North Bristol NHS Trust

About: North Bristol NHS Trust is a healthcare organization based out in Bristol, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 2204 authors who have published 2811 publications receiving 61110 citations.

Anoctamin-1 in the Juvenile Rat Urinary Bladder

Abstract: Purpose To investigate presence, location and functional role of calcium-activated chloride channel (CaCC) Anoctamin-1 (Ano1) in rat urinary bladder.

Pharmacodynamics of Razupenem (PZ601) Studied in an In Vitro Pharmacokinetic Model of Infection

Abstract: Simulations of administration of razupenem at 1 g every 12 h by 1-h intravenous (i.v.) infusion were performed in an in vitro pharmacokinetic model of infection. The antibacterial effect of this razupenem dosing regimen against six strains of Staphylococcus aureus (one methicillin-sensitive S. aureus [MSSA] strain [MIC, 0.015 μg/ml] and five methicillin-resistant S. aureus [MRSA] strains [MIC range, 0.09 to 3 μg/ml]) and five strains of Enterobacteriaceae (three Escherichia coli strains [two containing extended-spectrum β-lactamases {ESBLs}] and two Enterobacter sp. strains [one with an AmpC enzyme and the other with a raised razupenem MIC; MIC range, 0.09 to 6 μg/ml]) was assessed. Against the MSSA and MRSA strains, razupenem produced a >3.5-log-unit reduction in viable count after 24 h. There were no changes in population profiles. In a second series of experiments, over 5 days there was rapid initial clearance of MRSA from the model followed by regrowth after 48 h. MRSA colonies appeared on 2× MIC recovery medium after 72 h with strain 33820 (MIC, 3.0 μg/ml) and at 120 h with strain 27706 (MIC, 1.5 μg/ml). Against E. coli and Enterobacter spp., razupenem produced a >3.5-log-unit reduction in bacterial counts for all strains except that with an MIC of 6 μg/ml, where razupenem had a notably poorer antibacterial effect. Population profiles were unchanged after 48 h of exposure to razupenem except for Enterobacter strain 34425 (MIC, 6.0 μg/ml), where colonies were recovered from media containing 2×, 4×, and 8× MIC. In dose-ranging studies with MRSA strains, the percentage of the dosing interval that the free drug concentration remained higher than the pathogen MIC (fT>MIC) for a 24-h bacteriostatic effect was 5.0% ± 1.4%, and that for a 1-log-unit reduction in count was 12.5% ± 5.8%. Population profiles indicated growth on 2× MIC recovery medium at fT>MIC values of 1 to 35% but not at a value of >35%. In a similar set of experiments with Enterobacteriaceae, the fT>MIC for a 24-h bacteriostatic effect was 34.2% ± 7.6% and that for a 1-log-unit reduction in count was 42.5% ± 7.8%. Population analysis profiles indicated growth on recovery media with 2×, 4×, and 8× MIC at fT>MICs in the range of 1 to 69% but rarely at values of ≥ 70%. In conclusion, razupenem at simulated human doses of 1 g i.v. every 12 h has a marked antibacterial effect on MSSA and MRSA strains with MICs of ≤ 3.0 μg/ml and Enterobacteriaceae with MICs of ≤ 0.4 μg/ml. fT>MIC targets of ≥ 35% for MRSA and ≥ 70% for Enterobacteriaceae should provide significant antibacterial effects combined with low risks of changing pathogen antibiotic population profiles.

The feasibility of a randomised controlled trial of physiotherapy for adults with joint hypermobility syndrome

