18 results on '"Walker NF"'
Search Results
2. A large dermoid cyst of the spermatic cord
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Pang, KH, primary, Haider, A, additional, Ho, D Heffernan, additional, Walker, NF, additional, Walkden, M, additional, Freeman, A, additional, Muneer, A, additional, and Alnajjar, HM, additional
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- 2023
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3. Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.
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Auld SC, Barczak AK, Bishai W, Coussens AK, Dewi IMW, Mitini-Nkhoma SC, Muefong C, Naidoo T, Pooran A, Stek C, Steyn AJC, Tezera L, and Walker NF
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- Animals, Humans, Congresses as Topic, Risk Factors, South Africa, Lung Diseases etiology, Lung Diseases physiopathology, Tuberculosis, Pulmonary complications, Tuberculosis, Pulmonary physiopathology
- Abstract
Post-tuberculosis (post-TB) lung disease is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to post-TB lung disease are not well understood, thus limiting the development of therapeutic interventions to improve long-term outcomes after TB. This report summarizes the work of the Pathogenesis and Risk Factors Committee for the Second International Post-Tuberculosis Symposium, which took place in Stellenbosch, South Africa, in April 2023. The committee first identified six areas with high translational potential: 1 ) tissue matrix destruction, including the role of matrix metalloproteinase dysregulation and neutrophil activity; 2 ) fibroblasts and profibrotic activity; 3 ) granuloma fate and cell death pathways; 4 ) mycobacterial factors, including pathogen burden; 5 ) animal models; and 6 ) the impact of key clinical risk factors, including HIV, diabetes, smoking, malnutrition, and alcohol. We share the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.
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- 2024
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4. Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.
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Walker NF, Schutz C, Ward A, Barr D, Opondo C, Shey M, Elkington PT, Wilkinson KA, Wilkinson RJ, and Meintjes G
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Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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5. Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.
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Burke RM, Nyirenda SK, Mtenga T, Twabi HH, Joekes E, Walker NF, Nyirenda R, Gupta-Wright A, Nliwasa M, Fielding K, MacPherson P, and Corbett EL
- Abstract
Background: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes., Methods: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample., Findings: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50)., Interpretation: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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6. Factors influencing uptake of protective behaviours by healthcare workers in England during the COVID-19 pandemic: A theory-based mixed-methods study.
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Meyer C, Crayton E, Wright A, Spyer M, Vora N, Houlihan C, Walker NF, Nastouli E, Michie S, and Lorencatto F
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- Humans, Male, Female, England epidemiology, Cross-Sectional Studies, Adult, Pandemics prevention & control, Middle Aged, SARS-CoV-2, Surveys and Questionnaires, Physical Distancing, Infection Control methods, COVID-19 prevention & control, COVID-19 epidemiology, COVID-19 psychology, Personal Protective Equipment, Health Personnel psychology
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Background: Hospital infection control policies protect patients and healthcare workers (HCWs) and limit the spread of pathogens, but adherence to COVID-19 guidance varies. We examined hospital HCWs' enactment of social distancing and use of personal protective equipment (PPE) during the COVID-19 pandemic, factors influencing these behaviours, and acceptability and feasibility of strategies to increase social distancing., Methods: An online, cross-sectional survey (n = 86) and semi-structured interviews (n = 22) with HCWs in two English hospitals during the first wave of the COVID-19 pandemic (May-December 2020). The Capability, Opportunity, Motivation (COM-B) model of behaviour change underpinned survey and topic guide questions. Spearman Rho correlations examined associations between COM-B domains and behaviours. Interviews were analysed using inductive and deductive thematic analysis. Potential strategies to improve social distancing were selected using the Behaviour Change Wheel and discussed in a stakeholder workshop (n = 8 participants)., Results: Social distancing enactment was low, with 85% of participants reporting very frequently or always being in close contact with others in communal areas. PPE use was high (88% very frequently or always using PPE in typical working day). Social distancing was associated with Physical Opportunity (e.g., size of physical space), Psychological Capability (e.g., clarity of guidance), and Social Opportunity (e.g., support from managers). Use of PPE was associated with Psychological Capability (e.g., training), Physical Opportunity (e.g., availability), Social Opportunity (e.g., impact on interactions with patients), and Reflective Motivation (e.g., beliefs that PPE is effective). Local champions and team competition were viewed as feasible strategies to improve social distancing., Conclusions: It is valuable to understand and compare the drivers of individual protective behaviours; when faced with the same level of perceived threat, PPE use was high whereas social distancing was rarely enacted. Identified influences represent targets for intervention strategies in response to future infectious disease outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Meyer 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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7. Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers.
