Primary and Community Health Care Standards., Conclusion: The revised RAN MoC is designed to provide evidence based culturally informed care, standardise RAN consultation best practice and improve the health outcomes of their clients. With the increased turnover and number of nurses 'new' to remote, more innovative approaches to education and dissemination of the model is necessary., (© 2024 The Author(s). Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)
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- 2024
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16. Performance of clinical decision aids (CDA) for the care of young febrile infants: a multicentre prospective cohort study conducted in the UK and Ireland.
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Umana E, Mills C, Norman-Bruce H, Mitchell H, McFetridge L, Lynn F, McKeeman G, Foster S, Barrett MJ, Roland D, Lyttle MD, Watson C, and Waterfield T
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Background: Between 1% and 4% of febrile infants, aged from birth to 90 days of age, presenting to hospital will be diagnosed with an invasive bacterial infection (IBI). Traditional teaching has advocated a treat all approach but more recently a number of clinical decision aids (CDA) have been developed to classify febrile infants into lower and higher risk cohorts, with lower risk infants suitable for management without immediate parenteral antibiotics and lumbar puncture. The aim of this study was to apply these CDA to a UK and Irish cohort., Methods: This was a prospective multicentre cohort study of febrile infants presenting to 35 Paediatric Emergency Research in the UK and Ireland (PERUKI) sites between the 6th July 2022 and the 31st August 2023. All infants received standard care as per local policy. IBI was defined as growth of bacterial pathogen in blood or cerebrospinal fluid. The performance of the following CDAs were assessed, National Institute for Health and Care Excellence (NICE) guidelines NG143 (Fever under 5 years), British Society Antimicrobial Chemotherapy (BSAC), Aronson rule and American Academy of Pediatrics (AAP) CDA. A cost comparison of each CDA against a treat all approach was conducted. Trial registration: NCT05259683., Findings: 1821 were included in the final analysis. The median age was 46 days (IQR: 30-64 days), with 1108 (61%) being male. Of the 1821 infants, 67 (3.7%) had IBI. The AAP and BSAC CDAs were the most sensitive at 0.99 (95% CI 0.92-1.0) for both with specificities of 0.23 (95% CI 0.21-0.25) and 0.20 (95% CI 0.18-0.22) respectively. The NICE NG143 and Aronson CDA were the most specific CDAs with values of 0.27 (95% CI 0.25-0.30) and 0.30 (95% CI 0.28-0.32) respectively, but their sensitivity was lower. The AAP CDA performed equally well with either procalcitonin (PCT) or C-reactive protein (CRP) as the biomarker of choice. Of the 1821 infants, 77% were admitted, 14% were discharged and 9% were ambulated. All CDAs were cost saving for hospital services when compared to a treat all approach, with the lowest mean cost per patient estimated for Aronson (£1171; bootstrap 95% CI £1129-£1214) and NICE NG143 CDA (£1218; bootstrap 95% CI £1174-£1263)., Interpretation: The AAP and BSAC CDAs are highly sensitive at excluding IBI, with a cost saving to hospital services when compared to a treat all approach. The substitution of CRP for PCT made no difference to the performance of the AAP CDA in this cohort and was more costly., Funding: The Febrile Infant Diagnostic Assessment and Outcome (FIDO) study is funded by Royal College of Emergency Medicine Doctoral Fellowship (RCEM 02/03/2021). Procalcitonin analysis was supported by the Public Health Agency Northen Ireland Grant (HSC R&D-COM/5745/22). The funders played no part in the conception or design of this study., Competing Interests: No conflict of interest to declare., (Crown Copyright © 2024 Published by Elsevier Ltd.)
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- 2024
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17. Evolution of morphological changes in donor livers undergoing normothermic machine perfusion.
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Paterson AL, Gaurav R, Swift L, Webster R, Fear C, Butler AJ, and Watson CJE
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Aims: There is a shortage of livers for transplantation in the United Kingdom; despite this, more than a fifth of those retrieved are not transplanted. Normothermic machine perfusion (NMP) allows a functional assessment of marginal organs using biochemical parameters. This study describes the histological changes in livers undergoing NMP., Methods and Results: A total of 170 biopsies taken pre-NMP, after 4 h of NMP, end-NMP and at implantation from 50 livers undergoing NMP as part of standard local transplant practice were retrospectively reviewed. Thirty-eight per cent had large droplet macrovesicular steatosis pre-NMP, which was associated with reduced organ utilisation, P = 0.096, subsequent extracellular fat and a neutrophilic reaction; 32% had small droplet macrovesicular steatosis pre-NMP suggestive of acute cellular stress, the severity of which was unchanged in 64% during the perfusion period. Those showing at least moderate hepatocellular necrosis at end-NMP were less likely to be transplanted (55 versus 24%, P = 0.0505). Variation in the extent of hepatocyte necrosis was seen between biopsies, with 43% of transplanted cases showing less hepatocyte necrosis at implantation compared to end-NMP and 21% more severe necrosis. Patchy portal inflammation was present in 96% of pre-NMP biopsies, although identifiable duct injury was rare and portal thrombi were not identified. Sinusoidal dilation pre-NMP was more frequent in donation after circulatory death donors, typically persisted during NMP although had improved by implantation in most and had resolved in cases with an early post-transplant biopsy., Conclusions: Histological changes in NMP livers predominantly comprise donor-derived steatosis, stress-associated small droplet steatosis, retrieval- and procedure-associated sinusoidal dilation and ischaemic injury., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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18. The Impact of Intimate Partner Violence on Gay Men's Personal and Working Lives.
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Mayshak R, Harries T, Watson C, Curtis A, and Walker A
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Research into intimate partner violence (IPV) has focused on the experience of female victims resulting from dominant theoretical frameworks and societal biases casting females as victims and males as abusers. While emergent studies suggest that gay male victims experience a higher prevalence rate and more severe consequences from IPV than heterosexuals victims (male or female), few studies have explored the impact of IPV on gay male victims personal and working lives. We conducted a qualitative case study analysis using an Interpretive Phenomenological Analysis by interviewing four gay males with experience of IPV. Following a description of each case, a cross-case analysis identified the similarities and differences between the participants' lived experiences according to four main themes: 1) formal support, 2) informal support, 3) workplace support, and 4) workplace performance. We found that the influence of minority stress may amplify the challenges that some gay male victims face when conceptualizing their abuse and seeking support in their personal and working lives. Organizations should develop targeted and inclusive policies that support victims, with LGBTQI±competent Employee Assistance Program (EAP) providers, and gender-neutral language when referring to IPV.
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- 2024
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19. Community Organizations, Local Health Equity Action Teams, and a Learning Collaborative to Address COVID-19 Disparities in Urban and Rural Communities.
