Graeme Hickey | Independent Researcher (original) (raw)
Papers by Graeme Hickey
Statistical methods in medical research, Jan 26, 2016
A clinical prediction model is a tool for predicting healthcare outcomes, usually within a specif... more A clinical prediction model is a tool for predicting healthcare outcomes, usually within a specific population and context. A common approach is to develop a new clinical prediction model for each population and context; however, this wastes potentially useful historical information. A better approach is to update or incorporate the existing clinical prediction models already developed for use in similar contexts or populations. In addition, clinical prediction models commonly become miscalibrated over time, and need replacing or updating. In this article, we review a range of approaches for re-using and updating clinical prediction models; these fall in into three main categories: simple coefficient updating, combining multiple previous clinical prediction models in a meta-model and dynamic updating of models. We evaluated the performance (discrimination and calibration) of the different strategies using data on mortality following cardiac surgery in the United Kingdom: We found th...
BMJ (Clinical research ed.), 2016
To estimate the potential impact of universal screening for primary prevention of cardiovascular... more To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. Synthetic population with similar characteristics to the community dwelling population of England. Synthetic people with traits informed by the health survey for England. Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple de...
Innovations (Philadelphia, Pa.), Jan 26, 2016
Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective... more Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR). Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006-2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used. Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%-3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%-4.3%; P = 0.752]...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2016
The Annals of thoracic surgery, Jan 26, 2016
To facilitate patient choice and the risk adjustment of consultant outcomes in aortic operations,... more To facilitate patient choice and the risk adjustment of consultant outcomes in aortic operations, reliable predictive tools are required. Our objective was to develop a risk prediction model for in-hospital mortality after operation on the proximal aorta. Data for 8641 consecutive UK patients undergoing proximal aortic operation from the National Institute for Cardiovascular Outcomes Research database from April 2007 to March 2013 were analyzed. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. Model calibration and discrimination were assessed. In-hospital mortality was 4.6% in elective operations and 16.5% in nonelective operations. In the elective model, previous cardiac operation (adjusted odds ratio [OR] 4.1, 95% confidence interval [CI]: 3.0 to 4.7) and ejection fraction greater than 30% (adjusted OR 2.3, 95% CI: 1.7 to 3.1) were the strongest predictors of mortality (p < 0.001). The area under the receiver operating cha...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 18, 2015
To determine if the use of cardiopulmonary bypass is associated with all-cause in-hospital and mi... more To determine if the use of cardiopulmonary bypass is associated with all-cause in-hospital and mid-term survival for patients undergoing left internal mammary artery (LIMA) to left anterior descending (LAD) coronary artery bypass grafting (CABG) for single coronary vessel disease. Data from the National Adult Cardiac Surgery Audit registry for all elective and urgent isolated CABG procedures performed between April 2003 and March 2013 in first-time cardiac surgery patients were extracted. Experienced surgeons (those with ≥300 records) were classified by their technique preference (as 'off-pump preference', 'mixed practice', 'on-pump preference') based on their entire isolated CABG data. In-hospital mortality and time to death were analysed using logistic and Cox proportional hazards regression models, respectively. From a total of 3402 records, 65.5% were performed off-pump. There were 16 (0.47%) in-hospital deaths: 6 (0.51%) in the on-pump group and 10 (0.45...
Journal of the American College of Cardiology, 2015
BMJ open, 2015
Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac ... more Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac surgery risk prediction models. The objective was to investigate geographical variations in social deprivation of patients undergoing cardiac surgery and identify whether social deprivation is an independent predictor of outcomes. National Adult Cardiac Surgery Audit data for coronary artery bypass graft (CABG), or valve surgery performed in England between April 2003 and March 2013, were analysed. Base hospitals in England were divided into geographical regions. Social deprivation was measured by quintile groups of the index of multiple deprivation (IMD) score with the first quintile group (Q1) being the least, and the last quintile group (Q5) the most deprived group. In-hospital mortality and midterm survival were analysed using mixed effects logistic, and stratified Cox proportional hazards regression models respectively. 240,221 operations were analysed. There was substantial regiona...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 13, 2015
The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 20... more The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 2007. This study presents the subsequent national activity and outcomes for both TAVI and aortic valve replacement (AVR). Data for all AVR and TAVI procedures between January 2006 and December 2012 in England and Wales were included. The number of procedures, patient characteristics, in-hospital and 30-day mortality, postoperative length of stay (PLOS) and survival were analysed separately for: isolated AVR; AVR + coronary artery bypass graft (CABG) surgery; AVR + other surgery and TAVI. The number of TAVIs increased from 66 in 2007 (0.8% of all implants) to 1186 in 2012 (10.9% of all implants). AVR activity also increased over the study period. TAVI patients were older and had a higher mean logistic EuroSCORE than all AVR groups. The 30-day mortality rates were 2.1% for isolated AVR, 3.9% for AVR + CABG, 7.7% for AVR + other surgery and 6.2% for TAVI. In-hospital mortality has significant...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 12, 2015
As part of the peer review process for the European Journal of Cardio-Thoracic Surgery (EJCTS) an... more As part of the peer review process for the European Journal of Cardio-Thoracic Surgery (EJCTS) and the Interactive CardioVascular and Thoracic Surgery (ICVTS), a statistician reviews any manuscript that includes a statistical analysis. To facilitate authors considering submitting a manuscript and to make it clearer about the expectations of the statistical reviewers, we present up-to-date guidelines for authors on statistical and data reporting specifically in these journals. The number of statistical methods used in the cardiothoracic literature is vast, as are the ways in which data are presented. Therefore, we narrow the scope of these guidelines to cover the most common applications submitted to the EJCTS and ICVTS, focusing in particular on those that the statistical reviewers most frequently comment on.
