Mary Joan Macleod

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke.

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10−11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

Stress, debt and undergraduate medical student performance.

Introduction  Against the background of current debate over university funding and widening access, we aimed to examine the relationships between student debt, mental health and academic performance.

Increased sensitivity after repeated stimulation of residual spatial channels in blindsight

Lesions of the occipital cortex result in areas of cortical blindness affecting the corresponding regions of the patients visual field. The traditional view is that, aside from some spontaneous recovery in the first few months after the damage, when acute effects have subsided the areas of blindness are absolute and permanent. It has been found, however, that within such field defects some residual visual capacities may persist in the absence of acknowledged awareness by the subject (blindsight type 1) or impaired awareness (type 2). Neuronal pathways mediating blindsight have a specific and narrow spatial and temporal bandwidth. A group of cortically blind patients (n = 12) carried out a daily detection “training” task over a 3-month period, discriminating grating visual stimuli optimally configured for blindsight from homogeneous luminance-matched stimuli. No feedback was given during the training. Assessment of training was by psychophysical measurements carried out before and after training and included detection of a range of spatial frequencies (0.5–7 cycles per degree), contrast detection at 1 cycle per degree, clinical perimetry, and subjective estimates of visual field defect. The results show that repeated stimulation by appropriate visual stimuli can result in improvements in visual sensitivities in the very depths of the field defect.

What is the scale of prescribing errors committed by junior doctors? A systematic review

AIMS Prescribing errors are an important cause of patient safety incidents, generally considered to be made more frequently by junior doctors, but prevalence and causality are unclear. In order to inform the design of an educational intervention, a systematic review of the literature on prescribing errors made by junior doctors was undertaken. METHODS Searches were undertaken using the following databases: MEDLINE; EMBASE; Science and Social Sciences Citation Index; CINAHL; Health Management Information Consortium; PsychINFO; ISI Proceedings; The Proceedings of the British Pharmacological Society; Cochrane Library; National Research Register; Current Controlled Trials; and Index to Theses. Studies were selected if they reported prescribing errors committed by junior doctors in primary or secondary care, were in English, published since 1990 and undertaken in Western Europe, North America or Australasia. RESULTS Twenty-four studies meeting the inclusion criteria were identified. The range of error rates was 2-514 per 1000 items prescribed and 4.2-82% of patients or charts reviewed. Considerable variation was seen in design, methods, error definitions and error rates reported. CONCLUSIONS The review reveals a widespread problem that does not appear to be associated with different training models, healthcare systems or infrastructure. There was a range of designs, methods, error definitions and error rates, making meaningful conclusions difficult. No definitive study of prescribing errors has yet been conducted, and is urgently needed to provide reliable baseline data for interventions aimed at reducing errors. It is vital that future research is well constructed and generalizable using standard definitions and methods.

Perceived causes of prescribing errors by junior doctors in hospital inpatients: a study from the PROTECT programme

Introduction Prescribing errors are a major cause of patient safety incidents. Understanding the underlying factors is essential in developing interventions to address this problem. This study aimed to investigate the perceived causes of prescribing errors among foundation (junior) doctors in Scotland. Methods In eight Scottish hospitals, data on prescribing errors were collected by ward pharmacists over a 14-month period. Foundation doctors responsible for making a prescribing error were interviewed about the perceived causes. Interview transcripts were analysed using content analysis and categorised into themes previously identified under Reasons Model of Accident Causation and Human Error. Results 40 prescribers were interviewed about 100 specific errors. Multiple perceived causes for all types of error were identified and were categorised into five categories of error-producing conditions, (environment, team, individual, task and patient factors). Work environment was identified as an important aspect by all doctors, especially workload and time pressures. Team factors included multiple individuals and teams involved with a patient, poor communication, poor medicines reconciliation and documentation and following incorrect instructions from other members of the team. A further team factor was the assumption that another member of the team would identify any errors made. The most frequently noted individual factors were lack of personal knowledge and experience. The main task factor identified was poor availability of drug information at admission and the most frequently stated patient factor was complexity. Conclusions This study has emphasised the complex nature of prescribing errors, and the wide range of error-producing conditions within hospitals including the work environment, team, task, individual and patient. Further work is now needed to develop and assess interventions that address these possible causes in order to reduce prescribing error rates.

Spatial channels of visual processing in cortical blindness

Blindsight is the ability of some cortically blind patients to discriminate visual events presented within their field defect. We have examined a fundamental aspect of visual processing, namely the detection of spatial structures presented within the field defect of 10 cortically blind patients. The method outlined is based on the detection of high‐contrast stimuli and is effective in flagging a ‘window of detection’ in the spatial frequency spectrum, should it exist. Here we report on the presence of a narrowly tuned psychophysical spatial channel optimally responding to frequencies less than 4 cycles/° in eight out of 10 patients tested. The two patients who did not show any evidence of blindsight appear to have intact midbrain structures, but have lesions that extend from the occipital cortex to the thalamus. In addition, we have recorded subjective reports of awareness of the visual events in each trial. Detection scores of eight blindsight patients were subsequently subdivided based on the subjective reports of awareness. It appears that the psychophysical spatial channel‐mediating responses in the absence of any awareness of the visual event have a narrower frequency response than those involved when the patients report some awareness of the visual event. The findings are discussed in relation to previous reports on the incidence of blindsight and performance on tasks involving spatial processing.

