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Research outputs from the Pharmacy Department at the RD&E


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Now showing 1 - 5 of 10
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    Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial
    (Elsevier, 2023-07-01) Liu, X.; Munro, A. P. S.; Wright, A.; Feng, S.; Janani, L.; Aley, P. K.; Babbage, G.; Baker, J.; Baxter, D.; Bawa, T.; Bula, M.; Cathie, K.; Chatterjee, K.; Dodd, K.; Enever, Y.; Fox, L.; Qureshi, E.; Goodman, A. L.; Green, C. A.; Haughney, J.; Hicks, A.; Jones, C. E.; Kanji, N.; van der Klaauw, A. A.; Libri, V.; Llewelyn, M. J.; Mansfield, R.; Maallah, M.; McGregor, A. C.; Minassian, A. M.; Moore, P.; Mughal, M.; Mujadidi, Y. F.; Belhadef, H. T.; Holliday, K.; Osanlou, O.; Osanlou, R.; Owens, D. R.; Pacurar, M.; Palfreeman, A.; Pan, D.; Rampling, T.; Regan, K.; Saich, S.; Saralaya, D.; Sharma, S.; Sheridan, R.; Stokes, M.; Thomson, E. C.; Todd, S.; Twelves, C.; Read, R. C.; Charlton, S.; Hallis, B.; Ramsay, M.; Andrews, N.; Lambe, T.; Nguyen-Van-Tam, J. S.; Cornelius, V.; Snape, M. D.; Faust, S. N.
    BACKGROUND: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. METHODS: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. RESULTS: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. CONCLUSIONS: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.
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    Tipping the balance: A systematic review and meta-ethnography to unfold the complexity of surgical antimicrobial prescribing behavior in hospital settings
    (PLoS One, 2022-07-21) Parker, H.; Frost, J.; Day, J.; Bethune, R.; Kajamaa, A.; Hand, K.; Robinson, S.; Mattick, K.
    Surgical specialties account for a high proportion of antimicrobial use in hospitals, and misuse has been widely reported resulting in unnecessary patient harm and antimicrobial resistance. We aimed to synthesize qualitative studies on surgical antimicrobial prescribing behavior, in hospital settings, to explain how and why contextual factors act and interact to influence practice. Stakeholder engagement was integrated throughout to ensure consideration of varying interpretive repertoires and that the findings were clinically meaningful. The meta-ethnography followed the seven phases outlined by Noblit and Hare. Eight databases were systematically searched without date restrictions. Supplementary searches were performed including forwards and backwards citation chasing and contacting first authors of included papers to highlight further work. Following screening, 14 papers were included in the meta-ethnography. Repeated reading of this work enabled identification of 48 concepts and subsequently eight overarching concepts: hierarchy; fear drives action; deprioritized; convention trumps evidence; complex judgments; discontinuity of care; team dynamics; and practice environment. The overarching concepts interacted to varying degrees but there was no consensus among stakeholders regarding an order of importance. Further abstraction of the overarching concepts led to the development of a conceptual model and a line-of-argument synthesis, which posits that social and structural mediators influence individual complex antimicrobial judgements and currently skew practice towards increased and unnecessary antimicrobial use. Crucially, our model provides insights into how we might 'tip the balance' towards more evidence-based antimicrobial use. Currently, healthcare workers deploy antimicrobials across the surgical pathway as a safety net to allay fears, reduce uncertainty and risk, and to mitigate against personal blame. Our synthesis indicates that prescribing is unlikely to change until the social and structural mediators driving practice are addressed. Furthermore, it suggests that research specifically exploring the context for effective and sustainable quality improvement stewardship initiatives in surgery is now urgent.
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    Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder
    (American Psychiatric Publishing, 2022-01-11) Grabski, M.; McAndrew, A.; Lawn, W.; Marsh, B.; Raymen, L.; Stevens, T.; Hardy, L.; Warren, F.; Bloomfield, M.; Borissova, A.; Maschauer, E.; Broomby, R.; Price, R.; Coathup, R.; Gilhooly, D.; Palmer, E.; Gordon-Williams, R.; Hill, R.; Harris, J.; Mollaahmetoglu, O. M.; Curran, H. V.; Brandner, B.; Lingford-Hughes, A.; Morgan, C. J. A.
    OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.
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    Understanding surgical antimicrobial prescribing behaviour in the hospital setting: a systematic review and meta-ethnography protocol
    (BioMed Central, 2020-10-10) Parker, Hazel; Britten, Nicky; Mattick, K.
    Background: Surgical specialities use extensive amounts of antimicrobials, and misuse has been widely reported, making them a key target for antimicrobial stewardship initiatives. Interventions informed by, and tailored to, a clear understanding of the contextual barriers to appropriate antimicrobial use are more likely to successfully improve practice. However, this approach has been under utilised. Our aim is to synthesise qualitative studies on surgical antimicrobial prescribing behaviour (APB) in hospital settings to explain how and why contextual factors act and interact to influence APB amongst surgical teams. We will develop new theory to advance understanding and identify knowledge gaps to inform further research. Methods: The meta-ethnography will follow the seven-phase method described by Noblit and Hare. We will conduct a comprehensive search using eight databases (AMED, CINAHL, EMBASE, MEDLINE, MEDLINE-in-process, Web of Science, Cochrane Library and PsycINFO) with no date restrictions; forwards and backwards citation searches; and contacting first authors of relevant papers. Studies will be dual screened and included if they use recognised qualitative methods and analysis; focus on contextual factors associated with surgical APB within hospital settings; are available in full in English; and are relevant to the research question. Any disagreements between reviewers will be resolved through discussion to reach consensus. Included studies will be read repeatedly to illuminate key concepts and the relationship between key concepts across studies. Then, key concepts will be sorted into conceptual categories or 'piles' which will be further abstracted to form a conceptual framework explaining surgical APB. During the synthesis, emerging interpretations will be discussed with stakeholders (including authors of included studies where possible; surgical and stewardship practitioners; and patient representatives) to ensure new knowledge is meaningful. Discussion: This research has several strengths: (1) the protocol has been written with reference to established guidance maximising rigour and transparency; (2) the multi-disciplinary research team bring varied interpretative repertoires and relevant methodological skills; and (3) stakeholders will be involved to ensure that findings are relevant, and disseminated via suitable channels, to support improved patient care.
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    Trainee doctors' experiences of common problems in the antibiotic prescribing process: an activity theory analysis of narrative data from UK hospitals
    (BMJ, 2019-06) Parker, Hazel
    Prescribing antibiotics is an error-prone activity and one of the more challenging responsibilities for doctors in training. The nature and extent of challenges experienced by them at different stages of the antibiotic prescribing process are not well described, meaning that interventions may not target the most problematic areas.