John Alexander - Academia.edu (original) (raw)
Papers by John Alexander
We acquired, federated and curated approximately one million new observations to the Avian Knowle... more We acquired, federated and curated approximately one million new observations to the Avian Knowledge Network. We used these new and existing observations to model the distribution and abundance of 26 species of land birds in the southern portion of the North Pacific Landscape Conservation Cooperative (NPLCC) region including CA, OR and WA. The models were based on climate and modeled vegetation. Using the models we created maps of the of the distribution and abundance of each species for current (late 20th century) conditions and projected the models to future (2070) based on five future regional climate models. The bird models were also used to create maps of conservation priorities for all species and for species indicative of four different habitat types: conifer forest, oak woodlands, grasslands and riparian forest. We created a web based decision support tool (http://data.prbo.org/apps/nplcc/) where the results from the project can be viewed, queried and downloaded, including r...
Circulation, Jan 17, 2015
Nature medicine, 2007
Loss of cone function in the central retina is a pivotal event in the development of severe visio... more Loss of cone function in the central retina is a pivotal event in the development of severe vision impairment for many prevalent blinding diseases. Complete achromatopsia is a genetic defect resulting in cone vision loss in 1 in 30,000 individuals. Using adeno-associated virus (AAV) gene therapy, we show that it is possible to target cones and rescue both the cone-mediated electroretinogram response and visual acuity in the Gnat2 ( cpfl3 ) mouse model of achromatopsia.
Drug news & perspectives, 2008
Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both bec... more Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both because cone photoreceptor diseases are severely vision limiting and because many retinal diseases that do not affect cones directly eventually lead to cone loss, the reason for eventual blindness. Human achromatopsia is a genetic disease of cones that renders them nonfunctional but otherwise intact. Thus, animal models of achromatopsia were used in conjunction with adeno-associated virus (AAV) vectors whose serotype efficiently transduces cones and with a promoter that limits transgene expression to cones. In the Gnat2(cpfl3) mouse model of one genetic form of human achromatopsia, we were able to demonstrate recovery of normal cone function and visual acuity after a single subretinal treatment of vector that supplied wild-type Gnat2 protein to cones. This validates the overall strategy of targeting cones using recombinant viral vectors and justifies a more complete examination of animal mo...
Australian and New Zealand Journal of Public Health, 2001
Objectives: To determine the health needs of public housing tenants, measured in terms of self-re... more Objectives: To determine the health needs of public housing tenants, measured in terms of self-reported health status, health risk factors and expressed need for health risk reduction intervention.Method: Face-to-face interviews were conducted with a randomly selected sample of public housing tenants in the Hunter Region of New South Wales.Results: Of 463 contactable tenants, 329 consented to participate in the study. Participants were 2.5 times more likely to rate their health as fair or poor relative to the community generally, and visited a doctor twice as often. The prevalence of smoking was more than twice that of the community generally, and the prevalence of falls was approximately three times greater. Risk of injury due to domestic violence was approximately six times greater, and the risk of injury due to violence in other locations was more than double that in the community. Between a quarter and a half of the participants requested support to reduce their health risks.Conclusions: The findings suggest that public housing tenants are one of the more severely health-compromised groups in the Australian community.Implications: An urgent need exists for public health initiatives that are directed at improving not only the current markedly poorer health status of public housing tenants, but also the greater prevalence of health risk factors that predict a likely continuation of such differentials into the future.