Abstract: Background Joint hypermobility syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment, but there is little research investigating its clinical effectiveness. Objectives To develop a comprehensive physiotherapy intervention for adults with JHS; to pilot the intervention; and to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. Design Patients’ and health professionals’ perspectives on physiotherapy for JHS were explored in focus groups (stage 1). A working group of patient research partners, clinicians and researchers used this information to develop the physiotherapy intervention. This was piloted and refined on the basis of patients’ and physiotherapists’ feedback (stage 2). A parallel two-arm pilot RCT compared ‘advice’ with ‘advice and physiotherapy’ (stage 3). Random allocation was via an automated randomisation service, devised specifically for the study. Owing to the nature of the interventions, it was not possible to blind clinicians or patients to treatment allocation. Setting Stage 1 – focus groups were conducted in four UK locations. Stages 2 and 3 – piloting of the intervention and the pilot RCT were conducted in two UK secondary care NHS trusts. Participants Stage 1 – patient focus group participants (n = 25, three men) were aged > 18 years, had a JHS diagnosis and had received physiotherapy within the preceding 12 months. The health professional focus group participants (n = 16, three men; 14 physiotherapists, two podiatrists) had experience of managing JHS. Stage 2 – patient participants (n = 8) were aged > 18 years, had a JHS diagnosis and no other musculoskeletal conditions causing pain. Stage 3 – patient participants for the pilot RCT (n = 29) were as for stage 2 but the lower age limit was 16 years. Intervention For the pilot RCT (stage 3) the advice intervention was a one-off session, supplemented by advice booklets. All participants could ask questions specific to their circumstances and receive tailored advice. Participants were randomly allocated to ‘advice’ (no further advice or physiotherapy) or ‘advice and physiotherapy’ (an additional six 30-minute sessions over 4 months). The physiotherapy intervention was supported by a patient handbook and was delivered on a one-to-one patient–therapist basis. It aimed to increase patients’ physical activity through developing knowledge, understanding and skills to better manage their condition. Main outcome measures Data from patient and health professional focus groups formed the main outcome from stage 1. Patient and physiotherapist interview data also formed a major component of stages 2 and 3. The primary outcome in stage 3 related to the feasibility of a future definitive RCT [number of referrals, recruitment and retention rates, and an estimate of the value of information (VOI) of a future RCT]. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events) and resource use (to estimate cost-effectiveness). Outcomes were recorded at baseline, 4 months and 7 months. Results Stage 1 – JHS is complex and unpredictable. Physiotherapists should take a long-term holistic approach rather than treating acutely painful joints in isolation. Stage 2 – a user-informed physiotherapy intervention was developed and evaluated positively. Stage 3 – recruitment to the pilot RCT was challenging, primarily because of a perceived lack of equipoise between advice and physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the advice intervention. Some patients reported that the advice intervention was useful and the physiotherapy intervention was again evaluated very positively. The rate of return of questionnaires was low in the advice group but reasonable in the physiotherapy group. The physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The advice arm experienced more adverse events. The VOI analysis indicated the potential for high value from a future RCT. Such a trial should form the basis of future research efforts. Conclusion A future definitive RCT of physiotherapy for JHS seems feasible, although the advice intervention should be made more robust to address perceived equipoise and subsequent attrition. Trial registration Current Controlled Trials ISRCTN29874209. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 47. See the NIHR Journals Library website for further project information.

Stress, burnout, depression and work satisfaction among UK anaesthetic trainees: a qualitative analysis of in‐depth participant interviews in the Satisfaction and Wellbeing in Anaesthetic Training study

Abstract: Anaesthetists experience unique stressors, and recent evidence suggests a high prevalence of stress and burnout in trainee anaesthetists. There has been no in-depth qualitative analysis to explore this further. We conducted semi-structured interviews to explore contributory and potentially protective factors in the development of perceived stress, burnout, depression and low work satisfaction. We sampled purposively among participants in the Satisfaction and Wellbeing in Anaesthetic Training study, reaching data saturation at 12 interviews. Thematic analysis identified three overarching themes: factors enabling work satisfaction; stressors of being an anaesthetic trainee; and suggestions for improving working conditions. Factors enabling work satisfaction were patient contact; the privilege of enabling good patient outcomes; and strong support at home and work. Stressors were demanding non-clinical work-loads; exhaustion from multiple commitments; a 'love/hate' relationship, as trainees value clinical work but find the training burden immense; feeling 'on edge', even unsafe at work; and the changing way society sees doctors. Nearly all trainees discussed feeling some levels of burnout (which were high and distressing for some) and also high levels of perceived stress. However, trainees also experienced distinct elements of work satisfaction and support. Suggested recommendations for improvement included: allowing contracted hours for non-clinical work; individuals taking responsibility for self-care in and out of work; cultural acceptance that doctors can struggle; and embedding wellbeing support more deeply in organisations and the specialty. Our study provides a foundation for further work to inform organisational and cultural changes, to help translate anaesthetic trainees' passion for their work into a manageable and satisfactory career.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

Abstract: The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial