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  1. Article ; Online: Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study.

    Murrell, Isa / Forde, Donall / Zelek, Wioleta / Tyson, Linda / Chichester, Lisa / Palmer, Nicki / Jones, Rachel / Morgan, B Paul / Moore, Catherine

    PloS one

    2021  Volume 16, Issue 1, Page(s) e0245382

    Abstract: Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of ... ...

    Abstract Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform the best use of serological assays for diagnostic testing and serosurveillance studies. Here, we describe the humoral responses in a cohort of hospitalised COVID-19 patients (n = 19) shortly following the onset of symptoms. Commercial and 'in-house' serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens-Spike (S) S1 sub-unit and Nucleocapsid protein (NP)-and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). Antibody response kinetics varied amongst the cohort, with patients seroconverting within 1 week, between 1-2 weeks, or after 2 weeks, following symptom onset. Anti-NP IgG responses were generally detected earlier, but reached maximum levels slower, than anti-S1 IgG responses. The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2. These data revealed events and patterns of SARS-CoV-2 seroconversion that may be important predictors of the outcome of infection and guide the delivery of clinical services in the COVID-19 response.
    MeSH term(s) Aged ; Aged, 80 and over ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; Cohort Studies ; Coronavirus Nucleocapsid Proteins/chemistry ; Female ; Hospitalization ; Humans ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Phosphoproteins/chemistry ; SARS-CoV-2/chemistry ; Seroconversion ; Spike Glycoprotein, Coronavirus/chemistry ; Wales
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Coronavirus Nucleocapsid Proteins ; Immunoglobulin G ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-01-26
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0245382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reaching people receiving opioid agonist therapy at community pharmacies with hepatitis C virus: an international randomised controlled trial.

    Byrne, Christopher J / Radley, Andrew / Inglis, Sarah K / Beer, Lewis / Palmer, Nicki / Duc Pham, Minh / Allardice, Kate / Wang, Huan / Robinson, Emma / Hermansson, Monika / Semizarov, Dimitri / Healy, Brendan / Doyle, Joseph S / Dillon, John F

    Alimentary pharmacology & therapeutics

    2022  Volume 55, Issue 12, Page(s) 1512–1523

    Abstract: Background: Conventional healthcare models struggle to engage those at risk of hepatitis C virus (HCV) infection. This international study evaluated point-of-care (PoC) HCV RNA diagnostic outreach and direct-acting antiviral (DAA) treatment for ... ...

    Abstract Background: Conventional healthcare models struggle to engage those at risk of hepatitis C virus (HCV) infection. This international study evaluated point-of-care (PoC) HCV RNA diagnostic outreach and direct-acting antiviral (DAA) treatment for individuals receiving opioid agonist therapy (OAT) in community pharmacies.
    Aims: We assessed the effectiveness of a roving nurse-led pathway offering PoC HCV RNA testing to OAT clients in community pharmacies relative to conventional care.
    Methods: Pharmacies in Scotland, Wales, and Australia were randomised to provide PoC HCV RNA testing or conventional referral. Pharmacists directed OAT clients to on-site nurses (intervention) or local clinics (control). Infected participants were treated with DAAs, alongside OAT. Primary outcome was the number of participants with sustained virologic response at 12 weeks (SVR) and analysed using mixed effects logistic regression in the intention-to-treat (ITT) population.
    Results: Forty pharmacies were randomised. The ITT population contained 1410 OAT clients. In the conventional arm (n = 648), 62 (10%) agreed to testing, 17 (27%) were tested, 6 (35%) were positive and 5 (83%) initiated treatment. In the intervention arm (n = 762), 148 (19%) agreed to testing, 144 (97%) were tested, 23 (16%) were positive and 22 (96%) initiated treatment. SVR was obtained by 2 (40%; conventional) and 18 (82%; intervention). Intervention arm participants had higher odds of testing, OR 16.95 (7.07-40.64, p < 0.001); treatment, OR 4.29 (1.43-12.92, p = 0.010); and SVR, OR 8.64 (1.82-40.91, p = 0.007).
    Conclusions: Nurse-led PoC diagnosis in pharmacies made HCV care more accessible for OAT clients relative to conventional care. However, strategies to improve testing uptake are required.
    Trial registration: NCT03935906.
    MeSH term(s) Analgesics, Opioid/therapeutic use ; Antiviral Agents/therapeutic use ; Hepacivirus ; Hepatitis C/drug therapy ; Hepatitis C, Chronic/diagnosis ; Hepatitis C, Chronic/drug therapy ; Humans ; Pharmacies ; RNA/therapeutic use ; Substance Abuse, Intravenous/drug therapy ; Substance Abuse, Intravenous/epidemiology
    Chemical Substances Analgesics, Opioid ; Antiviral Agents ; RNA (63231-63-0)
    Language English
    Publishing date 2022-05-10
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 639012-2
    ISSN 1365-2036 ; 0269-2813 ; 0953-0673
    ISSN (online) 1365-2036
    ISSN 0269-2813 ; 0953-0673
    DOI 10.1111/apt.16953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: R

