The NIHR at 10: transforming clinical research

Davies, Sally C.; Walley, Tom; Smye, S W; Cotterill, Lisa Ann; Whitty, Christopher J. M.

doi:10.7861/clinmedicine.16-6-501

Cited by 22 publications

(22 citation statements)

References 6 publications

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“…Multiple mechanisms could favor the deposition of circulating nanoparticles within atherosclerotic plaques. First, it is well accepted that vascular lesions tend to develop at sites characterized by blood flow disturbance and lower shear stresses at the walls . Interestingly, these are also areas where nanoparticle deposition occurs more efficiently due to lower hemodynamic forces, as previously documented by the authors and other investigators .…”

Section: Introductionsupporting

confidence: 64%

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice

Stigliano

Ramirez

Singh

et al. 2017

Adv Healthcare Materials

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Atherosclerosis is an inflammatory disorder characterized by the progressive thickening of blood vessel walls eventually resulting in acute vascular syndromes. Here, intravenously injectable hybrid nanoconstructs are synthesized for tempering immune cell inflammation locally and systemically. Lipid and polymer chains are nanoprecipitated to form 100 nm spherical polymeric nanoconstructs (SPNs), loaded with methotrexate (MTX) and subsequently labeled with Cu and fluorescent probes for combined nuclear/optical imaging. Upon engulfment into macrophages, MTX SPNs intracellularly release their anti-inflammatory cargo significantly lowering the production of proinflammatory cytokine (interleukin 6 and tumor necrosis factor α) already at 0.06 mg mL of MTX. In ApoE mice, fed with high-fat diet up to 17 weeks, nuclear and optical imaging demonstrates specific accumulation of SPNs within lipid-rich plaques along the arterial tree. Histological analyses confirm SPN uptake into macrophages residing within atherosclerotic plaques. A 4-week treatment with biweekly administration of MTX SPNs is sufficient to reduce the plaque burden in ApoE mice by 50%, kept on high-fat diet for 10 weeks. Systemic delivery of MTX to macrophages via multifunctional, hybrid nanoconstructs constitutes an effective strategy to inhibit atherosclerosis progression and induce, potentially, the resorption of vascular lesions.

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Section: Introductionsupporting

confidence: 64%

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice

Stigliano

Ramirez

Singh

et al. 2017

Adv Healthcare Materials

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“…Similarly, the chief medical officer argues that ‘developing the next generation of research leaders in clinical research is essential to the UK, (Davies, 502)24 but the data suggest a cliff-edge in the pathway; greater numbers of practitioners are embarking on clinical academic careers, but following PhD, opportunities are scarce. The fortunate have the organisational backing to ‘trailblaze’, but others face a decision to return to their pre-PhD clinical role (and hence not have their academic skills recognised and utilised) or follow a traditional academic research pathway and leave their clinical post behind (thus negating the whole reason for pursuing a clinical academic career).…”

Section: Resultsmentioning

confidence: 99%

A mixed-methods study of challenges and benefits of clinical academic careers for nurses, midwives and allied health professionals

2019

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ObjectivesThe clinical academic trajectory for doctors and dentists is well-established, with research embedded in their career development. Recent years have also seen a burgeoning interest and push for nurses, midwives and allied health professionals (NMAHPs) to pursue a clinical academic career. However, the National Institute for Health Research (NIHR) 10-year review suggested that there may be problems with progression post Master’s degree level for this group, with nurses and midwives receiving less NIHR funding than allied health professionals. This study responds to these concerns, tracking the progression and exploring experiences of NMAHPs in the East Midlands region of England.DesignAn online survey and in-depth interviews were used to capture a wide range of experiences.Participants67 NMAHPs who were pursuing a clinical academic career were surveyed, supplemented by 16 semi-structured in-depth interviews.ResultsThree themes emerged during data analysis: Embarking on a clinical academic career, overcoming barriers and benefits.ConclusionsNMAHPs are motivated to pursue a clinical academic career by a drive to improve services for the benefit of patients and the National Health Service more widely, as well as for personal development and career progression. People working in these roles have opportunities to explore possible solutions to issues that they encounter in their clinical role through academic study. Findings reveal benefits emanating from the individual level through to (inter)national levels, therefore academic study should be encouraged and supported. However, investment is needed to establish more clinical academic roles to enable NMAHPs to continue to use their experience and expertise post-PhD, otherwise the full extent of their value will not be recognised.

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“…England is unique in having a national research infrastructure (the NIHR Clinical Research Network) that provides national coverage in opportunities for research participation [11,12]. The network comprises 15 Local Clinical Research Networks (LCRNs) covering England.…”

Section: Introductionmentioning

confidence: 99%

Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

Bower

Grigoroglou

Anselmi

et al. 2020

BMC Med

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Background: Research is fundamental to high-quality care, but concerns have been raised about whether health research is conducted in the populations most affected by high disease prevalence. Geographical distribution of research activity is important for many reasons. Recruitment is a major barrier to research delivery, and undertaking recruitment in areas of high prevalence could be more efficient. Regional variability exists in risk factors and outcomes, so research done in healthier populations may not generalise. Much applied health research evaluates interventions, and their impact may vary by context (including geography). Finally, fairness dictates that publically funded research should be accessible to all, so that benefits of participating can be fairly distributed. We explored whether recruitment of patients to health research is aligned with disease prevalence in England. Methods: We measured disease prevalence using the Quality and Outcomes Framework in England (total longterm conditions, mental health and diabetes). We measured research activity using data from the NIHR Clinical Research Network. We presented descriptive data on geographical variation in recruitment rates. We explored associations between the recruitment rate and disease prevalence rate. We calculated the share of patient recruitment that would need to be redistributed to align recruitment with prevalence. We assessed whether associations between recruitment rate and disease prevalence varied between conditions, and over time. Results: There was significant geographical variation in recruitment rates. When areas were ranked by disease prevalence, recruitment was not aligned with prevalence, with disproportionately low recruitment in areas with higher prevalence of total long-term and mental health conditions. At the level of 15 local networks, analyses suggested that around 12% of current recruitment activity would need to be redistributed to align with disease prevalence. Overall, alignment showed little change over time, but there was variation in the trends over time in individual conditions.

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The NIHR at 10: transforming clinical research

Cited by 22 publications

References 6 publications

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice

A mixed-methods study of challenges and benefits of clinical academic careers for nurses, midwives and allied health professionals

Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

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The NIHR at 10: transforming clinical research

Cited by 22 publications

References 6 publications

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice

A mixed-methods study of challenges and benefits of clinical academic careers for nurses, midwives and allied health professionals

Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

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Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE^−/− Mice