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Schiff HF, Walker NF, Ugarte-Gil C, Tebruegge M, Manousopoulou A, Garbis SD, Mansour S, Wong PHM, Rockett G, Piazza P, Niranjan M, Vallejo AF, Woelk CH, Wilkinson RJ, Tezera LB, Garay-Baquero D, and Elkington P
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- Humans, Male, Female, Adult, Mycobacterium tuberculosis, Middle Aged, Peru epidemiology, South Africa epidemiology, Case-Control Studies, Sensitivity and Specificity, Biomarkers blood, Proteomics methods, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary blood
- Abstract
BACKGROUNDNovel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections.METHODSWe applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modeling and network correlation analyses identified 118 differentially expressed proteins, significant through 3 complementary analytical pipelines. Candidate biomarkers were subsequently analyzed in 2 validation cohorts of differing ethnicity using antibody-based proximity extension assays.RESULTSTB-specific host biomarkers were confirmed. A 6-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14, and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts.CONCLUSIONThis biomarker panel exceeds the World Health Organization Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.FUNDINGMedical Research Council (MRC) (MR/R001065/1, MR/S024220/1, MR/P023754/1, and MR/W025728/1); the MRC and the UK Foreign Commonwealth and Development Office; the UK National Institute for Health Research (NIHR); the Wellcome Trust (094000, 203135, and CC2112); Starter Grant for Clinical Lecturers (Academy of Medical Sciences UK); the British Infection Association; the Program for Advanced Research Capacities for AIDS in Peru at Universidad Peruana Cayetano Heredia (D43TW00976301) from the Fogarty International Center at the US NIH; the UK Technology Strategy Board/Innovate UK (101556); the Francis Crick Institute, which receives funding from UKRI-MRC (CC2112); Cancer Research UK (CC2112); and the NIHR Biomedical Research Centre of Imperial College NHS.
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- 2024
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8. Perspectives from the 2 nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes.
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Allwood BW, Nightingale R, Agbota G, Auld S, Bisson GP, Byrne A, Dunn R, Evans D, Hoddinott G, Günther G, Islam Z, Johnston JC, Kalyatanda G, Khosa C, Marais S, Makanda G, Mashedi OM, Meghji J, Mitnick C, Mulder C, Nkereuwem E, Nkereuwem O, Ozoh OB, Rachow A, Romanowski K, Seddon JA, Schoeman I, Thienemann F, Walker NF, Wademan DT, Wallis R, and van der Zalm MM
- Abstract
In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2
nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions., (© 2024 The Authors.)- Published
- 2024
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9. Elevated plasma matrix metalloproteinases associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosis.
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Walker NF, Schutz C, Ward A, Barr D, Opondo C, Shey M, Elkington PT, Wilkinson KA, Wilkinson RJ, and Meintjes G
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Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality and Mycobacterium tuberculosis ( Mtb) blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb -BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated with Mtb -BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB., Competing Interests: Conflicts of Interest All authors: No conflicts of interest to declare.
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- 2023
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10. A 'train the trainers' approach to infection prevention and control training in pandemic conditions.
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Haigh KA, Liuzzi F, Irvine S, Thompson A, Hepworth E, Hoyle MC, Cruise J, Hine P, and Walker NF
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Background: The first wave of the SARS-CoV-2 global pandemic in early 2020 required a rapid roll-out of infection prevention and control (IPC) training for healthcare workers (HCW), including use of appropriate personal protective equipment (PPE). Education about respiratory droplet and aerosol transmission was of paramount importance to ensure safe working practices and improve confidence., Methods: A joint working group of Infectious Diseases and IPC staff developed a 'train the trainers' programme, to be rapidly deployed over a three-week period. This model utilised a snowballing approach, training selected staff with the intention that they would train their teams, facilitating swift cascading of information. Targeted invitations prompted staff from diverse departments of the hospital to attend. Pre- and post-session questionnaires evaluated staff confidence with regard to appropriate PPE use., Results: The programme trained 130 HCW over a three week period, was well received and led to increased confidence with PPE use amongst staff. Real-time evaluation ensured content could be adapted to the specific needs of HCW involved. We highlight perceived gaps in training despite existing and enhanced training structures., Conclusion: Provision of face-to-face training in transmission-based precautions, including PPE use, is required to maintain confidence in safe and appropriate IPC amongst hospital staff. We highlight the importance of including non-clinical staff in PPE educational programmes, recognising that these roles are vital for patient care and are frequently patient-facing. We recommend adopting the train the trainers model to facilitate rapid dissemination of education, with interactive multidisciplinary training in future outbreaks to improve HCW confidence and effective IPC., Competing Interests: 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., (© 2023 The Authors.)
