Age at menarche and adult body mass index: a Mendelian randomization study.

BACKGROUND: Pubertal timing has psychological and physical sequelae. While observational studies have demonstrated an association between age at menarche and adult body mass index (BMI), confounding makes it difficult to infer causality. METHODS: The Mendelian randomization (MR) technique is not limited by traditional confounding and was used to investigate the presence of a causal effect of age at menarche on adult BMI. MR uses genetic variants as instruments under the assumption that they act on BMI only through age at menarche (no pleiotropy). Using a two-sample MR approach, heterogeneity between the MR estimates from individual instruments was used as a proxy for pleiotropy, with sensitivity analyses performed if detected. Genetic instruments and estimates of their association with age at menarche were obtained from a genome-wide association meta-analysis on 182,416 women. The genetic effects on adult BMI were estimated using data on 80,465 women from the UK Biobank. The presence of a causal effect of age at menarche on adult BMI was further investigated using data on 70,692 women from the GIANT Consortium. RESULTS: There was evidence of pleiotropy among instruments. Using the UK Biobank data, after removing instruments associated with childhood BMI that were likely exerting pleiotropy, fixed-effect meta-analysis across instruments demonstrated that a 1 year increase in age at menarche reduces adult BMI by 0.38 kg/m2 (95% CI 0.25-0.51 kg/m2). However, evidence of pleiotropy remained. MR-Egger regression did not suggest directional bias, and similar estimates to the fixed-effect meta-analysis were obtained in sensitivity analyses when using a random-effect model, multivariable MR, MR-Egger regression, a weighted median estimator and a weighted mode-based estimator. The direction and significance of the causal effect were replicated using GIANT Consortium data. CONCLUSION: MR provides evidence to support the hypothesis that earlier age at menarche causes higher adult BMI. Complex hormonal and psychological factors may be responsible.

Development of a web-based tool for undergraduate engagement in medical research; the ProjectPal experience.

BACKGROUND: We report the development and evaluation of a web-based tool designed to facilitate student extra-curricular engagement in medical research through project matching students with academic supervisors. UK based university students were surveyed to explore their perceptions of undergraduate research, barriers and facilitators to current engagement. Following this, an online web-based intervention ( www.ProjectPal.org ) was developed to support access of students to research projects and supervisors. A pilot intervention was undertaken across a London-based university in January 2013 to February 2016. In March 2016, anonymised data were extracted from the prospective data log for analysis of website engagement and usage. Supervisors were surveyed to evaluate the website and student outputs. RESULTS: Fifty-one students responded to the electronic survey. Twenty-four (47%) reported frustration at a perceived lack of opportunities to carry out extra-curricular academic projects. Major barriers to engaging in undergraduate research reported were difficulties in identifying suitable supervisors (33/51; 65%) and time pressures (36/51; 71%) associated with this. Students reported being opportunistic in their engagement with undergraduate research. Following implementation of the website, 438 students signed up to ProjectPal and the website was accessed 1357 times. Access increased on a yearly basis. Overall, 70 projects were advertised by 35 supervisors. There were 86 applications made by students for these projects. By February 2016, the 70 projects had generated 5 peer-review publications with a further 7 manuscripts under peer-review, 14 national presentations, and 1 national prize. CONCLUSION: The use of an online platform to promote undergraduate engagement with extra-curricular research appears to facilitate extra-curricular engagement with research. Further work to understand the impact compared to normal opportunistic practices in enhancing student engagement is now underway.

Temporal Trends in the Levels of Peripherally Circulating Leukocyte Subtypes in the Hours after Ischemic Stroke.

BACKGROUND: Leukocyte-mediated neuroinflammation may affect outcomes after ischemic stroke. AIMS: To explore temporal changes in levels of peripherally circulating leukocyte subtypes in the early hours after ischemic stroke in humans. METHODS: Retrospective analysis of a single-center database of consecutive thrombolysis cases for acute ischemic stroke (AIS). Multivariable regression analysis was used to explore temporal changes in the levels of peripherally circulating leukocyte subtypes in the hours immediately after ischemic stroke. A natural logarithm transformation was used to achieve normally distributed residuals, and adjustment was made for the severity of stroke, blood glucose concentration, sex, and age. RESULTS: Blood samples were taken a median time of approximately 2 hours after stroke symptom onset. Median peripheral neutrophil and lymphocyte counts on admission were 4.8 × 109cells per liter (interquartile range [IQR], 3.6-7.2 × 109 cells per liter) and 1.9 × 109cells per liter (IQR, 1.3-2.6 × 109cells per liter), respectively. Multivariable regression analysis revealed that after adjustment there was a linear increase in the natural logarithm of the peripheral neutrophil count (P < .01), with a linear decrease in the natural logarithm of the peripheral lymphocyte count (P < .01) in the hours immediately after stroke onset. No significant temporal associations were found between the levels of the other peripherally circulating leukocyte subtypes. CONCLUSIONS: Immediately after ischemic stroke, there is an exponential increase in the neutrophil count and an exponential decrease in the lymphocyte count.

A Retrospective Cohort Study on the Use of Intravenous Thrombolysis in Stroke Mimics.

BACKGROUND: The urgency of intravenous thrombolysis in acute ischemic stroke can lead to inadvertent thrombolysis of patients with nonstroke diagnoses (stroke mimics), increasing the risk of adverse events. The objectives of this study were to compare thrombolysed acute ischemic stroke and stroke mimic cases based on demographic factors, physiological parameters, radiological findings, and clinical presentation, and to evaluate the clinical implications of thrombolysing stroke mimics. METHODS: A retrospective analysis of a single-center database of all thrombolysed strokes and mimics over a period greater than 3 years. Diagnoses were confirmed by expert consensus after a review of clinical factors and imaging. Intercohort variation was assessed using Wilcoxon rank-sum or Pearson's chi-square test. RESULTS: The stroke mimic cohort tended to be younger (mean age 59.9 years versus 73.7 years, P < .001) and had a lower National Institutes of Health Stroke Score at presentation (mean 5.9 points versus 6.4 points, P < .01). However, the time taken from the onset of symptoms to delivery of thrombolytic drugs was longer in the mimic cohort (mean time 170 minutes versus 138 minutes, P < .01). Any differences in blood glucose (P = .07), time taken from hospital arrival to delivery of intravenous thrombolysis (P = .57), and blood pressure on admission (systolic, P = .09 and diastolic, P = .34) were not statistically significant. No adverse events were reported in the mimic cohort. CONCLUSION: Despite similarities in clinical presentation, thrombolysed stroke mimics are of a different physiological and demographic population, and are associated with fewer adverse events compared with thrombolysed acute ischemic stroke patients.

Trends in C-Reactive Protein Levels Are Associated with Neurological Change Twenty-Four Hours after Thrombolysis for Acute Ischemic Stroke.

BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) are associated with worse outcomes in patients thrombolysed for acute ischemic stroke (AIS). AIMS: To investigate whether changes in CRP levels are associated with neurological change after thrombolysis for AIS. METHODS: Retrospective analysis of a single-center database of consecutive thrombolysis cases for AIS from October 18, 2011, to June 15, 2015, inclusive. Multivariate regression analysis was used to investigate the relationship between change in CRP 12-24 hours after thrombolysis and change in NIHSS (National Institutes of Health Stroke Scale) score 24 hours after thrombolysis. The other potentially confounding predictor variables included in the model were CRP on admission and NIHSS score before thrombolysis. RESULTS: Complete data were available for 108 out of possible 435 eligible patients. Increases in CRP levels 12-24 hours after thrombolysis were negatively associated with reduction in NIHSS score 24 hours after thrombolysis (coefficient .08, 95% confidence interval .031-.129, P = .002). Thus, on average, for every 12.5 mg/L additional increase in CRP 12-24 hours after thrombolysis, NIHSS score at 24 hours improved by 1 point less. CONCLUSION: While it was previously known that elevated CRP levels are associated with worse outcomes in patients thrombolysed for AIS, the current work demonstrates that changes in CRP levels after thrombolysis also relate to neurological change, and thus may have scope for use as prognostic markers.

Clinician-directed improvement in the accuracy of hospital clinical coding.

'Payment by results' (PbR) remuneration for healthcare services relies on the accurate conversion of diagnoses into Healthcare Resource Group (HRG) codes that are then reimbursed. Inconsistencies in documentation can result in inaccuracies in this process, with consequent implications for measuring activity, disease incidence and organisational performance. The aim of this study was to determine if clinician involvement increases accuracy in the coding of medical cases. Selected records of medical patients admitted to a London NHS trust between November and December 2016 were reviewed by a coding auditor and a clinician. Any changes to the codes and HRG tariff were noted. In total, 123 cases were considered. Changes in code were made on 68 instances, resulting in an overall increase in remuneration of £39,215; an average of £318 per patient. The primary HRG code was changed in 31 cases which accounted for £28,040 of the increase in tariff. In conclusion, clinician involvement can help with documentation ambiguities, thus improving the accuracy of the coding process in a medical setting. Although such collaborative working offers advantages for both the clinician and the coding team, further work is required to investigate the feasibility of this recommendation on a larger scale.