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Ellerbeck EF, Collie-Akers VL, Ablah E, Landry S, Honn A, Obermeier S, Ramirez M, Chen Y, Knight IR, Lumpkins CY, Ricketts M, Carter T, Wright U, Watson C, Kurz DL, McCrea-Robertson S, Finocchario-Kessler S, LeMaster J, Corriveau E, Crawford B, He J, and Greiner KA
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- Humans, Kansas, Urban Population, SARS-CoV-2, COVID-19 Testing, Health Status Disparities, Cooperative Behavior, COVID-19 epidemiology, COVID-19 prevention & control, Health Equity, Rural Population
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Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) Kansas worked with 10 Kansas counties from November 2020 through June 2022 to form local health equity action teams (LHEATs), develop COVID-19 testing strategies, foster communication about COVID-19, and share best practices through a learning collaborative. Participating counties documented 693 distinct COVID-19 testing and 178 communication activities. Although the intervention was not associated with changes in the proportion of positive COVID-19 tests, LHEATs in the learning collaborative implemented new testing strategies and responded to emerging COVID-19 challenges. ( Am J Public Health . 2024;114(11):1202-1206. https://doi.org/10.2105/AJPH.2024.307771).
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- 2024
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20. The impact of brain tissue oxygenation monitoring on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended in patients with moderate to severe traumatic brain injury: A systematic review.
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Shanahan R, Avsar P, Watson C, Moore Z, Patton D, McEvoy NL, Curley G, and O'Connor T
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- Humans, Brain metabolism, Intensive Care Units, Intracranial Pressure physiology, Length of Stay statistics & numerical data, Monitoring, Physiologic methods, Brain Injuries, Traumatic diagnosis, Brain Injuries, Traumatic mortality, Glasgow Outcome Scale
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Background: Traumatic brain injuries (TBIs) are one of the leading causes of death or long-term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long-term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP)., Aim: The aim of this review is to determine the impact of PbtO2 on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended (GOS/GOSE) in patients with moderate to severe TBI., Study Design: Systematic review with narrative and meta-analysis. All original research in which adult patients undergoing PbtO2 were compared with a control group of traditional ICP/cerebral perfusion pressure (CPP) monitoring. Both randomized controlled trials and observational studies were included in this review., Methods: Databases were searched in September 2022. The primary outcome of the review was the impact of PbtO2 monitoring on GOS/GOSE, while secondary outcomes were mortality and length of stay (LOS) in the intensive care unit (ICU)., Results: Seven studies with a combined number of 770 patients were included in the review. These patients were adults ≥16 years of age. Only two of the studies included found a statistically significant association between PbtO2 monitoring and improved long-term neurological outcomes in patients with TBI (p = .01, p < .01). A meta-analysis of the secondary outcomes identified an associated reduction of mortality in favour of the group treated with PbtO2 monitoring (p < .0001). Results from studies examining LOS in ICU have demonstrated an associated increase of LOS in ICU in patients treated with PbtO2-guided therapy., Conclusion: From the studies included in this review, only two found a statistically significant association between PbtO2 monitoring and long-term outcomes. It is unclear whether PbtO2 goal-directed therapy has a positive impact on the long-term neurological functions and mortality of patients suffering from TBI. A multicentre randomized controlled trial may provide further evidence, but not necessarily conclusive., Relevance to Clinical Practice: Further research is warranted to determine the efficacy of the introduction of this new monitoring system to guide local policy change., (© 2023 British Association of Critical Care Nurses.)
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- 2024
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21. Cataract surgery using two 3D visualization systems: Complication rates, surgical duration & comparison with traditional microscopes.
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Diakonis VF, Tsaousis KT, Watson C, Castellano K, and Weinstock RJ
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- Humans, Retrospective Studies, Male, Female, Aged, Postoperative Complications, Cataract Extraction, Intraoperative Complications, Middle Aged, Visual Acuity, Clinical Competence, Phacoemulsification, Aged, 80 and over, Laser Therapy methods, Lens Implantation, Intraocular, Imaging, Three-Dimensional, Microscopy, Operative Time
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Purpose: To compare the complication rates and surgical duration of cataract surgery using two 3D visualization systems and a traditional binocular microscope among experienced and inexperienced surgeons., Methods: This retrospective case series included 571 eyes that received cataract surgery using either heads up cataract surgery, via a 3D head mounted system ( N = 148-Group 1) or a 3D display screen ( N = 338 eyes-Group 2), or traditional binocular microscope ( N = 85 eyes-Group 3). The surgical records of consecutive patients who underwent cataract surgery by two groups of surgeons (experienced and inexperienced) were reviewed. Patients in all groups received either femtosecond laser assisted cataract surgery (FLACS) or traditional phacoemulsification. Complication rate, as well as duration of cataract surgery were evaluated between all three visualization approaches, between experienced and inexperienced surgeons., Results: There was no statistically significant difference in duration of surgery between all 3 visualization approaches for both experienced and inexperienced surgeons ( p < 0.05). Furthermore, the type of surgical technique (manual or FLACS) did not affect the surgical duration for both experienced and inexperienced surgeons ( p < 0.05). No intraoperative complications were demonstrated in the current cohort., Conclusions: The implementation of heads up-3D visualization either through a screen or a head mounted platform for cataract surgery seems to offer similar safety and efficiency as the traditional binocular microscope, and both experienced and inexperienced surgeons demonstrate the same outcomes in terms of safety and efficiency., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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22. The Oncology QCARD Initiative: Fostering efficient evaluation of initial real-world data proposals.
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Rivera DR, Eckert JC, Rodriguez-Watson C, Lerro CC, Bertagnolli MM, Hubbard RA, Kushi LH, Lund JL, Schrag D, Wang SV, Wood WA, Lee JJ, Okafor C, Ghauri K, Winckler SC, and Kluetz PG
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- Humans, Data Accuracy, Neoplasms, Research Design, Medical Oncology standards
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Purpose: The oncology quality, characterization, and assessment of real-world data (Oncology QCARD) Initiative was formed to develop a set of minimum study design and data elements needed to evaluate the fitness of the real-world data (RWD) source(s) proposed in an initial study concept as part of early interaction with scientific reviewers., Methods: A multidisciplinary executive committee (EC) was established to guide the Oncology QCARD Initiative. The EC conducted a landscape review of published literature, guidances, and guidelines to evaluate relevant dimensions of data quality measurement. Guided by the review and informed by expert feedback, the Oncology QCARD Initial Protocol Characterization (IPC) provides a summary of minimum elements needed to adequately describe an initial clinical study concept that involves RWD and is intended to support decision-making., Results: Fit-for-use data and fit-for-purpose design emerged as themes from the landscape analysis. Data that are fit-for-use are both relevant (sufficiently capturing exposure, outcomes, and covariates) and reliable (understanding data accrual and quality control and whether the data represent the underlying concepts they are intended to represent) to answer a specific research question. A fit-for-purpose design takes appropriate steps to ensure internal and external validity and allows for transparency in reporting. The QCARD-IPC focuses on high-level characteristics of RWD sources and study design domains including data temporality, population, medical product exposure, comparators, and covariates, endpoints, statistical analysis, and data quality assurance plans., Conclusions: Evaluation of studies including RWD requires understanding the data source, study design, and potential biases to preliminarily evaluate whether selected RWD are fit-for-use for the research question. The Oncology QCARD-IPC provides a structured, transparent approach to facilitate early review and enhanced communication between study sponsors and scientific reviewers of initial study proposals including RWD., (© 2024 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
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- 2024
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23. Prevention of respiratory syncytial virus disease by immunisation.