Background—The optimal anticoagulant regimen for percutaneous coronary intervention (PCI) remains... more Background—The optimal anticoagulant regimen for percutaneous coronary intervention (PCI) remains to be determined. Otamixaban, a selective and direct inhibitor of factor Xa, was investigated in patients undergoing nonurgent percutaneous coronary intervention. Methods and Results—In this double-blind, double-dummy, parallel-group, dose-ranging trial, 947 patients were randomly assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted unfractionated heparin (UFH) before percutaneous
The American Journal of Cardiology, 2015
Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythm... more Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythmia; yet, ECV use and outcomes in contemporary practice are unknown. We reviewed all nonemergent ECVs for atrial arrhythmias at a tertiary care center (2010 to 2013), stratifying patients by transesophageal echocardiography (TEE) use before ECV and comparing demographics, history, vitals, and laboratory studies. Outcomes included postprocedural success and complications and repeat cardioversion, rehospitalization, and death within 30 days. Overall, 1,017 patients underwent ECV, 760 (75%) for atrial fibrillation and 240 (24%) for atrial flutter; 633 underwent TEE before ECV and 384 did not. TEE recipients were more likely to be inpatients (74% vs 44%, p <0.001), have higher mean CHADS2 scores (2.6 vs 2.4, p = 0.03), and lower mean international normalized ratios (1.2 vs 2.1, p <0.001). Overall, 89 patients (8.8%) did not achieve sinus rhythm and 14 experienced procedural complications (1.4%). Within 30 days, 80 patients (7.9%) underwent repeat ECV, 113 (11%) were rehospitalized, and 14 (1.4%) died. Although ECV success was more common in patients who underwent TEE before ECV (77% vs 68%, p = 0.01), there were no differences in 30-day death or rehospitalization rates (11.1% vs 13.0%, p = 0.37). In multivariate analyses, higher pre-ECV heart rate was associated with increased rehospitalization or death (adjusted hazard ratio 1.15/10 beats/min, 95% confidence interval 1.07 to 1.24, p <0.001), whereas TEE use was associated with lower rates (adjusted hazard ratio 0.58, 95% confidence interval 0.39 to 0.86, p = 0.007). In conclusion, failures, complications, and rehospitalization after nonemergent ECV are common and associated more with patient condition than procedural characteristics. TEE use was associated with better clinical outcomes.
American Heart Journal, 2015
Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndr... more Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.
Nature reviews. Cardiology, 2013
The Journal of thoracic and cardiovascular surgery, 2014
American heart journal, 2014
Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and stud... more Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representative...
JAMA surgery, 2014
In vitro and animal model data suggest that intraoperative preservation solutions may influence e... more In vitro and animal model data suggest that intraoperative preservation solutions may influence endothelial function and vein graft failure (VGF) after coronary artery bypass graft (CABG) surgery. Clinical studies to validate these findings are lacking. To evaluate the effect of vein graft preservation solutions on VGF and clinical outcomes in patients undergoing CABG surgery. Data from the Project of Ex-Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) study, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 3014 patients at 107 US sites from August 1, 2002, through October 22, 2003, were used. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 planned vein grafts. Preservation of vein grafts in saline, blood, or buffered saline solutions. One-year angiographic VGF and 5-year rates of death, myocardial infarction, and subsequent revascularization. Most patients had grafts preserved i...
American heart journal, 2014
The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East ... more The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant no...
American heart journal, 2014
Hybrid coronary revascularization (HCR) involves minimally invasive left internal mammary artery ... more Hybrid coronary revascularization (HCR) involves minimally invasive left internal mammary artery to left anterior descending coronary artery grafting combined with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. The safety and efficacy of HCR among diabetic patients are unknown. Patients with diabetes were included who underwent HCR at a US academic center between October 2003 and September 2013. These patients were matched 1:5 to similar patients treated with coronary artery bypass grafting (CABG) using a propensity score (PS)-matching algorithm. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between HCR and inhospital complications, a composite measure of 30-day mortality, myocardial infarction and stroke, and up to 3-year all-cause mortality. Of 618 patients (HCR = 103; CABG = 515) in the PS-matched cohort, the 30-day composite of death, MI, or stroke after HCR and CABG wa...
Thorax, 2014
Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remain... more Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total ...
The Annals of thoracic surgery, 2014
Clinical chemistry, 2015
Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complement... more Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the conce...
American heart journal, 2015
We sought to assess the occurrence of events after blinded study drug discontinuation and transit... more We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of...
European heart journal, Jan 12, 2014
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (A... more In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 p...
