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Biomedical subjects

David Russell

Publications and source records attributed to David Russell.

At least 19 recordsLinked to original sources

Development of a core descriptor set for studies assessing interventions for diabetes-related foot ulceration.

AIMS/HYPOTHESIS: Foot ulceration is a common complication of diabetes and is associated with high mortality and costs. The quality of evidence to inform clinical practice is limited, partly because clinical studies do not consistently report baseline participant characteristics. This study aimed to develop a core descriptor set (CDS), a minimum set of descriptors to be measured in all studies evaluating interventions for people with diabetes-related foot ulceration. METHODS: A longlist of descriptors was generated through a systematic review of studies assessing interventions for diabetes-related foot ulcers, pre-registered with PROSPERO (CRD42019128250). The identified descriptors were then ranked based on perceived importance by healthcare professionals from different fields and geographical locations using a nine-point Likert scale in the first round of a Delphi survey. Using standardised criteria, descriptors without consensus were re-ranked in round two. Critical descriptors and those without consensus after the Delphi process were discussed in the consensus meeting to finalise the CDS. RESULTS: The systematic review yielded 95 candidate descriptors. The two Delphi rounds were completed by 102 and 69 healthcare professionals, respectively. The Delphi process identified 34 critically important descriptors and 13 descriptors without consensus, which were discussed in the consensus meeting. The ratified CDS included 28 descriptors across nine domains: demographic variables; individual factors; ulcer characteristics; limb characteristics; ongoing medical interventions; previous surgical interventions; medication history; biochemical measurements; and quality of life/function/symptoms. CONCLUSIONS/INTERPRETATION: This CDS reflects characteristics important to health professionals and researchers when reporting clinical studies on diabetes-related foot ulceration. Its use will aid the reporting of future studies.

Humans↗

The effect of patient self-completion agenda forms on prescribing and adherence in general practice: a randomized controlled trial.

BACKGROUND: What the patient wants from a general practice consultation and what the doctor believes they want are not always the same thing. This mismatch may lead to unwanted and unnecessary prescribing. AIM: To study the effect of a one-page form completed by patients before their consultation and given to the doctor at the start of the consultation, in terms of a reduction in prescribing, satisfaction with the consultation and adherence with prescribed medication. DESIGN: Randomized controlled trial. SETTING: Ten general practices in Devon and Dorset, UK. METHODS: Unselected patients attending general practice appointments were randomised to receive (or not) a self-completed agenda form (SCAF) asking five questions, including whether the patient considered they should receive a prescription. RESULTS: Approximately 4125 patients were offered entry; 3124 (76%) agreed to randomisation. In 1783 (57%) of these prescribing or satisfaction outcomes were identified. 457 of 811 (56.4%) of SCAF patients received a prescription, at a median (IQR) cost of pound 5.60 (inter-quartile range pound 2.12- pound 16.10), compared with 418 of 799 (52.3%) of controls, at a median cost of pound 5.94 ( pound 2.46- pound 18.90); both results non-significant (P=0.10 for prescribing and 0.30 for cost). Satisfaction was also similar in both groups: mean satisfaction score in SCAFs 5.37 and in controls 5.40 (P=0.64), as was adherence: at 12 weeks, adherence of 75% or greater was reported by 92 of 136 SCAF patients (68%) and 105 of 145 controls (72%) (P=0.31). CONCLUSION: The negative result could have two explanations. Either the intervention did not achieve the intention of communicating the patients' agendas, or if it did, patients may have been persuaded by doctors' explanations in the consultation.

Adult↗

Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors.

The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs). Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide dismutase 1; G59S p150(glued)) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.