Stroke patients admitted within normal working hours are more likely to achieve process standards and to have better outcomes

Background The presence of a ‘weekend’ effect has been shown across a range of medical conditions, but has not been consistently observed for patients with stroke. Aims We investigated the impact of admission time on a range of process and outcome measures after stroke. Methods Using routine data from National Scottish data sets (2005–2013), time of admission was categorised into weekday, weeknight and weekend/public holidays. The main process measures were swallow screen on day of admission (day 0), brain scan (day 0 or 1), aspirin (day 0 or 1), admission to stroke unit (day 0 or 1), and thrombolysis administration. After case-mix adjustment, multivariable logistic regression was used to estimate the OR for mortality and discharge to home/usual place of residence. Results There were 52 276 index stroke events. Compared to weekday, the adjusted OR (95%CI) for early stroke unit admission was 0.81 (0.77 to 0.85) for weeknight admissions and 0.64 (0.61 to 0.67) for weekend/holiday admissions; early brain scan 1.30 (0.87 to 1.94) and 1.43 (0.95 to 2.18); same day swallow screen 0.86 (0.81 to 0.91) and 0.85 (0.81 to 0.90); thrombolysis 0.85 (0.75 to 0.97) and 0.85 (0.75 to 0.97), respectively. Seven-day mortality, 30-day mortality and 30-day discharge for weekend admission compared to weekday was 1.17 (1.05 to 1.30); 1.08 (1.00 to 1.17); and 0.90 (0.85 to 0.95), respectively. Conclusions Patients with stroke admitted out of hours and at weekends or public holidays are less likely to be managed according to current guidelines. They experience poorer short-term outcomes than those admitted during normal working hours, after correcting for known independent predictors of outcome and early mortality.

Implementing a Simple Care Bundle Is Associated With Improved Outcomes in a National Cohort of Patients With Ischemic Stroke

Background and Purpose— Further research is needed to better identify the methods of evaluating processes and outcomes of stroke care. We investigated whether achieving 4 evidence-based components of a care bundle in a Scotland-wide population with ischemic stroke is associated with 30-day and 6-month outcomes. Methods— Using national datasets, we looked at the effect of 4 standards (stroke unit entry on calendar day of admission [day 0] or day following [day 1], aspirin on day 0 or day 1, scan on day 0, and swallow screen recorded on day 0) on mortality and discharge to usual residence, at 30 days and 6 months. Data were corrected for the validated 6 simple variables, admission year, and hospital-level random effects. Results— A total of 36 055 patients were included. Achieving stroke unit admission, swallow screen, and aspirin standards were associated with reduced 30-day mortality (adjusted odds ratio [95% confidence interval]: 0.82 [0.75–0.90], 0.88 [0.77–0.99], and 0.39 [0.35–0.43], respectively). Thirty-day all-cause mortality was higher when fewer standards were achieved, from 0 versus 4 (adjusted odds ratio [95% confidence interval], 2.95 [1.91–4.55]) to 3 versus 4 (adjusted odds ratio [95% confidence interval], 1.21 [1.09–1.34]). This effect persisted at 6 months. When less than the full care bundle was achieved, discharge to usual residence was less likely at 6 months (3 versus 4 standards; adjusted odds ratio [95% confidence interval], 0.91 [0.85–0.98]). Conclusions— Achieving a care bundle for ischemic stroke is associated with reduced mortality at 30 days and 6 months and increased likelihood of discharge to usual residence at 6 months.

Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study

Background In randomised trials testing treatments for acute ischaemic stroke, imaging markers of tissue reperfusion and arterial recanalisation may provide early response indicators. Objective To determine the predictive value of structural, perfusion and angiographic imaging for early and late clinical outcomes and assess practicalities in three comprehensive stroke centres. Methods We recruited patients with potentially disabling stroke in three stroke centres, performed magnetic resonance (MR) or CT, including perfusion and angiography imaging, within 6 h, at 72 h and 1 month after stroke. We assessed the National Institutes of Health Stroke Scale (NIHSS) score serially and functional outcome at 3 months, tested associations between clinical variables and structural imaging, several perfusion parameters and angiography. Results Among 83 patients, median age 71 (maximum 89), median NIHSS 7 (range 1–30), 38 (46%) received alteplase, 41 (49%) had died or were dependent at 3 months. Most baseline imaging was CT (76%); follow-up was MR (79%) despite both being available acutely. At presentation, perfusion lesion size varied considerably between parameters (p<0.0001); 40 (48%) had arterial occlusion. Arterial occlusion and baseline perfusion lesion extent were both associated with baseline NIHSS (p<0.0001). Recanalisation by 72 h was associated with 1 month NIHSS (p=0.0007) and 3 month functional outcome (p=0.048), whereas tissue reperfusion, using even the best perfusion parameter, was not (p=0.11, p=0.08, respectively). Conclusion Early recanalisation on angiography appeared to predict clinical outcome more directly than did tissue reperfusion. Acute assessment with CT and follow-up with MR was practical and feasible, did not preclude image analysis, and would enhance trial recruitment and generalisability of results.

HÆMODIALYSIS THERAPY AND CHANGES IN SKELETAL CALCIUM

Abstract Neutron-activation analysis of a hand, photon absorption by a radius, and skeletal radiography were used to assess changes in the mineral content of bone over a period of 26 weeks in thirteen patients on regular haemodialysis. Radiological change was noted in 15% of the patients studied, and there was evidence of demineralisation in 77% by photon absorption and in 93% by neutron activation. The mean calcium loss measured by neutron activation (10·8%) was considerably greater than the mean decrease in total bone mineral assessed by photon absorption (3·8%). It is suggested that neutron-activation analysis of a hand is a sensitive indicator of the rate of progression, or improvement, in metabolic bone disease.