ABSTRACT We decompose the score statistic for testing for shared finite variance frailty in multi... more ABSTRACT We decompose the score statistic for testing for shared finite variance frailty in multivariate lifetime data into marginal and covariance-based terms. The null properties of the covariance-based statistic are derived in the context of parametric lifetime models. Its non-null properties are estimated using simulation and compared with those of the score test and two likelihood ratio tests when the underlying lifetime distribution is Weibull. Some examples are used to illustrate the covariance-based test. A case is made for using the covariance-based statistic as a simple diagnostic procedure for shared frailty in a parametric exploratory analysis of multivariate lifetime data and a link to the bivariate Clayton–Oakes copula model is shown.
indoors (p< 0.001), gender (p¼0.044), fracture side (p¼0.328). Admission haemoglobin, age, and ge... more indoors (p< 0.001), gender (p¼0.044), fracture side (p¼0.328). Admission haemoglobin, age, and gender contribute to the NHFS, so excluded for regression analysis. Following regression analysis (1) on 1-year mortality: NHFS (p¼0.0002), walking ability indoors (p¼0.1936), outdoors (p¼0.3348); (2) on survival period: NHFS (p¼0.0014), walking ability outdoors (p¼0.0037), indoors (p¼0.7118). Conclusions: Mortality risk is multi-factorial. We support the NHFS as a predictor for mortality risk at 1 year. Pre-admission walking ability outdoors with NHFS in a grid format can make an audit/research tool that standardises medical risk, and account for the likely prosthetic use.
Background We aimed to compare the performance of novices with three-dimensional (3D) versus two-... more Background We aimed to compare the performance of novices with three-dimensional (3D) versus two-dimensional (2D) laparoscopy using Fundamentals of Laparoscopic Surgery (FLS) tasks. Methods Fifty-six novices with no uncorrected visual problems were randomly allocated to 2D and 3D groups. All candidates practiced FLS tasks on a box trainer until they achieved proficiency. Their performance was assessed by considering completion time, number of repetitions, and number of errors following the validated FLS proficiency criteria.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 14, 2016
Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast can... more Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 pr...
The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclea... more The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS). From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either DAiS or DAdS. They were stratified for performance status, presence of bone metastases, and previous normalisation of prostate-specific antigen (PSA) to androgen deprivation. The study end points were the proportion of patients achieving a 50% PSA response, progression-free survival (PFS), overall survival, and quality of life. Intention-to-treat analysis was carried out. The effect of treatment was studied first by Kaplan-Meier curves and log-rank test, and finally through multivariable stratified Cox's proporti...
Background and Purpose-Data are lacking on the differences in hemorrhagic stroke incidence betwee... more Background and Purpose-Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. Methods-First-ever stroke patients were drawn from a prospective community stroke register based in a multiethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression.
Journal of Neurology, Neurosurgery & Psychiatry, 2008
To identify the predictors of long-term survival after haemorrhagic stroke. Data were collected w... more To identify the predictors of long-term survival after haemorrhagic stroke. Data were collected within the population-based South London Stroke Register covering a multiethnic source population of 271,817 inhabitants (2001) in South London. Death data were collected at post-stroke follow-up. The impact of patients&amp;amp;amp;amp;amp;amp;#39; demographic and clinical characteristics, ethnic origin, pre-stroke risk factors and acute treatment on long-term survival were investigated. Survival methods included Kaplan-Meier curves and Cox&amp;amp;amp;amp;amp;amp;#39;s proportional hazards model. Between January 1995 and December 2004, a total of 566 patients with first-ever haemorrhagic stroke (395 primary intracerebral haemorrhage; 171 subarachnoid haemorrhage) were registered. Mean age was 62.3 years; 365 (64.5%) were white, 132 (23.3%) were black and 69 (12.2%) were other or unknown ethnic origin; there were 1340 person-years of follow-up. After multivariable adjustment, age (p&amp;amp;amp;amp;amp;amp;lt;0.001) and having diabetes (hazard ratio (HR), 1.69; 95% CI 1.06-2.70) were associated with increased risk of death. Patients with severe stroke (Glasgow Coma Scale (GCS) &amp;amp;amp;amp;amp;amp;lt;9) had an increased risk of death (HR 6.5; 95% CI 4.68 to 8.90) compared with those with mild stroke (GCS &amp;amp;amp;amp;amp;amp;gt;12). Treatment on a stroke unit reduced the long-term risk of death (HR 0.70; 95% CI 0.50 to 0.98). Black patients had a reduced risk of death (HR 0.62; 95% CI 0.42 to 0.92) compared with white patients. Age, diabetes, stroke severity and stroke unit care influenced the long-term risk of death after haemorrhagic stroke. An independent survival advantage was observed in black patients. These factors can be utilised for clinical predictions but the cause of the observations in black patients remains unclear.