We acquired, federated and curated approximately one million new observations to the Avian Knowle... more We acquired, federated and curated approximately one million new observations to the Avian Knowledge Network. We used these new and existing observations to model the distribution and abundance of 26 species of land birds in the southern portion of the North Pacific Landscape Conservation Cooperative (NPLCC) region including CA, OR and WA. The models were based on climate and modeled vegetation. Using the models we created maps of the of the distribution and abundance of each species for current (late 20th century) conditions and projected the models to future (2070) based on five future regional climate models. The bird models were also used to create maps of conservation priorities for all species and for species indicative of four different habitat types: conifer forest, oak woodlands, grasslands and riparian forest. We created a web based decision support tool (http://data.prbo.org/apps/nplcc/) where the results from the project can be viewed, queried and downloaded, including r...
Circulation, Jan 17, 2015
Nature medicine, 2007
Loss of cone function in the central retina is a pivotal event in the development of severe visio... more Loss of cone function in the central retina is a pivotal event in the development of severe vision impairment for many prevalent blinding diseases. Complete achromatopsia is a genetic defect resulting in cone vision loss in 1 in 30,000 individuals. Using adeno-associated virus (AAV) gene therapy, we show that it is possible to target cones and rescue both the cone-mediated electroretinogram response and visual acuity in the Gnat2 ( cpfl3 ) mouse model of achromatopsia.
Drug news & perspectives, 2008
Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both bec... more Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both because cone photoreceptor diseases are severely vision limiting and because many retinal diseases that do not affect cones directly eventually lead to cone loss, the reason for eventual blindness. Human achromatopsia is a genetic disease of cones that renders them nonfunctional but otherwise intact. Thus, animal models of achromatopsia were used in conjunction with adeno-associated virus (AAV) vectors whose serotype efficiently transduces cones and with a promoter that limits transgene expression to cones. In the Gnat2(cpfl3) mouse model of one genetic form of human achromatopsia, we were able to demonstrate recovery of normal cone function and visual acuity after a single subretinal treatment of vector that supplied wild-type Gnat2 protein to cones. This validates the overall strategy of targeting cones using recombinant viral vectors and justifies a more complete examination of animal mo...
Australian and New Zealand Journal of Public Health, 2001
Objectives: To determine the health needs of public housing tenants, measured in terms of self-re... more Objectives: To determine the health needs of public housing tenants, measured in terms of self-reported health status, health risk factors and expressed need for health risk reduction intervention.Method: Face-to-face interviews were conducted with a randomly selected sample of public housing tenants in the Hunter Region of New South Wales.Results: Of 463 contactable tenants, 329 consented to participate in the study. Participants were 2.5 times more likely to rate their health as fair or poor relative to the community generally, and visited a doctor twice as often. The prevalence of smoking was more than twice that of the community generally, and the prevalence of falls was approximately three times greater. Risk of injury due to domestic violence was approximately six times greater, and the risk of injury due to violence in other locations was more than double that in the community. Between a quarter and a half of the participants requested support to reduce their health risks.Conclusions: The findings suggest that public housing tenants are one of the more severely health-compromised groups in the Australian community.Implications: An urgent need exists for public health initiatives that are directed at improving not only the current markedly poorer health status of public housing tenants, but also the greater prevalence of health risk factors that predict a likely continuation of such differentials into the future.
Background—The optimal anticoagulant regimen for percutaneous coronary intervention (PCI) remains... more Background—The optimal anticoagulant regimen for percutaneous coronary intervention (PCI) remains to be determined. Otamixaban, a selective and direct inhibitor of factor Xa, was investigated in patients undergoing nonurgent percutaneous coronary intervention. Methods and Results—In this double-blind, double-dummy, parallel-group, dose-ranging trial, 947 patients were randomly assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted unfractionated heparin (UFH) before percutaneous
The American Journal of Cardiology, 2015
Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythm... more Electrical cardioversion (ECV) is recommended for rhythm control in patients with atrial arrhythmia; yet, ECV use and outcomes in contemporary practice are unknown. We reviewed all nonemergent ECVs for atrial arrhythmias at a tertiary care center (2010 to 2013), stratifying patients by transesophageal echocardiography (TEE) use before ECV and comparing demographics, history, vitals, and laboratory studies. Outcomes included postprocedural success and complications and repeat cardioversion, rehospitalization, and death within 30 days. Overall, 1,017 patients underwent ECV, 760 (75%) for atrial fibrillation and 240 (24%) for atrial flutter; 633 underwent TEE before ECV and 384 did not. TEE recipients were more likely to be inpatients (74% vs 44%, p <0.001), have higher mean CHADS2 scores (2.6 vs 2.4, p = 0.03), and lower mean international normalized ratios (1.2 vs 2.1, p <0.001). Overall, 89 patients (8.8%) did not achieve sinus rhythm and 14 experienced procedural complications (1.4%). Within 30 days, 80 patients (7.9%) underwent repeat ECV, 113 (11%) were rehospitalized, and 14 (1.4%) died. Although ECV success was more common in patients who underwent TEE before ECV (77% vs 68%, p = 0.01), there were no differences in 30-day death or rehospitalization rates (11.1% vs 13.0%, p = 0.37). In multivariate analyses, higher pre-ECV heart rate was associated with increased rehospitalization or death (adjusted hazard ratio 1.15/10 beats/min, 95% confidence interval 1.07 to 1.24, p <0.001), whereas TEE use was associated with lower rates (adjusted hazard ratio 0.58, 95% confidence interval 0.39 to 0.86, p = 0.007). In conclusion, failures, complications, and rehospitalization after nonemergent ECV are common and associated more with patient condition than procedural characteristics. TEE use was associated with better clinical outcomes.
American Heart Journal, 2015
Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndr... more Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.
Nature reviews. Cardiology, 2013
The Journal of thoracic and cardiovascular surgery, 2014
American heart journal, 2014
Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and stud... more Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities of IDMCs are expanding, perhaps due to increasing trial complexity and heterogeneity regarding medical, ethical, legal, regulatory, and financial issues. Second, no standard for IDMC operating procedures exists, and there is uncertainty about who should determine standards and whether standards should vary with trial size and design. Third, considerable variability in communication pathways exist across IDMC interfaces with regulatory agencies, academic coordinating centers, and sponsors. Finally, there has been a substantial increase in the number of RCTs using IDMCs, yet there is no set of qualifications to help guide the training and development of the next generation of IDMC members. Recently, an expert panel of representative...
JAMA surgery, 2014
In vitro and animal model data suggest that intraoperative preservation solutions may influence e... more In vitro and animal model data suggest that intraoperative preservation solutions may influence endothelial function and vein graft failure (VGF) after coronary artery bypass graft (CABG) surgery. Clinical studies to validate these findings are lacking. To evaluate the effect of vein graft preservation solutions on VGF and clinical outcomes in patients undergoing CABG surgery. Data from the Project of Ex-Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) study, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 3014 patients at 107 US sites from August 1, 2002, through October 22, 2003, were used. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 planned vein grafts. Preservation of vein grafts in saline, blood, or buffered saline solutions. One-year angiographic VGF and 5-year rates of death, myocardial infarction, and subsequent revascularization. Most patients had grafts preserved i...
American heart journal, 2014
The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East ... more The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant no...
American heart journal, 2014
Hybrid coronary revascularization (HCR) involves minimally invasive left internal mammary artery ... more Hybrid coronary revascularization (HCR) involves minimally invasive left internal mammary artery to left anterior descending coronary artery grafting combined with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. The safety and efficacy of HCR among diabetic patients are unknown. Patients with diabetes were included who underwent HCR at a US academic center between October 2003 and September 2013. These patients were matched 1:5 to similar patients treated with coronary artery bypass grafting (CABG) using a propensity score (PS)-matching algorithm. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between HCR and inhospital complications, a composite measure of 30-day mortality, myocardial infarction and stroke, and up to 3-year all-cause mortality. Of 618 patients (HCR = 103; CABG = 515) in the PS-matched cohort, the 30-day composite of death, MI, or stroke after HCR and CABG wa...
Thorax, 2014
Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remain... more Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total ...
The Annals of thoracic surgery, 2014
Clinical chemistry, 2015
Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complement... more Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the conce...
American heart journal, 2015
We sought to assess the occurrence of events after blinded study drug discontinuation and transit... more We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of...
European heart journal, Jan 12, 2014
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (A... more In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 p...