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Benzaken TR, Watson C, and Drysdale SB
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Competing Interests: Competing interests: SBD has previously received honoraria from Sanofi for taking part in RSV advisory boards and has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD and Sanofi with fees paid to his institution. SBD is a member of the UK Department of Health and Social Care (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and Medicines and Healthcare products Regulatory Agency (MHRA) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA or PMEAG.
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- 2024
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24. New programme to prevent bronchiolitis in infants.
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Pollard AJ, Ramsay ME, and Watson C
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Competing Interests: Competing interests: AJP is chair of JCVI. MER and CW are employees of UKHSA; UKHSA has provided vaccine manufacturers with postmarketing surveillance reports on meningococcal, Haemophilus influenzae and pneumococcal infections, which the companies are required to submit to the UK Licensing Authority in compliance with their risk management strategy. A cost recovery charge is made for these reports.
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- 2024
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25. The Resurgence of Mpox in Africa.
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Rivers C, Watson C, and Phelan AL
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- Female, Humans, Male, Africa epidemiology, Monkeypox virus pathogenicity, Global Health statistics & numerical data, Smallpox Vaccine administration & dosage, Smallpox Vaccine supply & distribution, Mpox, Monkeypox epidemiology, Mpox, Monkeypox transmission, Mpox, Monkeypox virology, Disease Outbreaks prevention & control, Disease Outbreaks statistics & numerical data
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- 2024
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26. Role of diagnostic tests for sepsis in children: a review.
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Rodgers O, Mills C, Watson C, and Waterfield T
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- Humans, Child, Procalcitonin blood, C-Reactive Protein analysis, Sepsis diagnosis, Sepsis blood, Biomarkers blood
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Paediatric sepsis has a significant global impact and highly heterogeneous clinical presentation. The clinical pathway encompasses recognition, escalation and de-escalation. In each aspect, diagnostics have a fundamental influence over outcomes in children. Biomarkers can aid in creating a larger low-risk group of children from those in the clinical grey area who would otherwise receive antibiotics 'just in case'. Current biomarkers include C reactive protein and procalcitonin, which are limited in their clinical use to guide appropriate and rapid treatment. Biomarker discovery has focused on single biomarkers, which, so far, have not outperformed current biomarkers, as they fail to recognise the complexity of sepsis. The identification of multiple host biomarkers that may form a panel in a clinical test has the potential to recognise the complexity of sepsis and provide improved diagnostic performance. In this review, we discuss novel biomarkers and novel ways of using existing biomarkers in the assessment and management of sepsis along with the significant challenges in biomarker discovery at present. Validation of biomarkers is made less meaningful due to methodological heterogeneity, including variations in sepsis diagnosis, biomarker cut-off values and patient populations. Therefore, the utilisation of platform studies is necessary to improve the efficiency of biomarkers in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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27. Clonal dynamics and somatic evolution of haematopoiesis in mouse.
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Kapadia CD, Williams N, Dawson KJ, Watson C, Yousefzadeh MJ, Le D, Nyamondo K, Cagan A, Waldvogel S, De La Fuente J, Leongamornlert D, Mitchell E, Florez MA, Aguilar R, Martell A, Guzman A, Harrison D, Niedernhofer LJ, King KY, Campbell PJ, Blundell J, Goodell MA, and Nangalia J
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Haematopoietic stem cells maintain blood production throughout life. While extensively characterised using the laboratory mouse, little is known about how the population is sustained and evolves with age. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1845 single cell-derived colonies, and used phylogenetic analysis to infer the ontogeny and population dynamics of the stem cell pool. Mouse stem cells and progenitors accrue ~45 somatic mutations per year, a rate only about 2-fold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns reveal that stem and multipotent progenitor cell pools are both established during embryogenesis, after which they independently self-renew in parallel over life. The stem cell pool grows steadily over the mouse lifespan to approximately 70,000 cells, self-renewing about every six weeks. Aged mice did not display the profound loss of stem cell clonal diversity characteristic of human haematopoietic ageing. However, targeted sequencing revealed small, expanded clones in the context of murine ageing, which were larger and more numerous following haematological perturbations and exhibited a selection landscape similar to humans. Our data illustrate both conserved features of population dynamics of blood and distinct patterns of age-associated somatic evolution in the short-lived mouse.
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- 2024
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28. A comparative study of influenza surveillance systems and administrative data in England during the 2022-2023 season.
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Mellor J, Christie R, Guilder J, Paton RS, Elgohari S, Watson C, Deeny SR, and Ward T
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Accurate and representative surveillance is essential for understanding the impact of influenza on healthcare systems. During the 2022-2023 influenza season, the Northern Hemisphere experienced its most significant epidemic wave since the onset of the COVID-19 pandemic in 2020. Concurrently, new surveillance systems, developed in response to the pandemic, became available within health services. In this study, we analysed per capita admission rates from National Health Service hospital Trusts across four surveillance systems in England during the winter of 2022-2023. We examined differences in reporting timeliness, data completeness, and regional coverage, modelling key epidemic metrics including the maximum admission rates, cumulative seasonal admissions, and growth rates by fitting generalised additive models at national and regional levels. From modelling the admission rates per capita, we find that different surveillance systems yield varying estimates of key epidemiological metrics, both spatially and temporally. While national data from these systems generally align on the maximum admission rate and growth trends, discrepancies emerge at the subnational level, particularly in the cumulative admission rate estimates, with notable issues observed in London and the East of England. The rapid growth and decay phases of the epidemic contributed to higher uncertainty in these estimates, especially in regions with variable data quality. The study highlights that the choice of surveillance system can significantly influence the interpretation of influenza trends, especially at the subnational level, where regional disparities may mask true epidemic dynamics. Comparing multiple data sources enhances our understanding of the impact of seasonal influenza epidemics and highlights the limitations of relying on a single system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mellor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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29. Characteristics of Global Rapid Response Team Deployers and Deployment, United States, 2019-2022.
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Lammie SL, Habib M, Bugli D, Worrell MC, Talley L, Neatherlin JC, Dubray C, and Watson C
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The Centers for Disease Control and Prevention's (CDC's) Global Rapid Response Team (GRRT) was created in 2015 to efficiently deploy multidisciplinary CDC experts outside the United States for public health emergencies. The COVID-19 pandemic dramatically increased the need for domestic public health responders. This study aimed to follow up on previously published data to describe the GRRT surge staffing model during the height of the COVID-19 response. We conducted descriptive analyses to assess GRRT deployment characteristics during April 1, 2019-March 31, 2022, and characteristics of responders rostered in 2021 and 2022. We analyzed data on response events, remote versus in-person work, and international versus domestic deployment location. We also examined the number of responders on call per month, language proficiency, and technical skills. During the study period, 1725 deployments were registered, accounting for 82 058 person-days deployed. Of all person-days deployed during the study period, 82% were related to COVID-19. Eighty-seven percent of all person-days deployed were domestic. Virtual deployments that were not in person accounted for 51% of deployments registered, yet these resulted in 67% of person-days deployed. The median deployment duration was 31 days. We found a median of 79 surge responders on call each month. Among 608 responders rostered in 2021 and 2022, 35% self-reported proficiency in a second language. Epidemiology was the most common technical skill (38%). GRRT transitioned to primarily remote, domestic deployments to support the COVID-19 pandemic response. The GRRT model demonstrates how response structure shifted to address the global health threat of a pandemic., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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30. Emulations of Oncology Trials Using Real-World Data: A Systematic Literature Review.