Adenosine A2 Receptor Antagonists↗

Hippocampus function predicts severity of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is often accompanied by memory problems and abnormal brain structure, particularly within the hippocampus. We implemented a cross-species, hippocampal-dependent task--the virtual Morris Water task--to assess hippocampal function in people with PTSD and age-matched controls during functional magnetic resonance imaging (fMRI). Performance on the task was equivalent between the groups. However, when correlating fMRI-derived hippocampal activity during this task with PTSD severity, we observe a -0.84 correlation, indicating that those with reduced hippocampal activity show more severe PTSD symptoms. This correlation is not explained by differences in task performance, IQ, duration since trauma, nor time with PTSD. Hence, PTSD severity is predicted by functionally assessing the hippocampus using the virtual Morris water task, suggesting that this task may be used to identify those at risk for developing PTSD following a trauma.

Brain Mapping↗

The economic effect of switching from sildenafil to another phosphodiesterase type 5 inhibitor.

Patients who could benefit from additional education about treatments for erectile dysfunction (ED) may prematurely discontinue or switch ED medications, resulting in unnecessary resource utilization. In a retrospective cohort study using a large, aggregated health claims database, the costs associated with switching from sildenafil to another phosphodiesterase type 5 (PDE-5) inhibitor were compared with those for patients refilling sildenafil. Of the 15,584 patients with an index sildenafil claim, 10,863 had a second PDE-5 inhibitor prescription (10,137 for sildenafil, 726 for vardenafil or tadalafil). Erectile dysfunction-attributable costs in the six-month preindex period were similar (P = .72), but postindex six-month ED costs were higher in patients who initially switched from sildenafil (dollar 173.38) versus patients who refilled sildenafil (dollar 131.51; P < .001). Regression analysis estimated that corrected ED-attributable and overall costs were 41% (P < .001) and 43% (P < .001) higher for patients who switched versus those who refilled sildenafil, respectively.

Aged↗

Combined carotid and transcranial ultrasound findings compared with clinical classification and stroke severity in acute ischemic stroke.

BACKGROUND: The aim of this study was to assess the association between cerebral hemodynamics and the clinical picture as defined by the Oxfordshire Community Stroke Project (OCSP) classification, as well as the clinical severity as defined by the National Institute of Health Stroke Scale (NIHSS) within the first 6 h of an acute middle cerebral artery (MCA) stroke onset. METHODS: 70 unselected patients were grouped according to the OCSP classification and NIHSS. All patients immediately had extracranial and transcranial Doppler (TCD) ultrasound examinations. RESULTS: In the study population as a whole, there was a significant association between intracranial vascular pathology and the OCSP classification (p<0.001) as well as the NIHSS score (p<0.001). In patients with severe stroke, however, TCD demonstrated the hypothesized proximal MCA(1) occlusion in only 34% of patients with an OCSP-defined total anterior circulation syndrome and in 42% of patients with an NIHSS score of >or=15. In moderate stroke, the OCSP classification was misleading in almost half of the patients with a partial anterior circulation syndrome, i.e. a hypothesized distal MCA(2) occlusion suitable for thrombolysis. CONCLUSIONS: Neither the OCSP classification nor the NIHSS grading provided reliable information about the site or presence of intracranial arterial occlusion in acute stroke within the first 6 h after stroke onset in the individual patient. The results of this study strongly suggest that selection of acute ischemic stroke patients for thrombolysis should also include an assessment of cerebral hemodynamics.

Adolescent↗

Long-term effect of intravenous thrombolytic therapy in acute stroke: responder analysis versus uniform analysis of excellent outcome.

BACKGROUND: Knowledge regarding functional improvement over time and long-term outcome after intravenous thrombolysis in acute ischaemic stroke is limited. The aim of this study was to compare a uniform assessment of outcome with an assessment taking the baseline stroke severity into account (responder analysis). METHODS: Fifty-seven patients were assessed with the modified Rankin Scale at 3, 6 and 12 months and a comparison was made between a uniform assessment and a responder analysis of excellent outcome. RESULTS: Between 3 and 12 months, 74% of the patients had a stable functional outcome and 22% improved. Excellent outcome at 12 months was similar in the uniform analysis (37%) and the responder analysis (35%). The individual patients having an excellent outcome differed, however, using the two methods. Using a responder analysis the number of patients with excellent outcome decreased in mild stroke patients by 40%, but increased in severe stroke patients by 43%. CONCLUSIONS: Short-term outcome is sustained at 12 months, but major improvement does not occur between 3 and 12 months. A responder analysis of long-term excellent outcome provided a balanced measure of outcome reflecting the drug-related potential of improvement in all stroke severity subgroups, whereas a uniform analysis provided a measure of outcome mainly in mild stroke patients. These results suggest that a responder analysis should be considered for the assessment of outcome after treatment for acute stroke.