ABSTRACT We decompose the score statistic for testing for shared finite variance frailty in multi... more ABSTRACT We decompose the score statistic for testing for shared finite variance frailty in multivariate lifetime data into marginal and covariance-based terms. The null properties of the covariance-based statistic are derived in the context of parametric lifetime models. Its non-null properties are estimated using simulation and compared with those of the score test and two likelihood ratio tests when the underlying lifetime distribution is Weibull. Some examples are used to illustrate the covariance-based test. A case is made for using the covariance-based statistic as a simple diagnostic procedure for shared frailty in a parametric exploratory analysis of multivariate lifetime data and a link to the bivariate Clayton–Oakes copula model is shown.
indoors (p< 0.001), gender (p¼0.044), fracture side (p¼0.328). Admission haemoglobin, age, and ge... more indoors (p< 0.001), gender (p¼0.044), fracture side (p¼0.328). Admission haemoglobin, age, and gender contribute to the NHFS, so excluded for regression analysis. Following regression analysis (1) on 1-year mortality: NHFS (p¼0.0002), walking ability indoors (p¼0.1936), outdoors (p¼0.3348); (2) on survival period: NHFS (p¼0.0014), walking ability outdoors (p¼0.0037), indoors (p¼0.7118). Conclusions: Mortality risk is multi-factorial. We support the NHFS as a predictor for mortality risk at 1 year. Pre-admission walking ability outdoors with NHFS in a grid format can make an audit/research tool that standardises medical risk, and account for the likely prosthetic use.
Background We aimed to compare the performance of novices with three-dimensional (3D) versus two-... more Background We aimed to compare the performance of novices with three-dimensional (3D) versus two-dimensional (2D) laparoscopy using Fundamentals of Laparoscopic Surgery (FLS) tasks. Methods Fifty-six novices with no uncorrected visual problems were randomly allocated to 2D and 3D groups. All candidates practiced FLS tasks on a box trainer until they achieved proficiency. Their performance was assessed by considering completion time, number of repetitions, and number of errors following the validated FLS proficiency criteria.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 14, 2016
Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast can... more Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 pr...
The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclea... more The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS). From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either DAiS or DAdS. They were stratified for performance status, presence of bone metastases, and previous normalisation of prostate-specific antigen (PSA) to androgen deprivation. The study end points were the proportion of patients achieving a 50% PSA response, progression-free survival (PFS), overall survival, and quality of life. Intention-to-treat analysis was carried out. The effect of treatment was studied first by Kaplan-Meier curves and log-rank test, and finally through multivariable stratified Cox's proporti...
Background and Purpose-Data are lacking on the differences in hemorrhagic stroke incidence betwee... more Background and Purpose-Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. Methods-First-ever stroke patients were drawn from a prospective community stroke register based in a multiethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression.
Journal of Neurology, Neurosurgery & Psychiatry, 2008
To identify the predictors of long-term survival after haemorrhagic stroke. Data were collected w... more To identify the predictors of long-term survival after haemorrhagic stroke. Data were collected within the population-based South London Stroke Register covering a multiethnic source population of 271,817 inhabitants (2001) in South London. Death data were collected at post-stroke follow-up. The impact of patients&amp;amp;amp;amp;amp;amp;#39; demographic and clinical characteristics, ethnic origin, pre-stroke risk factors and acute treatment on long-term survival were investigated. Survival methods included Kaplan-Meier curves and Cox&amp;amp;amp;amp;amp;amp;#39;s proportional hazards model. Between January 1995 and December 2004, a total of 566 patients with first-ever haemorrhagic stroke (395 primary intracerebral haemorrhage; 171 subarachnoid haemorrhage) were registered. Mean age was 62.3 years; 365 (64.5%) were white, 132 (23.3%) were black and 69 (12.2%) were other or unknown ethnic origin; there were 1340 person-years of follow-up. After multivariable adjustment, age (p&amp;amp;amp;amp;amp;amp;lt;0.001) and having diabetes (hazard ratio (HR), 1.69; 95% CI 1.06-2.70) were associated with increased risk of death. Patients with severe stroke (Glasgow Coma Scale (GCS) &amp;amp;amp;amp;amp;amp;lt;9) had an increased risk of death (HR 6.5; 95% CI 4.68 to 8.90) compared with those with mild stroke (GCS &amp;amp;amp;amp;amp;amp;gt;12). Treatment on a stroke unit reduced the long-term risk of death (HR 0.70; 95% CI 0.50 to 0.98). Black patients had a reduced risk of death (HR 0.62; 95% CI 0.42 to 0.92) compared with white patients. Age, diabetes, stroke severity and stroke unit care influenced the long-term risk of death after haemorrhagic stroke. An independent survival advantage was observed in black patients. These factors can be utilised for clinical predictions but the cause of the observations in black patients remains unclear.
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