    Byrne, Christopher / Radley, Andrew / Inglis, Sarah Karen / Beer, Lewis J Z / Palmer, Nicki / Pham, Minh Duc / Healy, Brendan / Doyle, Joseph S / Donnan, Peter / Dillon, John F

    BMJ open

    2020  Volume 10, Issue 8, Page(s) e036501

    Abstract: Introduction: Hepatitis C virus (HCV) is a global public health threat, and novel models of care are required to treat those currently or previously at highest risk of infection, particularly persons who inject drugs (PWID; ever injected), as ... ...

    Abstract Introduction: Hepatitis C virus (HCV) is a global public health threat, and novel models of care are required to treat those currently or previously at highest risk of infection, particularly persons who inject drugs (PWID; ever injected), as conventional healthcare models do not have the reach to deliver cure of HCV to disadvantaged, disproportionately affected communities. In Western Europe and Australasia, it is estimated that HCV affects between 0.4% and 1.0% of the regions' populations, accordingly, it affects between 0.4% and 0.7% of the populations of countries in this study (Scotland, Wales and Australia).
    Methods and analysis: REACH HCV is an international multicentre cluster randomised controlled trial with sites in Scotland, Wales and Australia. The sites are community pharmacies which are randomised equally to one of two pathways: the pharmacy intervention pathway or the education-only (control) pathway. Participants are recruited from OST clients in these pharmacies.In the pharmacy intervention pathway, participants receive a rapid point-of-care HCV PCR test in their pharmacy by a study outreach nurse. If positive, direct-acting antivirals (DAAs) are delivered to participants via their pharmacist in line with their OST schedule.In the education-only pathway, pharmacists counsel OST clients on HCV and refer them to the nearest nurse-led clinic or general practitioner offering HCV testing according to standard care protocols. If positive, DAAs are delivered as in the intervention pathway.The primary endpoint for both pathways is sustained viral response at 12 weeks post-treatment . Secondary outcomes are: cost-efficacy by pathway; participants tested by pathway; adherence to therapy by pathway and impact of blood test results on treatment decisions.A statistical analysis plan will be finalised prior to data lock. Analysis will be by intention to treat (ITT) to show superiority. Modified ITT analysis will also be undertaken to explore the steps in the pathways.
    Ethics and dissemination: The trial received ethical favourable opinion from the East of Scotland Research Ethics Committee 2 (19/ES/0025) for UK sites and approval from the Alfred Hospital Ethics Committee (148/19) for Australian sites and complies with principles of Good Clinical Practice. Final results will be presented in peer-reviewed journals and at relevant conferences.
    Trial registration number: ClinicalTrials.gov Registry NCT03935906.
    Protocol version: V.4.0-19 March 2020.
    MeSH term(s) Antiviral Agents/therapeutic use ; Australasia ; Australia ; Drug Users ; Europe ; Hepacivirus ; Hepatitis C/diagnosis ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Hepatitis C, Chronic/drug therapy ; Humans ; Methadone/therapeutic use ; Pharmacies ; Randomized Controlled Trials as Topic ; Scotland ; Substance Abuse, Intravenous/drug therapy ; Wales
    Chemical Substances Antiviral Agents ; Methadone (UC6VBE7V1Z)
    Language English
    Publishing date 2020-08-30
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2019-036501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospitals laboratory workers with validation of DBS specimen analysis.