PloS one, 2015
Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statin... more Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups. This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual 'no statins' scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-...
Immunology and cell biology, Jan 23, 2014
Toxoplasma gondii is a highly prevalent intracellular protozoan parasite that causes severe disea... more Toxoplasma gondii is a highly prevalent intracellular protozoan parasite that causes severe disease in congenitally infected or immunocompromised hosts. T. gondii is capable of invading immune cells and it has been suggested that the parasite harnesses the migratory pathways of these cells to spread through the body. Although in vitro evidence suggests that the parasite further enhances its spread by inducing a hypermotility phenotype in parasitized immune cells, in vivo evidence for this phenomenon is scarce. Here we use a physiologically relevant oral model of T. gondii infection, in conjunction with two-photon laser scanning microscopy, to address this issue. We found that a small proportion of natural killer (NK) cells in mesenteric lymph nodes contained parasites. Compared with uninfected 'bystander' NK cells, these infected NK cells showed faster, more directed and more persistent migratory behavior. Consistent with this, infected NK cells showed impaired spreading and...
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 2014
A number of contemporary risk prediction models for mortality following elective abdominal aortic... more A number of contemporary risk prediction models for mortality following elective abdominal aortic aneurysm (AAA) repair have been developed. Before a model is used either in clinical practice or to risk-adjust surgical outcome data it is important that its performance is assessed in external validation studies. The British Aneurysm Repair (BAR) score, Medicare, and Vascular Governance North West (VGNW) models were validated using an independent prospectively collected sample of multicentre clinical audit data. Consecutive, data on 1,124 patients undergoing elective AAA repair at 17 hospitals in the north-west of England and Wales between April 2011 and March 2013 were analysed. The outcome measure was in-hospital mortality. Model calibration (observed to expected ratio with chi-square test, calibration plots, calibration intercept and slope) and discrimination (area under receiver operating characteristic curve [AUC]) were assessed in the overall cohort and procedural subgroups. The...
Journal of vascular surgery, 2013
The Journal of thoracic and cardiovascular surgery, 2016
Clinical risk-prediction models serve an important role in healthcare. They are used for clinical... more Clinical risk-prediction models serve an important role in healthcare. They are used for clinical decision-making and measuring the performance of healthcare providers. To establish confidence in a model, external model validation is imperative. When designing such an external model validation study, thought must be given to patient selection, risk factor and outcome definitions, missing data, and the transparent reporting of the analysis. In addition, there are a number of statistical methods available for external model validation. Execution of a rigorous external validation study rests in proper study design, application of suitable statistical methods, and transparent reporting.
Preventive Veterinary Medicine, 2015
Please cite this article as: Hickey, G.L., Diggle, P.J., McNeilly, T.N., Tongue, S.C., Chase-Topp... more Please cite this article as: Hickey, G.L., Diggle, P.J., McNeilly, T.N., Tongue, S.C., Chase-Topping, M.E., Williams, D.J.L.,The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol, Preventive Veterinary Medicine (2015), http://dx.