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Rider JR, Wasserman A, Slipski L, Carrigan G, Harvey R, Jiao X, McRoy L, Pace ND, Becnel L, Bruno A, Eckert JC, Hodgkins P, Jain P, Merola D, Ovbiosa OE, Natanzon Y, Pinheiro S, Quinn J, Rodriguez-Watson C, and Campbell U
- Abstract
By evaluating published emulations of oncology RCTs studies in which both the active and comparator groups are sourced from RWD and target trial results are available for benchmarking, this systematic review aims to gain insight into factors related to emulation performance. Thirteen oncology emulation studies using various types of RWD were identified through an online database search of PubMed through 2022. Based on the ROBINS-I tool, most studies (N=8) had a serious risk of overall bias driven by risk of bias from confounding. Approximately half of the studies (N=6) fully proxied the RCT entry criteria. Of 11 RWD studies that provided sufficient detail to quantify emulation performance, the emulation HR estimate fell within the 95% CI of the trial estimate in 9 of the studies. There were no clear trends between risk of bias or degree to which the entry criteria were proxied and emulation performance. Findings may have been influenced by publication bias and researcher degrees of freedom, as only one emulation study pre-registered its protocol. Tools for comprehensively characterizing factors that affect emulation performance, including the real-world clinical context as it relates to the RCT research question, are needed to evaluate the feasibility of a RCT emulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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31. The gut microbiome and chronic pain.
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Watson C
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- Animals, Humans, Mice, Endometriosis complications, Endometriosis microbiology, Female, Chronic Pain etiology, Chronic Pain microbiology, Gastrointestinal Microbiome physiology
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- 2024
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32. The impact of burnout on paediatric nurses' attitudes about patient safety in the acute hospital setting: A systematic review.
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Flynn C, Watson C, Patton D, and O'Connor T
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- Humans, Female, Male, Adult, Burnout, Professional psychology, Burnout, Professional prevention & control, Patient Safety, Attitude of Health Personnel, Nurses, Pediatric psychology, Pediatric Nursing, Nursing Staff, Hospital psychology, Job Satisfaction
- Abstract
Background: Patient safety is the cornerstone of quality healthcare. Nurses have a duty to provide safe care, particularly to vulnerable populations such as paediatric patients. Demands on staff and resources are rising and burnout is becoming an increasingly prevalent occupational hazard in paediatric healthcare today. Occupational stress is a barrier to maintaining a positive patient safety culture., Purpose: This paper seeks to explore the impact of burnout on paediatric nurses' attitudes about patient safety., Methods: A systematic review approach was used. Embase, Cochrane Library, Medline, CINAHL, and PsycINFO were the databases searched. All quantitative, primary, empirical studies, published in English, which investigated associations between burnout and attitudes to patient safety in the paediatric nursing workforce were included., Results: Four studies were eligible for inclusion. These studies examined a total of 2769 paediatric nurses. Pooled data revealed overall moderate to high levels of burnout. All studies exposed a negative association between emotional exhaustion and safety attitude scoring (r = -0.301- -0.481). Three studies demonstrated a negative association to job satisfaction (r = -0.424- -0.474). The potential link between burnout and an increased frequency of adverse events was also highlighted., Conclusions: Burnout may negatively impact paediatric nurses' attitudes to patient safety in the acute hospital setting. Targeted interventions to tackle burnout are urgently required to protect both paediatric nurses and patients., Implications: Managers and policy makers must promote nurse well-being to safeguard staff and patients. Educational interventions are required to target burnout and promote patient safety. Further research is required to investigate the long-term impact of burnout., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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33. EU's Medical Device Expert Panels: Analysis of Membership and Published Clinical Evaluation Consultation Procedure (CECP) Results.
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Watson C and Richmond FJ
- Subjects
- Humans, Equipment and Supplies, Device Approval legislation & jurisprudence, Advisory Committees, European Union
- Abstract
Background: The new EU Medical Device Regulation (MDR) places greater importance on the role of clinical evidence to establish safety and performance. Article 54 of the MDR calls for expert committees to independently review the scientific, technical, and clinical evidence supporting the market authorization of certain novel devices independently from the established process of Notified Body reviews. These experts provide a review and opinion that ultimately is taken into consideration alongside the information reviewed by the Notified Body during the review process. Four expert committees (General and Plastic Surgery and Dentistry; Orthopaedics, Traumatology, Rehabilitation, Rheumatology; Circulatory System; and Neurology) have published at least one Scientific Opinion (SO) under the Clinical Evaluation Consultation Procedure (CECP) in 2021-2022., Methods: The four expert committees with published CECP opinions were reviewed to assess the academic backgrounds and professional expertise of each member with respect to clinical, technical, and biological domains on a 0-2 scale for each domain. A content review was conducted on the 10 CECP opinions published by these committees to assess their consistency with the goals and outcome expectations set by the MDR. The extent of content related to each of the clinical, technical, and biological domains was also assessed on a 0-2 scale., Results: All committees were composed primarily by members with strong clinical expertise, but only a few had strong technical and biological expertise. Across committees, the average scores of members related to academic background and professional expertise both ranged from 1.64 to 2.00 in the clinical domain, but only 0-0.15 and 0.15-0.69, respectively, in the biological domain, and 0.12-0.55 and 0.23-0.73, respectively, in the technical domain. A content review for the 10 SOs showed that all opinions focused exclusively or primarily on the clinical evidence. Three contained a modest amount of additional text directed at technical/engineering issues and five at biological issues., Conclusion: Expert committees are composed predominantly of expert clinical reviewers but have many fewer members with significant technical or biological expertise. This may limit the ability of the committees to evaluate the significant technical and biological risks that are often best understood by preclinical testing. Broadening the expertise across the committees may improve the depth of their benefit/risk critiques., (© 2024. The Author(s).)
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- 2024
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34. Informing the management of the post-COVID condition: insights from the Western Australian experience comparing those who tested positive and negative to early COVID-19 strains.
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Grove K, Cavalheri V, Chih H, Natarajan V, Harrold M, Mohd S, Hurn E, Van der Lee L, Maiorana A, Tearne J, Watson C, Pearce J, Jacques A, White A, Vicary C, Roffman C, Synnott EL, Suttie I, Lin I, Larsson J, Naylor L, Woodhouse L, Elliott M, Gittings P, Winship P, Timms R, Wulff S, Hebden-Todd T, and Edgar DW
- Abstract
ObjectiveThis study aimed to compare the relative physical recovery and symptoms after SARS-CoV-2 infection between groups confirmed positive or negative to early strains of COVID-19.MethodsA prospective, longitudinal cohort study compared outcomes of metropolitan adults polymerase chain reaction-tested for COVID-19 between March and November 2020 in Western Australia. Control matching was attempted: inpatients (gender, age) and ambulatory clinic (gender, age, asthma, chronic pulmonary disease). One-year follow-up involved three repeated measures: physical function (grip strength and 1-min sit-to-stand) and patient-reported outcomes (Fatigue Severity Scale, modified Medical Research Council dyspnoea scale and Euroqol-5D-5L).ResultsThree hundred and forty-four participants were recruited (154 COVID+, age 54±18years, 75 females [49%]); 190 COVID-, age 52±16years, 67 females [35%]) prior to national vaccination roll-out. No between-group differences in physical function measures were evident at any time point. Fatigue (OR 6.62, 95% CI 2.74-15.97) and dyspnoea (OR 2.21, 95% CI 1.14-4.30) were higher in the COVID+ group at second assessment (T2). On Euroqol-5D-5L, no between-group differences were evident in the physical function domains of self-care, mobility or usual activities at any time point. However, COVID+ participants were less likely to report an absence of anxiety or depression symptoms at T2 (OR 0.41, 95% CI 0.19-0.89).ConclusionsNeither statistical nor clinically meaningful differences in physical function were evident between COVID+ and COVID- participants to 12-months after acute illness. Symptoms of fatigue, dyspnoea, anxiety or depression were more prevalent in the COVID+ group til ~8months after illness with between-group differences no longer evident at 1 year.