Adolescent↗

A dark jet dominates the power output of the stellar black hole Cygnus X-1.

Black holes undergoing accretion are thought to emit the bulk of their power in the X-ray band by releasing the gravitational potential energy of the infalling matter. At the same time, they are capable of producing highly collimated jets of energy and particles flowing out of the system with relativistic velocities. Here we show that the 10-solar-mass (10M(o)) black hole in the X-ray binary Cygnus X-1 (refs 3-5) is surrounded by a large-scale (approximately 5 pc in diameter) ring-like structure that appears to be inflated by the inner radio jet. We estimate that in order to sustain the observed emission of the ring, the jet of Cygnus X-1 has to carry a kinetic power that can be as high as the bolometric X-ray luminosity of the binary system. This result may imply that low-luminosity stellar-mass black holes as a whole dissipate the bulk of the liberated accretion power in the form of 'dark', radiatively inefficient relativistic outflows, rather than locally in the X-ray-emitting inflow.

Journal Article↗

[Can ischaemic stroke be prevented with statins?].

BACKGROUND: Statins provide a reduction in the risk for ischaemic stroke in patients with coronary artery disease, known atherosclerotic disease, and in patients with risk factors for arterial vascular disease. There is also considerable interest in whether or not statins should be used as a secondary prophylaxis for stroke. MATERIALS AND METHOD: This review is based on articles included on Medline that consider the association between cholesterol and cerebrovascular disease and the use of statins in ischaemic stroke. RESULTS: Cholesterol is a much weaker risk factor for ischaemic stroke than for coronary heart disease. It is especially associated with thromboembolic stroke due to atherosclerosis of the larger vessels. Meta-analysis of earlier studies in patients with coronary artery disease and several more recent studies which include patients with other atherosclerotic disease and risk factors for atherosclerosis have clearly shown a relative risk reduction for ischaemic stroke of between 20 and 30%. Since these studies were of patients in age groups in which stroke rarely occurs, the relative risk reduction was moderate. Risk reduction seems similar in all age groups with atherosclerotic heart disease and for all cholesterol levels. A reduced risk for a new stroke has to date not been shown for patients with previous stroke. CONCLUSION: Given the fact that stroke is caused by several mechanisms and is often not caused by atherosclerosis of larger vessels, definite advice cannot be given on secondary prevention with statins in all stroke patients. At present there are no results from studies where only ischaemic stroke patients were included and with a sufficient number of older patients.

Aged↗

Cerebral emboli during left heart catheterization may cause acute brain injury.

AIMS: Left heart catheterization carries a risk for cerebral complications. The aims of this prospective study were to determine the frequency and composition of catheterization-related cerebral microemboli and to detect cerebral morphological changes and acute cognitive impairment due to catheterization. METHODS AND RESULTS: Forty-seven unselected patients undergoing elective left heart catheterization, either by transradial or by transfemoral access, were monitored for cerebral microemboli using multifrequency transcranial Doppler. Cerebral magnetic resonance imaging (MRI) with diffusion-weighted imaging sequences and neuropsychological assessments were carried out on the day before and the day after catheterization. A median number of 754 cerebral microemboli were detected: 92.1% were gaseous and 7.9% were solid. New cerebral lesions were observed in 15.2% of the transradial, but none of the transfemoral, catheterization patients (P=0.567). These lesions were significantly associated with a higher number of solid microemboli (P=0.016) and a longer fluoroscopy time (P=0.039). There was also a significantly higher number of solid microemboli during transradial than during transfemoral catheterization (P=0.012). Cognitive impairment following the investigations was associated with the degree of pre-catheterization cerebral MRI injury (P=0.03). CONCLUSION: During left heart catheterization, cerebral microemboli, especially those which are solid, may damage the brain. Cardiac catheterization may therefore pose a greater risk for the brain than previously acknowledged.

Aged↗

What did William Hunter know about bone?

This article examines William Hunter's specimens on bone in the Anatomy Museum at the University of Glasgow. By referring to students' notes taken at Hunter's lectures and to the Manuscript Catalogue of his anatomical specimens, we attempt to answer the question, "What did William Hunter know about bone?" Hunter seems to have been particularly interested in the relationship between vascularisation and ossification and many of the specimens illustrate this. He provided his students with reasoned arguments on a number of issues: that the marrow serves as a fat store and not to produce synovial fluid or to keep bones supple; the periosteum serves as an attachment for tendons and ligaments; the rationale for the presence of epiphyses is not readily defined; that bones form by intramembranous and endochondral ossification and that, in the latter, cartilage is replaced by bone. William Hunter narrowly failed to realise that in long bones new bone is laid down by the periosteum and at the epiphysial plates, and is remodeled. These discoveries were to be made by his brother, John.

Anatomy↗

Cerebral ischemic injury and cognitive impairment after off-pump and on-pump coronary artery bypass grafting surgery.

BACKGROUND: Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury. The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment. We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery. METHODS: One hundred twenty patients with ischemic coronary artery disease were prospectively randomized to undergo off-pump or on-pump surgery. A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively. The neuropsychological assessment was repeated at 12 months. RESULTS: There was no significant (p = 0.17) difference between off-pump (8.2%) and on-pump (17.3%) surgery with regard to new postoperative cerebral lesions. The prevalence of cognitive impairment after surgery was also similar in the two groups (3 months: off-pump 20.4%, on-pump 23.1%, p = 0.74; 12 months: off-pump 24.1%, on-pump 23.1%, p = 0.90). The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump (p = 0.02) but not after off-pump (p = 0.22) surgery. None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively (p = 0.04). CONCLUSIONS: Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery. Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery.

Adult↗

Preoperative cerebral ischemic lesions predict physical health status after on-pump coronary artery bypass surgery.

BACKGROUND: Risk assessment is integral to patient selection and counseling before coronary artery revascularization. We studied the predictive ability of cerebral magnetic resonance imaging of preoperative and postoperative cerebral ischemic injury on self-reported physical and mental health at 3 months after coronary artery bypass surgery with or without use of cardiopulmonary bypass. METHODS: In a prospective clinical trial comparing on-pump and off-pump surgery, 120 patients responded to a questionnaire for self-report of angina (Canadian Cardiovascular Society scale) and physical and mental health status (Short Form 36) at baseline before preoperative cerebral magnetic resonance imaging. Preoperative sets of both magnetic resonance imaging and self-assessments were available for 103 (85.8%) patients. These patients were grouped according to classification of preoperative cerebral magnetic resonance imaging findings. Analysis of covariance determined the association of (1) preoperative magnetic resonance imaging status, (2) new postoperative cerebral lesions, and (3) actual use of cardiopulmonary bypass to physical and mental health. RESULTS: At 3 months after surgical intervention, 98 of 103 patients completed follow-up. The analysis revealed an interaction effect of preoperative cerebral ischemic injury and use of cardiopulmonary bypass on physical health (F = 9.07, P = .003) independent of age. No independent effects on health status were found of baseline magnetic resonance imaging or new cerebral lesions at 3 months. CONCLUSIONS: This study strongly suggests that the combination of preoperative cerebral ischemic injury and use of cardiopulmonary bypass can predict postoperative health status at 3 months. Cerebral magnetic resonance imaging might be a more specific indicator than age for preoperative assessment of vulnerability or resilience during rehabilitation after on-pump cardiac surgery.

Adult↗