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- 2023
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11. Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi.
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Gordon SB, Sichone S, Chirwa AE, Hazenberg P, Kafuko Z, Ferreira DM, Flynn J, Fortune S, Balasingam S, Biagini GA, McShane H, Mwandumba HC, Jambo K, Dedha K, Raj Sharma N, Robertson BD, Walker NF, and Morton B
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Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3
rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations. Registration: PROSPERO ( CRD42022302785; 21 January 2022)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Gordon SB et al.)- Published
- 2023
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12. Clinical characteristics and management of neurocysticercosis patients: a retrospective assessment of case reports from Europe.
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Stelzle D, Abraham A, Kaminski M, Schmidt V, De Meijere R, Bustos JA, Garcia HH, Sahu PS, Bobić B, Cretu C, Chiodini P, Dermauw V, Devleesschauwer B, Dorny P, Fonseca A, Gabriël S, Morales MÁG, Laranjo-González M, Hoerauf A, Hunter E, Jambou R, Jurhar-Pavlova M, Reiter-Owona I, Sotiraki S, Trevisan C, Vilhena M, Walker NF, Zammarchi L, and Winkler AS
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- Animals, Humans, Retrospective Studies, Europe, Prevalence, Neurocysticercosis diagnosis, Neurocysticercosis drug therapy, Neurocysticercosis epidemiology, Taenia solium
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Objectives: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe., Methods: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available., Results: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases., Conclusions: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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13. Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: An observational cohort study.
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Walker NF, Byrne RL, Howard A, Nikolaou E, Farrar M, Glynn S, Cheliotis KS, Cubas Atienzar AI, Davies K, Reiné J, Rashid-Gardner Z, German EL, Solórzano C, Blandamer T, Hitchins L, Myerscough C, Gessner BD, Begier E, Collins AM, Beadsworth M, Todd S, Hill H, Houlihan CF, Nastouli E, Adams ER, Mitsi E, and Ferreira DM
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- Humans, SARS-CoV-2, Cohort Studies, Retrospective Studies, State Medicine, Health Personnel, Specimen Handling, Nasopharynx, Saliva, COVID-19 diagnosis
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Background: The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control., Methods: Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour., Results: Over a 12-week period from 30th March 2020, 40·0% (n = 34/85, 95% confidence interval 31·3-51·8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47·1% (n = 40) and self-isolation by 25·9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29·4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93·4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35·0% (n = 7/20) were positive exclusively by OP/NP swab, 40·0% (n = 8/20) exclusively by saliva and in only 25·0% (n = 5/20) were the OP/NP and saliva result both positive., Conclusions: HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab sampling would improve detection of SARS-CoV-2 for surveillance and is recommended for a high sensitivity strategy., Competing Interests: EB and BDG hold Pfizer stock as Pfizer employees. No other relationships or activities exist that could appear to have influenced the submitted work. Sources of grant funding are stated (see Financial Disclosures) and affiliations given for each author., (Copyright: © 2023 Walker 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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- 2023
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14. Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.
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Walker NF, Karim F, Moosa MYS, Moodley S, Mazibuko M, Khan K, Sterling TR, van der Heijden YF, Grant AD, Elkington PT, Pym A, and Leslie A
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- Biomarkers, Humans, Mycobacterium tuberculosis, Sputum, Matrix Metalloproteinase 8 blood, Tuberculosis, Pulmonary complications, Tuberculosis, Pulmonary diagnosis
- Abstract
Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2022
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15. Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2.