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- 2024
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35. Assessing Assembly Errors in Immunoglobulin Loci: A Comprehensive Evaluation of Long-read Genome Assemblies Across Vertebrates.
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Zhu Y, Watson C, Safonova Y, Pennell M, and Bankevich A
- Abstract
Long-read sequencing technologies have revolutionized genome assembly producing near-complete chromosome assemblies for numerous organisms, which are invaluable to research in many fields. However, regions with complex repetitive structure continue to represent a challenge for genome assembly algorithms, particularly in areas with high heterozygosity. Robust and comprehensive solutions for the assessment of assembly accuracy and completeness in these regions do not exist. In this study we focus on the assembly of biomedically important antibody-encoding immunoglobulin (IG) loci, which are characterized by complex duplications and repeat structures. High-quality full-length assemblies for these loci are critical for resolving haplotype-level annotations of IG genes, without which, functional and evolutionary studies of antibody immunity across vertebrates are not tractable. To address these challenges, we developed a pipeline, "CloseRead", that generates multiple assembly verification metrics for analysis and visualization. These metrics expand upon those of existing quality assessment tools and specifically target complex and highly heterozygous regions. Using CloseRead, we systematically assessed the accuracy and completeness of IG loci in publicly available assemblies of 74 vertebrate species, identifying problematic regions. We also demonstrated that inspecting assembly graphs for problematic regions can both identify the root cause of assembly errors and illuminate solutions for improving erroneous assemblies. For a subset of species, we were able to correct assembly errors through targeted reassembly. Together, our analysis demonstrated the utility of assembly assessment in improving the completeness and accuracy of IG loci across species., Competing Interests: Competing interests The authors report no competing interests.
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- 2024
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36. The Ruminant Telomere-to-Telomere (RT2T) Consortium.
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Kalbfleisch TS, McKay SD, Murdoch BM, Adelson DL, Almansa-Villa D, Becker G, Beckett LM, Benítez-Galeano MJ, Biase F, Casey T, Chuong E, Clark E, Clarke S, Cockett N, Couldrey C, Davis BW, Elsik CG, Faraut T, Gao Y, Genet C, Grady P, Green J, Green R, Guan D, Hagen D, Hartley GA, Heaton M, Hoyt SJ, Huang W, Jarvis E, Kalleberg J, Khatib H, Koepfi KP, Koltes J, Koren S, Kuehn C, Leeb T, Leonard A, Liu GE, Low WY, McConnell H, McRae K, Miga K, Mousel M, Neibergs H, Olagunju T, Pennell M, Petry B, Pewsner M, Phillippy AM, Pickett BD, Pineda P, Potapova T, Rachagani S, Rhie A, Rijnkels M, Robic A, Rodriguez Osorio N, Safonova Y, Schettini G, Schnabel RD, Sirpu Natesh N, Stegemiller M, Storer J, Stothard P, Stull C, Tosser-Klopp G, Traglia GM, Tuggle CK, Van Tassell CP, Watson C, Weikard R, Wimmers K, Xie S, Yang L, Smith TPL, O'Neill RJ, and Rosen BD
- Subjects
- Animals, Evolution, Molecular, Genome genetics, Selection, Genetic, Phylogeny, Diploidy, Telomere genetics, Ruminants genetics
- Abstract
Telomere-to-telomere (T2T) assemblies reveal new insights into the structure and function of the previously 'invisible' parts of the genome and allow comparative analyses of complete genomes across entire clades. We present here an open collaborative effort, termed the 'Ruminant T2T Consortium' (RT2T), that aims to generate complete diploid assemblies for numerous species of the Artiodactyla suborder Ruminantia to examine chromosomal evolution in the context of natural selection and domestication of species used as livestock., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2024
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37. Validation of an acute respiratory infection phenotyping algorithm to support robust computerised medical record-based respiratory sentinel surveillance, England, 2023.
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Elson WH, Jamie G, Wimalaratna R, Forbes A, Leston M, Okusi C, Byford R, Agrawal U, Todkill D, Elliot AJ, Watson C, Zambon M, Morbey R, Lopez Bernal J, Hobbs FR, and de Lusignan S
- Subjects
- Humans, England epidemiology, Acute Disease, Medical Records Systems, Computerized, Influenza, Human diagnosis, Influenza, Human epidemiology, Male, Female, Primary Health Care, Electronic Health Records, Sentinel Surveillance, Algorithms, Respiratory Tract Infections diagnosis, Respiratory Tract Infections epidemiology, Phenotype
- Abstract
IntroductionRespiratory sentinel surveillance systems leveraging computerised medical records (CMR) use phenotyping algorithms to identify cases of interest, such as acute respiratory infection (ARI). The Oxford-Royal College of General Practitioners Research and Surveillance Centre (RSC) is the English primary care-based sentinel surveillance network.AimThis study describes and validates the RSC's new ARI phenotyping algorithm.MethodsWe developed the phenotyping algorithm using a framework aligned with international interoperability standards. We validated our algorithm by comparing ARI events identified during the 2022/23 influenza season in England through use of both old and new algorithms. We compared clinical codes commonly used for recording ARI.ResultsThe new algorithm identified an additional 860,039 cases and excluded 52,258, resulting in a net increase of 807,781 cases (33.84%) of ARI compared to the old algorithm, with totals of 3,194,224 cases versus 2,386,443 cases. Of the 860,039 newly identified cases, the majority (63.7%) were due to identification of symptom codes suggestive of an ARI diagnosis not detected by the old algorithm. The 52,258 cases incorrectly identified by the old algorithm were due to inadvertent identification of chronic, recurrent, non-infectious and other non-ARI disease.ConclusionWe developed a new ARI phenotyping algorithm that more accurately identifies cases of ARI from the CMR. This will benefit public health by providing more accurate surveillance reports to public health authorities. This new algorithm can serve as a blueprint for other CMR-based surveillance systems wishing to develop similar phenotyping algorithms.
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- 2024
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38. Imputing Single-Cell Protein Abundance in Multiplex Tissue Imaging.