    Murrell, Isa / Forde, Donall / Tyson, Linda / Chichester, Lisa / Garratt, Anna / Vineall, Owen / Palmer, Nicki / Jones, Rachel / Moore, Catherine

    medRxiv

    Keywords covid19
    Language English
    Publishing date 2020-11-03
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.10.29.20219931
    Database COVID19

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  5. Article ; Online: A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospitals laboratory workers with validation of DBS specimen analysis

    Murrell, Isa / Forde, Donall / Tyson, Linda / Chichester, Lisa / Garratt, Anna / Vineall, Owen / Palmer, Nicki / Jones, Rachel / Moore, Catherine

    Abstract: There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent ... ...

    Abstract There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent public health response. As experience of commercial assays increases, so too does knowledge of their precision and limitations. Here we present our experience of these systems thus far. We perform a spot sero-prevalence study amongst staff in a tertiary hospitals clinical microbiology laboratory, before undertaking validation of DBS serological testing as an alternate specimen for analysis. Finally, we characterise the spike and nucleocapsid antibody response over 160 days post a positive PCR test in nine non-hospitalised staff members. Amongst a cohort of 195 staff, 17 tested positive for SARS-CoV-2 antibodies (8.7%). Self-reporting of SARS-CoV2 infection (P=<0.0001) and testing of a household contact (P = 0.027) were significant variables amongst the positive and negative sub-groups. Testing of 28 matched serum and DBS samples demonstrated 96% accuracy between the sample types. A differential rate of decline of SARS-CoV-2 antibodies against nucleocapsid or spike protein was observed. At 4 months post a positive PCR test 7/9 (78%) individuals had detectable antibodies against spike protein, but only 2/9 (22%) had detectable antibodies against nucleocapsid protein. This study reveals a broad agreement amongst commercial platforms tested and suggests the use of DBS as an alternate specimen option to enable widespread population testing for SARS-CoV-2 antibodies. These results suggest potential limitations of these platforms in estimating historical infection. By setting this temporal point of reference for this cohort of non-patient facing laboratory staff, future exposure risks and mitigation strategies can be evaluated more fully.
    Keywords covid19
    Publisher MedRxiv; WHO
    Document type Article ; Online
    Note WHO #Covidence: #20219931
    DOI 10.1101/2020.10.29.20219931
    Database COVID19

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  6. Article ; Online: Temporal Development and Neutralising Ability of Antibodies Against SARS-CoV-2 in Hospitalised COVID-19 Patients

    Murrell, Isa Imanial / Forde, Donall / Zelek, Wioleta / Tyson, Linda / Chichester, Lisa / Palmer, Nicki / Jones, R / Morgan, B.P. / Moore, C

    SSRN Electronic Journal ; ISSN 1556-5068

    An Observational Cohort Study

    2020  

    Keywords covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.2139/ssrn.3666842
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Respiratory pathogen colonization of dental plaque, the lower airways, and endotracheal tube biofilms during mechanical ventilation.

    Sands, Kirsty M / Wilson, Melanie J / Lewis, Michael A O / Wise, Matt P / Palmer, Nicki / Hayes, Anthony J / Barnes, Rosemary A / Williams, David W

    Journal of critical care

    2017  Volume 37, Page(s) 30–37

    Abstract: Purpose: In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary ... ...

    Abstract Purpose: In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients.
    Materials and methods: Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay.
    Results: A "microbial shift" occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms.
    Conclusions: To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Biofilms ; Carrier State/microbiology ; Critical Illness ; DNA, Bacterial/analysis ; Dental Plaque/microbiology ; Female ; Humans ; Intubation, Intratracheal/instrumentation ; Lung/microbiology ; Male ; Microbiota/genetics ; Middle Aged ; Pneumonia, Ventilator-Associated/microbiology ; Pseudomonas aeruginosa/genetics ; Respiration, Artificial ; Staphylococcus aureus/genetics ; Ventilators, Mechanical ; Young Adult
    Chemical Substances DNA, Bacterial
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632818-0
    ISSN 1557-8615 ; 0883-9441
    ISSN (online) 1557-8615
    ISSN 0883-9441
    DOI 10.1016/j.jcrc.2016.07.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Comparison of foam swabs and toothbrushes as oral hygiene interventions in mechanically ventilated patients: a randomised split mouth study.