Statistical methods in medical research, Jan 26, 2016
A clinical prediction model is a tool for predicting healthcare outcomes, usually within a specif... more A clinical prediction model is a tool for predicting healthcare outcomes, usually within a specific population and context. A common approach is to develop a new clinical prediction model for each population and context; however, this wastes potentially useful historical information. A better approach is to update or incorporate the existing clinical prediction models already developed for use in similar contexts or populations. In addition, clinical prediction models commonly become miscalibrated over time, and need replacing or updating. In this article, we review a range of approaches for re-using and updating clinical prediction models; these fall in into three main categories: simple coefficient updating, combining multiple previous clinical prediction models in a meta-model and dynamic updating of models. We evaluated the performance (discrimination and calibration) of the different strategies using data on mortality following cardiac surgery in the United Kingdom: We found th...
BMJ (Clinical research ed.), 2016
To estimate the potential impact of universal screening for primary prevention of cardiovascular... more To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. Synthetic population with similar characteristics to the community dwelling population of England. Synthetic people with traits informed by the health survey for England. Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple de...
Innovations (Philadelphia, Pa.), Jan 26, 2016
Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective... more Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR). Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006-2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used. Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%-3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%-4.3%; P = 0.752]...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2016
The Annals of thoracic surgery, Jan 26, 2016
To facilitate patient choice and the risk adjustment of consultant outcomes in aortic operations,... more To facilitate patient choice and the risk adjustment of consultant outcomes in aortic operations, reliable predictive tools are required. Our objective was to develop a risk prediction model for in-hospital mortality after operation on the proximal aorta. Data for 8641 consecutive UK patients undergoing proximal aortic operation from the National Institute for Cardiovascular Outcomes Research database from April 2007 to March 2013 were analyzed. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. Model calibration and discrimination were assessed. In-hospital mortality was 4.6% in elective operations and 16.5% in nonelective operations. In the elective model, previous cardiac operation (adjusted odds ratio [OR] 4.1, 95% confidence interval [CI]: 3.0 to 4.7) and ejection fraction greater than 30% (adjusted OR 2.3, 95% CI: 1.7 to 3.1) were the strongest predictors of mortality (p < 0.001). The area under the receiver operating cha...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 18, 2015
To determine if the use of cardiopulmonary bypass is associated with all-cause in-hospital and mi... more To determine if the use of cardiopulmonary bypass is associated with all-cause in-hospital and mid-term survival for patients undergoing left internal mammary artery (LIMA) to left anterior descending (LAD) coronary artery bypass grafting (CABG) for single coronary vessel disease. Data from the National Adult Cardiac Surgery Audit registry for all elective and urgent isolated CABG procedures performed between April 2003 and March 2013 in first-time cardiac surgery patients were extracted. Experienced surgeons (those with ≥300 records) were classified by their technique preference (as 'off-pump preference', 'mixed practice', 'on-pump preference') based on their entire isolated CABG data. In-hospital mortality and time to death were analysed using logistic and Cox proportional hazards regression models, respectively. From a total of 3402 records, 65.5% were performed off-pump. There were 16 (0.47%) in-hospital deaths: 6 (0.51%) in the on-pump group and 10 (0.45...
Journal of the American College of Cardiology, 2015
BMJ open, 2015
Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac ... more Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac surgery risk prediction models. The objective was to investigate geographical variations in social deprivation of patients undergoing cardiac surgery and identify whether social deprivation is an independent predictor of outcomes. National Adult Cardiac Surgery Audit data for coronary artery bypass graft (CABG), or valve surgery performed in England between April 2003 and March 2013, were analysed. Base hospitals in England were divided into geographical regions. Social deprivation was measured by quintile groups of the index of multiple deprivation (IMD) score with the first quintile group (Q1) being the least, and the last quintile group (Q5) the most deprived group. In-hospital mortality and midterm survival were analysed using mixed effects logistic, and stratified Cox proportional hazards regression models respectively. 240,221 operations were analysed. There was substantial regiona...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 13, 2015
The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 20... more The first transcatheter aortic valve implantation (TAVI) in England and Wales was performed in 2007. This study presents the subsequent national activity and outcomes for both TAVI and aortic valve replacement (AVR). Data for all AVR and TAVI procedures between January 2006 and December 2012 in England and Wales were included. The number of procedures, patient characteristics, in-hospital and 30-day mortality, postoperative length of stay (PLOS) and survival were analysed separately for: isolated AVR; AVR + coronary artery bypass graft (CABG) surgery; AVR + other surgery and TAVI. The number of TAVIs increased from 66 in 2007 (0.8% of all implants) to 1186 in 2012 (10.9% of all implants). AVR activity also increased over the study period. TAVI patients were older and had a higher mean logistic EuroSCORE than all AVR groups. The 30-day mortality rates were 2.1% for isolated AVR, 3.9% for AVR + CABG, 7.7% for AVR + other surgery and 6.2% for TAVI. In-hospital mortality has significant...