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Kirchgaessner R, Watson C, Creason A, Keutler K, and Goecks J
- Abstract
Multiplex tissue imaging are a collection of increasingly popular single-cell spatial proteomics and transcriptomics assays for characterizing biological tissues both compositionally and spatially. However, several technical issues limit the utility of multiplex tissue imaging, including the limited number of molecules (proteins and RNAs) that can be assayed, tissue loss, and protein probe failure. In this work, we demonstrate how machine learning methods can address these limitations by imputing protein abundance at the single-cell level using multiplex tissue imaging datasets from a breast cancer cohort. We first compared machine learning methods' strengths and weaknesses for imputing single-cell protein abundance. Machine learning methods used in this work include regularized linear regression, gradient-boosted regression trees, and deep learning autoencoders. We also incorporated cellular spatial information to improve imputation performance. Using machine learning, single-cell protein expression can be imputed with mean absolute error ranging between 0.05-0.3 on a [0,1] scale. Finally, we used imputed data to predict whether single cells were more likely to come from pre-treatment or post-treatment biopsies. Our results demonstrate (1) the feasibility of imputing single-cell abundance levels for many proteins using machine learning; (2) how including cellular spatial information can substantially enhance imputation results; and (3) the use of single-cell protein abundance levels in a use case to demonstrate biological relevance.
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- 2024
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39. Clinical application of paediatric serum troponin T testing.
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McGinn C, Watson C, McKeeman G, Mauger B, Morrison L, and Casey FA
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- Humans, Child, Troponin T blood, Biomarkers blood
- Abstract
Competing Interests: Competing interests: None declared.
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- 2024
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40. Respiratory syncytial virus-associated pneumonia in primary care in Malawi.
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Davy K, Koskinas E, Watson C, Ledwidge M, Mbakaya B, Chisale M, and Gallagher J
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- Humans, Malawi epidemiology, Male, Female, Infant, Prospective Studies, Child, Preschool, Prevalence, Risk Factors, Respiratory Syncytial Virus, Human isolation & purification, Infant, Newborn, Pneumonia epidemiology, Pneumonia virology, Pneumonia diagnosis, Pneumonia, Viral epidemiology, Pneumonia, Viral diagnosis, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections diagnosis, Primary Health Care, Community-Acquired Infections epidemiology, Community-Acquired Infections virology
- Abstract
Objective: To identify the prevalence of respiratory syncytial virus (RSV) in a cohort of children under 5 years of age with World Health Organization (WHO)-defined pneumonia and the factors associated with developing severe RSV-associated community-acquired pneumonia (CAP) in primary care in a single centre in Northern Malawi., Methods: The BIOmarkers TO diagnose PnEumonia (BIOTOPE) study was a prospective cohort study conducted from March to June 2016 that took place in a primary care centre in Northern Malawi. Data from this study was used to identify the characteristics of children under 5 years of age who presented with RSV and WHO-defined CAP. Means, standard deviations, medians and ranges were calculated for continuous variables. A univariate logistic regression was performed to examine the potential predictor variables., Results: Four hundred and ninety-four infants presented with CAP and were eligible for inclusion in the study; RSV infection was detected in 205 (41.6%) of the infants. Eight factors were associated with increased risk for RSV CAP in the univariate model: age, born at term, presenting for care in June, crowded living environment, not being exclusively breastfed, not having received zinc or vitamin A supplementation in the last six months. Infants with RSV were more likely to have an oxygen saturation ≤92% compared to infants with other causes of pneumonia and more likely to have severe pneumonia as defined by the WHO., Conclusion: This study supports that RSV-associated CAP is linked to modifiable and non-modifiable risk factors; further research is indicated to determine which interventions would be most impactful. Developing and implementing an infant or maternal vaccine could be a cost-effective way to prevent RSV-associated CAP and mortality in developing nations. More research is needed to understand seasonal patterns of CAP and research over extended periods can offer valuable insights on host, environmental and pathogen-specific factors that contribute to RSV-associated CAP., (© The Author(s) [2024]. Published by Oxford University Press.)
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- 2024
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41. The Evolution of Ultraconserved Elements in Vertebrates.
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Cummins M, Watson C, Edwards RJ, and Mattick JS
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- Animals, Humans, Genome, Phylogeny, Evolution, Molecular, Conserved Sequence, Vertebrates genetics
- Abstract
Ultraconserved elements were discovered two decades ago, arbitrarily defined as sequences that are identical over a length ≥ 200 bp in the human, mouse, and rat genomes. The definition was subsequently extended to sequences ≥ 100 bp identical in at least three of five mammalian genomes (including dog and cow), and shown to have undergone rapid expansion from ancestors in fish and strong negative selection in birds and mammals. Since then, many more genomes have become available, allowing better definition and more thorough examination of ultraconserved element distribution and evolutionary history. We developed a fast and flexible analytical pipeline for identifying ultraconserved elements in multiple genomes, dedUCE, which allows manipulation of minimum length, sequence identity, and number of species with a detectable ultraconserved element according to specified parameters. We suggest an updated definition of ultraconserved elements as sequences ≥ 100 bp and ≥97% sequence identity in ≥50% of placental mammal orders (12,813 ultraconserved elements). By mapping ultraconserved elements to ∼200 species, we find that placental ultraconserved elements appeared early in vertebrate evolution, well before land colonization, suggesting that the evolutionary pressures driving ultraconserved element selection were present in aquatic environments in the Cambrian-Devonian periods. Most (>90%) ultraconserved elements likely appeared after the divergence of gnathostomes from jawless predecessors, were largely established in sequence identity by early Sarcopterygii evolution-before the divergence of lobe-finned fishes from tetrapods-and became near fixed in the amniotes. Ultraconserved elements are mainly located in the introns of protein-coding and noncoding genes involved in neurological and skeletomuscular development, enriched in regulatory elements, and dynamically expressed throughout embryonic development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
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- 2024
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42. Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors.
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Steeghs N, Gomez-Roca C, Rohrberg KS, Mau-Sørensen M, Robbrecht D, Tabernero J, Ahmed S, Rodríguez-Ruiz ME, Ardeshir C, Schmid D, Sleiman N, Watson C, Piper-Lepoutre H, Dejardin D, Evers S, Boetsch C, Charo J, Teichgräber V, and Melero I
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Interleukin-2 administration & dosage, Interleukin-2 adverse effects, Interleukin-2 pharmacokinetics, Interleukin-2 genetics, Neoplasm Metastasis, Recombinant Fusion Proteins pharmacokinetics, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins adverse effects, Recombinant Fusion Proteins therapeutic use, Treatment Outcome, Endopeptidases administration & dosage, Membrane Proteins, Neoplasms drug therapy, Neoplasms pathology, Neoplasms genetics, Maximum Tolerated Dose
- Abstract
Purpose: Simlukafusp alfa [fibroblast activation protein α-targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an IL2 variant moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast activation protein α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors., Patients and Methods: Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intraparticipant uptitration regimens (15/20, 20/25, 20/20/35, and 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities, maximum tolerated dose, recommended expansion dose, and pharmacokinetics., Results: Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (uptitration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). The uptitration regimen 15/20 mg was determined as the maximum tolerated dose and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses [NK cells, 13-fold; CD4+ T cells (including regulatory T cells), 2-fold; CD8+ T cells, 3.5-fold] but without any percentage change in regulatory T cells. Clinical activity was observed from 5 mg [objective response rate, 5.1% (n = 3); disease control rate, 27.1% (n = 16)]. Responses were durable [n = 3, 2.8 (censored), 6.3, and 43.4 months]., Conclusions: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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43. The effects of racial and socioeconomic disparities on time to diagnosis and treatment of pediatric functional seizures in the United States.
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Watson C, Crichlow Q, Valaiyapathi B, Szaflarski JP, and Fobian AD
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- Adolescent, Child, Female, Humans, Male, Educational Status, Healthcare Disparities ethnology, Healthcare Disparities statistics & numerical data, Income statistics & numerical data, Social Class, Socioeconomic Disparities in Health, Socioeconomic Factors, United States, Race Factors, Seizures diagnosis, Seizures therapy, Seizures ethnology, Time-to-Treatment statistics & numerical data
- Abstract
Purpose: The present study sought to assess the effects of racial and socioeconomic status in the United States on time to treatment and diagnosis of pediatric functional seizures (FS)., Methods: Eighty adolescents and their parent/guardian completed a demographics questionnaire and reported date of FS onset, diagnosis, and treatment. Paired samples t-tests compared time between FS onset and diagnosis, onset and treatment, and diagnosis and treatment based on race (White vs racial minority), annual household income (≤$79,999 vs ≥$80,000), maternal and paternal education (≤Associate's Degree vs Bachelor's Degree), and combined parental education (≤Post-graduate training vs Graduate degree)., Results: Adolescents with lower annual household income began treatment >6 months later than adolescents with greater annual household income (p = 0.049). Adolescents with lower maternal and paternal education (≤Associate's Degree vs Bachelor's Degree) began treatment >4 and ∼8.5 months later than adolescents with greater maternal and paternal education (p = 0.04; p = 0.03), respectively. Adolescents with lower maternal education also received a diagnosis >5 months later (p = 0.03). Adolescents without a mother or father with a graduate degree received a diagnosis and began treatment∼3 and >11 months later (p = 0.03; p = 0.01) than adolescents whose mother or father received a graduate degree, respectively. No racial differences were found., Conclusions: Adolescents with lower annual household income and/or parental education experienced increased duration between FS onset and treatment and diagnosis. Research is needed to clarify the mechanisms underlying this relationship, and action is needed to reduce these disparities given FS duration is associated with poorer prognosis and greater effects on the brain., Competing Interests: Declaration of competing interest Aaron Fobian reports grants from NIMH 1R61MH127155, payment from the Child Neurology Society for conference presentation, and Editorial board membership at Sleep Health and SLEEP Advances., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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44. Human placental lactogen (human chorionic somatomammotropin) and oxytocin during pregnancy: Individual patterns and associations with maternal-fetal attachment, anxiety, and depression.
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Coté JJ, Coté RD, Dilsaver DB, Stessman HAF, Watson C, Handelzalts J, Doehrman P, Walters RW, and Badura-Brack AS
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- Humans, Female, Pregnancy, Adult, Young Adult, Object Attachment, Oxytocin blood, Placental Lactogen blood, Anxiety blood, Anxiety psychology, Depression blood, Depression psychology, Maternal-Fetal Relations psychology, Maternal-Fetal Relations physiology
- Abstract
Previous studies support links among maternal-fetal attachment, psychological symptoms, and hormones during pregnancy and the post-partum period. Other studies connect maternal feelings and behaviors to oxytocin and suggest that an increase in oxytocin during pregnancy may prime maternal-fetal attachment. To date, researchers have not examined a possible association between maternal-fetal attachment with human placental lactogen although animal models are suggestive. In the current study, we sought to describe oxytocin and human placental lactogen levels as related to psychological constructs across pregnancy. Seventy women participated in the study. At each of three time-points (early, mid, and late pregnancy), the women had their blood drawn to assess oxytocin and human placental lactogen levels, and they completed psychological assessments measuring maternal-fetal attachment, anxiety, and depression. Our results indicate that oxytocin levels were statistically similar across pregnancy, but that human placental lactogen significantly increased across pregnancy. Results did not indicate significant associations of within-person (comparing individuals to themselves) oxytocin or human placental lactogen levels with maternal-fetal attachment. Additionally, results did not show between-person (comparing individuals to other individuals) oxytocin or human placental lactogen levels with maternal-fetal attachment. Oxytocin levels were not associated with anxiety; rather the stage of pregnancy moderated the effect of the within-person OT level on depression. Notably, increasing levels of human placental lactogen were significantly associated with increasing levels of both anxiety and depression in between subject analyses. The current study is important because it describes typical hormonal and maternal fetal attachment levels during each stage of pregnancy, and because it suggests an association between human placental lactogen and psychological symptoms during pregnancy. Future research should further elucidate these relationships., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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45. The Potential of Real-Time Behavior and Well-Being Assessments to Improve Medical Student Wellness.
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Milne A, Novelli A, Watson C, Yousef H, Holterman LA, Rosen L, Bai Y, Curl A, Gengel B, Hudziak JJ, and Copeland WE
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- Humans, Female, Male, Surveys and Questionnaires, Health Promotion methods, Health Behavior, Smartphone, Vermont, Adult, Students, Medical psychology, Mobile Applications
- Abstract
Problem: Medical students experience psychological distress more frequently than age-matched peers. Tracking medical student well-being has typically been limited to once- or twice-per-year questionnaires. Ongoing, real-time assessment of student behavior and well-being could facilitate individualized, timely interventions., Approach: Faculty at the University of Vermont, in conjunction with the Larner College of Medicine Office of Medical Education, developed a novel smartphone app in 2021 called WE MD to track and support medical student wellness. The app included the following features: (1) nightly surveys assessing wellness-related behaviors (e.g., social interaction, sleep, exercise) and outcomes (i.e., mood, focus, stress, overall well-being); (2) health reports that enabled users to graph various combinations of their own behaviors and outcomes, allowing them to visualize trends and understand possible correlations between behaviors and outcomes; (3) a resource library with articles and educational videos related to specific wellness behaviors or outcomes; and (4) research-based "insights" or brief tips intended to promote healthy habits. Participants also received virtual "coins" for interacting with the app that could be exchanged for various items in an online store., Outcomes: The WE MD program enrolled a substantial portion of the medical school population (43%); most of the students used the app on a regular basis. Students found the app to be acceptable and appreciated many features and also provided feedback on how to improve the app. Information from the nightly survey data converged with established measures but also identified variability over time in wellness behaviors and outcomes., Next Steps: Data from the WE MD program suggest that app-based daily tracking of wellness behaviors and outcomes is a feasible, promising approach to promote student wellness and identify real-time patterns and risk periods for medical students. The app will be revised based on student feedback and adapted for use by students, residents, and faculty., (Copyright © 2024 the Association of American Medical Colleges.)
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- 2024
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46. Biochemical and functional characterization of the p.A165T missense variant of mitochondrial amidoxime-reducing component 1.
