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Purpose This study aims to examine the following across a six-month period in post-graduate research (PGR) students: mental health and well-being; the effect of academic pressures on depression, anxiety and well-being; and the extent to which psychological resilience buffered against academic pressures. Design/methodology/approach This was a longitudinal questionnaire study with predictor variables of six types of academic pressure, outcome variables of depression, anxiety and well-being, and a moderator of resilience. Findings Well-being significantly worsened across the six-month timeframe, but levels of depression and anxiety remained relatively stable. Negative perceptions of academic challenges at baseline significantly predicted anxiety, but not depression or well-being, six months later. Negative appraisals of relationships with supervisors, other university staff and work peers were not predictors of anxiety. Social support resilience which was present at baseline buffered the relationship between perceived academic challenges and anxiety. Practical implications Higher education institutions have a duty of care towards PGR students, many of whom struggle with the escalating interactions between mental health problems and academic pressures. Actively nurturing psychological resilience related to social support is key at the level of individual students and the PGR community but more broadly at an institutional level. Originality/value To the best of the authors’ knowledge, this is the first study to examine the effects of negative perceptions of multiple facets of academic life on depression, anxiety and well-being longitudinally. Additionally, it is the first study to investigate, and demonstrate, the extent to which psychological resilience can lessen the relationship between academic challenges and anxiety over time.

Background Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). Methods Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33). Findings Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules. Interpretation These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals. Funding UK Vaccine Taskforce and National Institute for Health and Care Research.

Purpose This study aimed to address three key gaps in existing knowledge about postgraduate researchers’ (PGRs) well-being. It investigated 1) the frequency and nature of depression, anxiety and well-being amongst PGRs, and relatedly, characteristics that convey vulnerability, 2) factors that impact PGR well-being, and 3) factors that influence help-seeking. Design/methodology/approach The mixed-methods design comprised quantitative and qualitative approaches. Using opportunity sampling, 585 PGRs registered at a large UK University completed an online survey. The perspectives of a purposive sample of academic and Professional Services staff (n = 61) involved in supporting PGRs were sought through in-depth focus groups and semi-structured interviews, which were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. Findings PGRs scored lower on measures of well-being and higher on measures of anxiety and depression than aged-matched groups in the general population. PGR well-being was positively affected by personal and professional relationships, and negatively affected by academic challenges and mental health problems. Academic supervisors were the primary source of support for students experiencing well-being difficulties. Thematic analysis revealed four domains that impact upon PGR well-being: postgraduate researcher identity; pressures and expectations of postgraduate research; complexity of the supervisor role; and pinch points in postgraduate research. Each domain had associations with help-seeking behaviours. Originality/value This study provides evidence that the PGR experience is perceived to be distinct from that of other students, and this helps understand sources of stress and barriers to help-seeking. It provides a steer as to how higher education institutions could better support the PGR learning experience.

Funder: Unitaid, Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19.

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe COVID-19, but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is an FDA approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modelling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase 1 trial in healthy adult participants was undertaken with high dose nitazoxanide. Participants received 1500mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose and schedule. Intensive pharmacokinetic sampling was undertaken day 1 and 5 with Cmin sampling on day 3 and 7. Fourteen healthy participants were enrolled between 18th February and 11th May 2021. All 14 doses were completed by 10/14 participants. Nitazoxanide was safe and well tolerated with no significant adverse events. Moderate gastrointestinal disturbance (loose stools) occurred in 8 participants (57.1%), with urine and sclera discolouration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on first dose and maintained throughout. Nitazoxanide administered at 1500mg BID with food was safe and well tolerated and a phase 1b/2a study is now being initiated in COVID-19 patients.

Background Little is known about the effectiveness or cost-effectiveness of interventions, such as health trainer support, to improve the health and well-being of people recently released from prison or serving a community sentence, because of the challenges in recruiting participants and following them up. Objectives This pilot trial aimed to assess the acceptability and feasibility of the trial methods and intervention (and associated costs) for a randomised trial to assess the effectiveness and cost-effectiveness of health trainer support versus usual care. Design This trial involved a pilot multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1 : 1 individual allocation to receive support from a health trainer and usual care or usual care alone, with a mixed-methods process evaluation, in 2017–18. Setting Participants were identified, screened and recruited in Community Rehabilitation Companies in Plymouth and Manchester or the National Probation Service in Plymouth. The intervention was delivered in the community. Participants Those who had been out of prison for at least 2 months (to allow community stabilisation), with at least 7 months of a community sentence remaining, were invited to participate; those who may have posed an unacceptable risk to the researchers and health trainers and those who were not interested in the trial or intervention support were excluded. Interventions The intervention group received, in addition to usual care, our person-centred health trainer support in one-to-one sessions for up to 14 weeks, either in person or via telephone. Health trainers aimed to empower participants to make healthy lifestyle changes (particularly in alcohol use, smoking, diet and physical activity) and take on the Five Ways to Well-being [Foresight Projects. Mental Capital and Wellbeing: Final Project Report. 2008. URL: www.gov.uk/government/publications/mental-capital-and-wellbeing-making-the-most-of-ourselves-in-the-21st-century (accessed 24 January 2019).], and also signposted to other options for support. The control group received treatment as usual, defined by available community and public service options for improving health and well-being. Main outcome measures The main outcomes included the Warwick–Edinburgh Mental Well-being Scale scores, alcohol use, smoking behaviour, dietary behaviour, physical activity, substance use, resource use, quality of life, intervention costs, intervention engagement and feasibility and acceptability of trial methods and the intervention. Results A great deal about recruitment was learned and the target of 120 participants was achieved. The minimum trial retention target at 6 months (60%) was met. Among those offered health trainer support, 62% had at least two sessions. The mixed-methods process evaluation generally supported the trial methods and intervention acceptability and feasibility. The proposed primary outcome, the Warwick–Edinburgh Mental Well-being Scale scores, provided us with valuable data to estimate the sample size for a full trial in which to test the effectiveness and cost-effectiveness of the intervention. Conclusions Based on the findings from this pilot trial, a full trial (with some modifications) seems justified, with a sample size of around 900 participants to detect between-group differences in the Warwick-Edinburgh Mental Well-being Scale scores at a 6-month follow-up. Future work A number of recruitment, trial retention, intervention engagement and blinding issues were identified in this pilot and recommendations are made in preparation of and within a full trial. Trial registration Current Controlled Trials ISRCTN80475744. Funding This project was funded by the National Institute for Health Research Public Health Research programme and will be published in full in Public Health Research; Vol. 7, No. 20. See the National Institute for Health Research Journals Library website for further project information.

The probation service of England and Wales has faced ongoing change to its structures and challenge to its theory and value base throughout its history. Recent years have seen an acceleration in the scope of this change with sizable budget cuts alongside the threat of competition and subsequent privitisation of probation services. This article explores whether the more fundamental but subtle challenge to practice may yet come not from explicit governmental policy, but the underlying consumerist social structures at play that operate not only in governance, but also in the mindset of the public, practitioners and probationers alike.