    Marino, Paola J / Hannigan, Ailish / Haywood, Sean / Cole, Jade M / Palmer, Nicki / Emanuel, Charlotte / Kinsella, Tracey / Lewis, Michael A O / Wise, Matt P / Williams, David W

    BMJ open respiratory research

    2016  Volume 3, Issue 1, Page(s) e000150

    Abstract: Introduction: During critical illness, dental plaque may serve as a reservoir of respiratory pathogens. This study compared the effectiveness of toothbrushing with a small-headed toothbrush or a foam-headed swab in mechanically ventilated patients.: ... ...

    Abstract Introduction: During critical illness, dental plaque may serve as a reservoir of respiratory pathogens. This study compared the effectiveness of toothbrushing with a small-headed toothbrush or a foam-headed swab in mechanically ventilated patients.
    Methods: This was a randomised, assessor-blinded, split-mouth trial, performed at a single critical care unit. Adult, orally intubated patients with >20 teeth, where >24 hours of mechanical ventilation was expected were included. Teeth were cleaned 12-hourly using a foam swab or toothbrush (each randomly assigned to one side of the mouth). Cleaning efficacy was based on plaque scores, gingival index and microbial plaque counts.
    Results: High initial plaque (mean=2.1 (SD 0.45)) and gingival (mean=2.0 (SD 0.54)) scores were recorded for 21 patients. A significant reduction compared with initial plaque index occurred using both toothbrushes (mean change=-1.26, 95% CI -1.57 to -0.95; p<0.001) and foam swabs (mean change=-1.28, 95% CI -1.54 to -1.01; p<0.001). There was significant reduction in gingival index over time using toothbrushes (mean change=-0.92; 95% CI -1.19 to -0.64; p<0.001) and foam swabs (mean change=-0.85; 95% CI -1.10 to -0.61; p<0.001). Differences between cleaning methods were not statistically significant (p=0.12 for change in gingival index; p=0.24 for change in plaque index). There was no significant change in bacterial dental plaque counts between toothbrushing (mean change 3.7×10
    Conclusions: Patients admitted to adult intensive care had poor oral health, which improved after brushing with a toothbrush or foam swab. Both interventions were equally effective at removing plaque and reducing gingival inflammation.
    Trial registration number: NCT01154257; Pre-results.
    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article
    ZDB-ID 2736454-9
    ISSN 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2016-000150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C.

    Lilja, Gisela / Nielsen, Niklas / Friberg, Hans / Horn, Janneke / Kjaergaard, Jesper / Nilsson, Fredrik / Pellis, Tommaso / Wetterslev, Jørn / Wise, Matt P / Bosch, Frank / Bro-Jeppesen, John / Brunetti, Iole / Buratti, Azul Forti / Hassager, Christian / Hofgren, Caisa / Insorsi, Angelo / Kuiper, Michael / Martini, Alice / Palmer, Nicki /
    Rundgren, Malin / Rylander, Christian / van der Veen, Annelou / Wanscher, Michael / Watkins, Helen / Cronberg, Tobias

    Circulation

    2015  Volume 131, Issue 15, Page(s) 1340–1349

    Abstract: Background: Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been ... ...

    Abstract Background: Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general.
    Methods and results: Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar.
    Conclusions: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest.
    Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01946932.
    MeSH term(s) Aged ; Body Temperature/physiology ; Cognition/physiology ; Electrocardiography ; Europe ; Female ; Follow-Up Studies ; Humans ; Hypothermia, Induced/methods ; Male ; Middle Aged ; Myocardial Infarction/physiopathology ; Myocardial Infarction/therapy ; Out-of-Hospital Cardiac Arrest/physiopathology ; Out-of-Hospital Cardiac Arrest/therapy ; Patient Outcome Assessment ; Risk Factors ; Treatment Outcome
    Language English
    Publishing date 2015-04-14
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.114.014414
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