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Hou W, Watson C, Cecconie T, Bolaki MN, Brady JJ, Lu Q, Gatto GJ Jr, and Day TA
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- Humans, Hep G2 Cells, Ubiquitination, Protein Stability, Proteasome Endopeptidase Complex metabolism, Proteasome Endopeptidase Complex genetics, Proteolysis, Oxidoreductases, Mutation, Missense, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism
- Abstract
Recent genome-wide association studies have identified a missense variant p.A165T in mitochondrial amidoxime-reducing component 1 (mARC1) that is strongly associated with protection from all-cause cirrhosis and improved prognosis in nonalcoholic steatohepatitis. The precise mechanism of this protective effect is unknown. Substitution of alanine 165 with threonine is predicted to affect mARC1 protein stability and to have deleterious effects on its function. To investigate the mechanism, we have generated a knock-in mutant mARC1 A165T and a catalytically dead mutant C273A (as a control) in human hepatoma HepG2 cells, enabling characterization of protein subcellular distribution, stability, and biochemical functions of the mARC1 mutant protein expressed from its endogenous locus. Compared to WT mARC1, we found that the A165T mutant exhibits significant mislocalization outside of its traditional location anchored in the mitochondrial outer membrane and reduces protein stability, resulting in lower basal levels. We evaluated the involvement of the ubiquitin proteasome system in mARC1 A165T degradation and observed increased ubiquitination and faster degradation of the A165T variant. In addition, we have shown that HepG2 cells carrying the MTARC1 p.A165T variant exhibit lower N-reductive activity on exogenously added amidoxime substrates in vitro. The data from these biochemical and functional assays suggest a mechanism by which the MTARC1 p.A165T variant abrogates enzyme function which may contribute to its protective effect in liver disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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47. Nanopore sequencing of influenza A and B in Oxfordshire and the United Kingdom, 2022-23.
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Cane J, Sanderson N, Barnett S, Vaughan A, Pott M, Kapel N, Morgan M, Jesuthasan G, Samuel R, Ehsaan M, Boothe H, Haduli E, Studley R, Rourke E, Diamond I, Fowler T, Watson C, Stoesser N, Walker AS, Street T, and Eyre DW
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- Humans, United Kingdom epidemiology, Female, Male, Influenza A virus genetics, Influenza A virus classification, Influenza A virus isolation & purification, Adult, Middle Aged, Adolescent, Aged, Young Adult, Child, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza A Virus, H3N2 Subtype genetics, Influenza A Virus, H3N2 Subtype isolation & purification, Influenza A Virus, H3N2 Subtype classification, Influenza, Human epidemiology, Influenza, Human virology, Nanopore Sequencing methods, Influenza B virus genetics, Influenza B virus isolation & purification, Influenza B virus classification
- Abstract
Objectives: We evaluated Nanopore sequencing for influenza surveillance., Methods: Influenza A and B PCR-positive samples from hospital patients in Oxfordshire, UK, and a UK-wide population survey from winter 2022-23 underwent Nanopore sequencing following targeted rt-PCR amplification., Results: From 941 infections, successful sequencing was achieved in 292/388 (75 %) available Oxfordshire samples: 231 (79 %) A/H3N2, 53 (18 %) A/H1N1, and 8 (3 %) B/Victoria and in 53/113 (47 %) UK-wide samples. Sequencing was more successful at lower Ct values. Most same-sample replicate sequences had identical haemagglutinin segments (124/141, 88 %); 36/39 (92 %) Illumina vs. Nanopore comparisons were identical, and 3 (8 %) differed by 1 variant. Comparison of Oxfordshire and UK-wide sequences showed frequent inter-regional transmission. Infections were closely-related to 2022-23 vaccine strains. Only one sample had a neuraminidase inhibitor resistance mutation. 849/941 (90 %) Oxfordshire infections were community-acquired. 63/88 (72 %) potentially healthcare-associated cases shared a hospital ward with ≥ 1 known infectious case. 33 epidemiologically-plausible transmission links had sequencing data for both source and recipient: 8 were within ≤ 5 SNPs, of these, 5 (63 %) involved potential sources that were also hospital-acquired., Conclusions: Nanopore influenza sequencing was reproducible and antiviral resistance rare. Inter-regional transmission was common; most infections were genomically similar. Hospital-acquired infections are likely an important source of nosocomial transmission and should be prioritised for infection prevention and control., Competing Interests: Declaration of Competing Interest No author has a conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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48. The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.
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Reilly K, Sonner S, McCay N, Rolnik DL, Casey F, Seale AN, Watson CJ, Kan A, Lai THT, Chung BHY, Diderich KEM, Srebniak MI, Dempsey E, Drury S, Giordano J, Wapner R, Kilby MD, Chitty LS, and Mone F
- Subjects
- Humans, Female, Pregnancy, Heart Defects, Congenital genetics, Heart Defects, Congenital diagnosis, Exome Sequencing methods, Prenatal Diagnosis methods
- Abstract
Objectives: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification., Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747., Results: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%)., Conclusion: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)
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- 2024
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49. Sleep disorders and criminal behavior.
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Watson C and Weiss KJ
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- Humans, Expert Testimony, Criminal Law, Crime psychology, Insanity Defense, Criminals psychology, Criminal Behavior, Sleep Wake Disorders psychology
- Abstract
Behaviors that would otherwise be considered criminal acts, but occur in the context of a sleep disorder, pose challenges to the traditional application of legal principles of criminal responsibility. Determining the degree to which consciousness is present during such behaviors becomes a necessary step in assigning criminal culpability. Historically, legal defense theories of unconsciousness, automatism, and insanity have been raised to negate culpability for parasomnia related behaviors. Accordingly, proper assessment of sleep disorders in the context of criminal charges becomes critical in assisting the functions of the justice system. This article reviews principles related to the legal tradition, expert assessment, and elements of expert testimony related to criminal behaviors and sleep disorders., (© 2024 The Authors. Behavioral Sciences & The Law published by John Wiley & Sons Ltd.)
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- 2024
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50. Causalgia: A Review of Nerve Resection, Amputation, Immunotherapy, and Amputated Limb CRPS II Pathology.
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Watson CPN, Midha R, and Ng DW
- Subjects
- Humans, Immunotherapy methods, Complex Regional Pain Syndromes surgery, Neurosurgical Procedures methods, Amputation, Surgical, Causalgia surgery
- Abstract
Background: Causalgia and complex regional pain syndrome (CRPS) type II with nerve injury can be difficult to treat. Surgical peripheral nerve denervation for causalgia has been largely abandoned by pain clinicians because of a perception that this may aggravate a central component (anesthesia dolorosa)., Methods: We selectively searched Pubmed, Cochrane, MEDLINE, EMBASE, CINAHL Plus, and Scopus from 1947 for articles, books, and book chapters for evidence of surgical treatments (nerve resection and amputation) and treatment related to autoimmunity and immune deficiency with CRPS., Results: Reviews were found for the treatment of causalgia or CRPS type II ( n = 6), causalgia relieved by nerve resection ( n = 6), and causalgia and CRPS II treated by amputation ( n = 8). Twelve reports were found of autoimmunity with CRPS, one paper of these on associated immune deficiency and autoimmunity, and two were chosen for discussion regarding treatment with immunoglobulin and one by plasma exchange. We document a report of a detailed and unique pathological examination of a CRPS type II affected amputated limb and related successful treatment with immunoglobulin., Conclusions: Nerve resection, with grafting, and relocation may relieve uncomplicated causalgia and CRPS type II in some patients in the long term. However, an unrecognized and treatable immunological condition may underly some CRPS II cases and can lead to the ultimate failure of surgical treatments.
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- 2024
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