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Mitsi E, Reiné J, Urban BC, Solórzano C, Nikolaou E, Hyder-Wright AD, Pojar S, Howard A, Hitchins L, Glynn S, Farrar MC, Liatsikos K, Collins AM, Walker NF, Hill HC, German EL, Cheliotis KS, Byrne RL, Williams CT, Cubas-Atienzar AI, Fletcher TE, Adams ER, Draper SJ, Pulido D, Beavon R, Theilacker C, Begier E, Jodar L, Gessner BD, and Ferreira DM
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- Health Personnel, Humans, Immunity, Streptococcus pneumoniae, COVID-19, SARS-CoV-2
- Abstract
BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.MethodsHere, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.ResultsIn both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.ConclusionOur findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registrationISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).
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- 2022
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16. Pre-prostatectomy membranous urethral length as a predictive factor of post prostatectomy incontinence requiring surgical intervention with an artificial urinary sphincter or a male sling.
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Oza P, Walker NF, Rottenberg G, MacAskill F, Malde S, Taylor C, and Sahai A
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- Humans, Male, Prostatectomy adverse effects, Treatment Outcome, Urethra surgery, Suburethral Slings, Urinary Incontinence etiology, Urinary Incontinence surgery, Urinary Sphincter, Artificial
- Abstract
Aims: To ascertain whether the membranous urethral length (MUL) is predictive of postprostatectomy incontinence (PPI) that requires surgery such as artificial urinary sphincter (AUS) or male sling (MS)., Methods: Men who had undergone AUS or MS for PPI were identified from a prospectively maintained database and compared to a control group of men who were continent at 12 months after radical prostatectomy. MUL in sagittal and coronal planes, sphincter height and width were measured on prebiopsy T2-weighted MRI scans. Sphincter volume was estimated as an ellipsoid cylinder., Results: A total of 95 patients (64 AUS and 31 MS) were compared to 60 continent controls. There was no statistical difference in presenting PSA, prostate volume, and T-stage. The mean MUL in sagittal and coronal planes was 11.31 mm (SD: 2.6, range: 6-17 mm) and 11.43 mm (SD: 2.94, range: 5-17 mm) in patients who had AUS and MS, respectively; 15.23 mm (SD: 4.2, range: 8.25-25 mm) and 15.75 mm (SD: 4.1, range: 8-24 mm) in controls (p < 0.01). No men in the PPI surgery group had an MUL >17 mm compared to 35% (20/57 sagittal, 20/58 coronal) of controls. The odds ratio for requiring surgery for PPI was 13.4 for sagittal MUL <9 mm and 3.2 if the MUL <12 mm., Conclusions: Patients who had surgery for PPI had a significantly shorter MUL and sphincter volume than continent controls. Men with an MUL >17 mm are unlikely to require surgery for PPI whereas an MUL <12 mm significantly increases the risk of requiring surgery for PPI. MUL should be considered when discussing treatment options for prostate cancer., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)
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- 2022
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17. Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016-2019.
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Gray KL, Kiazolu M, Jones J, Konstantinova A, Zawolo JSW, Gray WH, Walker NF, Garbo JT, Caldwell S, Odo M, Bhadelia N, DeMarco J, and Skrip LA
- Abstract
Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The "Treat all" strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 -December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30-45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8-51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21-2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51-3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35-44 (aHR 0.65, 95%CI: 0.44-0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39-0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53-3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75-3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57-6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51-0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20-0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects-average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06-1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11-2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01-0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004-0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Gray 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.)
- Published
- 2022
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18. Spontaneous ureteric rupture due to high pressure chronic retention.
- Author
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Deen S, Ogbu E, Walker NF, and Nkwam NM
- Abstract
Spontaneous ureteric rupture is a rare phenomenon which can be traumatic or non-traumatic that may arise from ureteric obstruction, trauma, mucosal inflammation from urolithiasis, connective tissue disease or retroperitoneal fibrosis. High pressure chronic retention is characterised by noctural enuresis, a tense palpable bladder, hypertension, progressive renal impairment, bilateral hydronephrosis and hydroureter on imaging. Obstructive urological symptoms are typically absent in uncomplicated cases. We report the case of a 69-year-old male who presented with high pressure chronic retention and spontaneous ureteric rupture demonstrated on a noncontrast CT. This patient was managed with a urethral catheter on free drainage and a retrograde ureteric stent. The patient's condition improved, and the stent was removed after a uretero-pyeloscopy which revealed no extravasation. He later underwent a successful transurethral resection of the prostate., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
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