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Jan 12, 2015
As part of the peer review process for the European Journal of Cardio-Thoracic Surgery (EJCTS) an... more As part of the peer review process for the European Journal of Cardio-Thoracic Surgery (EJCTS) and the Interactive CardioVascular and Thoracic Surgery (ICVTS), a statistician reviews any manuscript that includes a statistical analysis. To facilitate authors considering submitting a manuscript and to make it clearer about the expectations of the statistical reviewers, we present up-to-date guidelines for authors on statistical and data reporting specifically in these journals. The number of statistical methods used in the cardiothoracic literature is vast, as are the ways in which data are presented. Therefore, we narrow the scope of these guidelines to cover the most common applications submitted to the EJCTS and ICVTS, focusing in particular on those that the statistical reviewers most frequently comment on.
PloS one, 2015
Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statin... more Serum total cholesterol is one of the major targets for cardiovascular disease prevention. Statins are effective for cholesterol control in individual patients. At the population level, however, their contribution to total cholesterol decline remains unclear. The aim of this study was to quantify the contribution of statins to the observed fall in population mean cholesterol levels in England over the past two decades, and explore any differences between socioeconomic groups. This is a modelling study based on data from the Health Survey for England. We analysed changes in observed mean total cholesterol levels in the adult England population between 1991-92 (baseline) and 2011-12. We then compared the observed changes with a counterfactual 'no statins' scenario, where the impact of statins on population total cholesterol was estimated and removed. We estimated uncertainty intervals (UI) using Monte Carlo simulation, where confidence intervals (CI) were impractical. In 2011-...
Immunology and cell biology, Jan 23, 2014
Toxoplasma gondii is a highly prevalent intracellular protozoan parasite that causes severe disea... more Toxoplasma gondii is a highly prevalent intracellular protozoan parasite that causes severe disease in congenitally infected or immunocompromised hosts. T. gondii is capable of invading immune cells and it has been suggested that the parasite harnesses the migratory pathways of these cells to spread through the body. Although in vitro evidence suggests that the parasite further enhances its spread by inducing a hypermotility phenotype in parasitized immune cells, in vivo evidence for this phenomenon is scarce. Here we use a physiologically relevant oral model of T. gondii infection, in conjunction with two-photon laser scanning microscopy, to address this issue. We found that a small proportion of natural killer (NK) cells in mesenteric lymph nodes contained parasites. Compared with uninfected 'bystander' NK cells, these infected NK cells showed faster, more directed and more persistent migratory behavior. Consistent with this, infected NK cells showed impaired spreading and...
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 2014
A number of contemporary risk prediction models for mortality following elective abdominal aortic... more A number of contemporary risk prediction models for mortality following elective abdominal aortic aneurysm (AAA) repair have been developed. Before a model is used either in clinical practice or to risk-adjust surgical outcome data it is important that its performance is assessed in external validation studies. The British Aneurysm Repair (BAR) score, Medicare, and Vascular Governance North West (VGNW) models were validated using an independent prospectively collected sample of multicentre clinical audit data. Consecutive, data on 1,124 patients undergoing elective AAA repair at 17 hospitals in the north-west of England and Wales between April 2011 and March 2013 were analysed. The outcome measure was in-hospital mortality. Model calibration (observed to expected ratio with chi-square test, calibration plots, calibration intercept and slope) and discrimination (area under receiver operating characteristic curve [AUC]) were assessed in the overall cohort and procedural subgroups. The...
Journal of vascular surgery, 2013
The Journal of thoracic and cardiovascular surgery, 2016
Clinical risk-prediction models serve an important role in healthcare. They are used for clinical... more Clinical risk-prediction models serve an important role in healthcare. They are used for clinical decision-making and measuring the performance of healthcare providers. To establish confidence in a model, external model validation is imperative. When designing such an external model validation study, thought must be given to patient selection, risk factor and outcome definitions, missing data, and the transparent reporting of the analysis. In addition, there are a number of statistical methods available for external model validation. Execution of a rigorous external validation study rests in proper study design, application of suitable statistical methods, and transparent reporting.
Preventive Veterinary Medicine, 2015
Please cite this article as: Hickey, G.L., Diggle, P.J., McNeilly, T.N., Tongue, S.C., Chase-Topp... more Please cite this article as: Hickey, G.L., Diggle, P.J., McNeilly, T.N., Tongue, S.C., Chase-Topping, M.E., Williams, D.J.L.,The feasibility of testing whether Fasciola hepatica is associated with increased risk of verocytotoxin producing Escherichia coli O157 from an existing study protocol, Preventive Veterinary Medicine (2015), http://dx.