A CASE OF CHRONIC INTERNAL HYDROCEPHALUS.: Read before the Medical Society of the. District of Columbia, February 22, 1888.

n/

Statin prescribing for prevention of cardiovascular disease amongst people with severe mental illness: Cohort study in UK primary care

BACKGROUND: Severe mental illness (SMI) is associated with excess cardiovascular disease (CVD) morbidity, but little is known on provision of preventative interventions. We investigated statin initiation for primary CVD prevention in individuals with and without SMI. METHODS: We used primary care data from The Health Improvement Network from 2006 to 2015 for UK patients aged 30-99years with no pre-existing CVD conditions and selected individuals with schizophrenia (n=13,252) or bipolar disorder (n=11,994). In addition, we identified samples of individuals without schizophrenia (n=66,060) and bipolar disorder (n=59,765), but with similar age and gender distribution. Missing data on CVD covariates were estimated using multiple imputation. Statin prescribing differences between individuals with and without SMI were investigated using multivariable Poisson regression models. RESULTS: Initiation of statin prescribing was between 2 and 3 fold higher in people aged 30-59years with SMI than in those without after adjusting for CVD covariates. The rates in those aged 60-74years with SMI were similar or slightly higher relative to those without SMI. The incidence rate ratio (IRR) was 1.15 (95% CI 1.03-1.28) for bipolar disorder and 1.00 (0.91-1.11) for schizophrenia. The rate of statin prescribing was lower (IRR 0.81 (0.66-0.98)) amongst the oldest (aged 75+years) with schizophrenia relative to those without schizophrenia. CONCLUSIONS: Despite higher rates of new statin prescriptions to younger individuals with SMI relative to individuals without SMI, there was evidence of lower rates of statin initiation for older individuals with schizophrenia, and this group may benefit from additional measures to prevent CVD

Taking the Stem Cell Debate to the Public

In response to the Blackburn and Rowley essay on the President's Council on Bioethics, several thought-provoking opinions on ethical challenges in biomedical research are expressed by prominent stakeholder

Statin prescribing for people with severe mental illnesses: a staggered cohort study of 'real-world' impacts

OBJECTIVES: To estimate the 'real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder. DESIGN: Series of staggered cohorts. We estimated the effect of statin prescribing on CVD outcomes using a multivariable Poisson regression model or linear regression for cholesterol outcomes. SETTING: 587 general practice (GP) surgeries across the UK reporting data to The Health Improvement Network. PARTICIPANTS: All permanently registered GP patients aged 40-84 years between 2002 and 2012 who had a diagnosis of SMI. Exclusion criteria were pre-existing CVD, statin-contraindicating conditions or a statin prescription within the 24 months prior to the study start. EXPOSURE: One or more statin prescriptions during a 24-month 'baseline' period (vs no statin prescription during the same period). MAIN OUTCOME MEASURES: The primary outcome was combined first myocardial infarction and stroke. All-cause mortality and total cholesterol concentration were secondary outcomes. RESULTS: We identified 2944 statin users and 42 886 statin non-users across the staggered cohorts. Statin prescribing was not associated with significant reduction in CVD events (incident rate ratio 0.89; 95% CI 0.68 to 1.15) or all-cause mortality (0.89; 95% CI 0.78 to 1.02). Statin prescribing was, however, associated with statistically significant reductions in total cholesterol of 1.2 mmol/L (95% CI 1.1 to 1.3) for up to 2 years after adjusting for differences in baseline characteristics. On average, total cholesterol decreased from 6.3 to 4.6 in statin users and 5.4 to 5.3 mmol/L in non-users. CONCLUSIONS: We found that statin prescribing to people with SMI in UK primary care was effective for lipid modification but not CVD events. The latter finding may reflect insufficient power to detect a smaller effect size than that observed in randomised controlled trials of statins in people without SMI

High-Reynolds-number wall-modelled large eddy simulations of turbulent pipe flows using explicit and implicit subgrid stress treatments within a spectral element solver

We present explicit and implicit large eddy simulations for fully developed turbulent pipe flows using a continuous-Galerkin spectral element solver. On the one hand, the explicit stretched-vortex model (by Misra & Pullin [45] and Chung & Pullin [14]), accounts for an explicit treatment of unresolved stresses and is adapted to the high-order solver. On the other hand, an implicit approach based on a spectral vanishing viscosity technique is implemented. The latter implicit technique is modified to incorporate Chung & Pullin virtual-wall model instead of relying on implicit dissipative mechanisms near walls. This near-wall model is derived by averaging in the wall-normal direction and relying in local inner scaling to treat the time-dependence of the filtered wall-parallel velocity. The model requires space-time varying Dirichlet and Neumann boundary conditions for velocity and pressure respectively. We provide results and comparisons for the explicit and implicit subgrid treatments and show that both provide favourable results for pipe flows at Re_τ = 2×10^3 and Re_τ = 1.8×10^5 in terms of turbulence statistics. Additionally, we conclude that implicit simulations are enhanced when including the wall model and provide the correct statistics near walls

High-Reynolds-number wall-modelled large eddy simulations of turbulent pipe flows using explicit and implicit subgrid stress treatments within a spectral element solver

We present explicit and implicit large eddy simulations for fully developed turbulent pipe flows using a continuous-Galerkin spectral element solver. On the one hand, the explicit stretched-vortex model (by Misra & Pullin [45] and Chung & Pullin [14]), accounts for an explicit treatment of unresolved stresses and is adapted to the high-order solver. On the other hand, an implicit approach based on a spectral vanishing viscosity technique is implemented. The latter implicit technique is modified to incorporate Chung & Pullin virtual-wall model instead of relying on implicit dissipative mechanisms near walls. This near-wall model is derived by averaging in the wall-normal direction and relying in local inner scaling to treat the time-dependence of the filtered wall-parallel velocity. The model requires space-time varying Dirichlet and Neumann boundary conditions for velocity and pressure respectively. We provide results and comparisons for the explicit and implicit subgrid treatments and show that both provide favourable results for pipe flows at Re_τ = 2×10^3 and Re_τ = 1.8×10^5 in terms of turbulence statistics. Additionally, we conclude that implicit simulations are enhanced when including the wall model and provide the correct statistics near walls

Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England

BACKGROUND: Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care. METHODS AND FINDINGS: We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI. CONCLUSIONS: In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults