The impact of statin use on the efficacy of abiraterone acetate in patients with castration‐resistant prostate cancer

Background

Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO‐mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy.

Methods

We queried two institutional clinical databases (Dana‐Farber Cancer Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan‐Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors.

Results

Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79, 95%CI: 0.57‐1.09, P = 0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69‐1.16, P = 0.38) in the statin users versus non‐users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57‐1.10).

Conclusions

Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide‐ and docetaxel‐naïve JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.     

Effects of prior beta-blocker therapy on clinical outcomes after primary coronary angioplasty for acute myocardial infarction

We hypothesized that pretreatment with beta blockers may improve clinical outcomes after primary angioplasty for acute myocardial infarction. We pooled clinical, angiographic, and outcomes data on 2,537 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI), PAMI-2, and Stent PAMI trials. We classified patients into a beta group (n = 1,132) if they received beta-blocker therapy before primary angioplasty or a no-beta group (n = 1,405) if they did not. We evaluated procedural complications and in-hospital and 1-year outcomes (death and major adverse cardiac events [death, reinfarction, target vessel revascularization, or stroke]) between groups. Beta patients were younger, had higher systolic blood pressure and heart rate, and were more likely to be in Killip class I at admission. They had lower left ventricular ejection fraction, greater door-to-balloon time, greater likelihood of having a left anterior descending artery culprit lesion, but a similar incidence of Thrombolysis In Myocardial Infarction 3 flow after angioplasty (92.6% vs 92.7%, p = 0.91). The beta group had less procedural complications (23% vs 34%, p <0.0001) and a lower incidence of death (1.8% vs 3.7%, p = 0.0035) and major adverse cardiac events (5.5% vs 7.8%, p = 0.027) during hospitalization. At 1 year, mortality remained lower in beta patients (4.9% vs 6.7%, log-rank p = 0.055). After adjustment for baseline differences, beta patients had significantly lower in-hospital mortality (odds ratio 0.41; 95% confidence interval 0.20 to 0.84; p <0.0148) and nonsignificantly lower 1-year mortality (odds ratio 0.72; 95% confidence interval 0.47 to 1.08; p = 0.11). Thus, pretreatment with beta blockers has an independent beneficial effect on short-term clinical outcomes in patients undergoing primary angioplasty for acute myocardial infarction.     

Usefulness of the presence of peripheral vascular disease in predicting mortality in acute myocardial infarction patients treated with primary angioplasty (from the Primary Angioplasty in Myocardial Infarction Database)

Patients with acute myocardial infarction (AMI) often have multiple co-morbidities that influence outcome. We sought to evaluate the impact of peripheral vascular disease (PVD) on the outcome of patients with AMI treated with primary angioplasty. We evaluated 3,716 patients with AMI who underwent emergency catheterization with planned primary angioplasty in the Primary Angioplasty in Myocardial Infarction trials. Patients with a history of PVD (claudication, stroke, or transient ischemic attack) were compared with patients without PVD. Of the 3,716 patients, 394 (10.6%) had PVD and were older, more often women, and more frequently had a history of diabetes mellitus, hypertension, smoking, congestive heart failure, angina, myocardial infarction, and coronary revascularization. They presented more often with a heart rate >100 beats/min, Killip class >1, lower ejection fraction, and multivessel disease. No difference was found in stent use, final percentage of stenosis, or Thrombolysis In Myocardial Infarction 3 flow. Patients with PVD had a twofold increased in-hospital mortality (5.3% vs 2.6%, p = 0.0021). The difference remained significant at 1 month, 6 months, and 1 year (12.6% vs 6%, p < 0.0001). In multivariate logistic regression analysis, a history of PVD was an independent predictor of in-hospital mortality and death at 1 year (odds ratio 1.64, 95% confidence interval 1.04 to 2.57, p = 0.032). In conclusion, patients with AMI with PVD have increased co-morbidities and higher mortality despite treatment with primary angioplasty. The presence of PVD is an independent predictor of in-hospital mortality and death at 1 year.     

Prediction of one-year mortality among 30-day survivors after primary percutaneous coronary interventions

Little information exists on the features that influence risk factors for death at 1 year among 30-day survivors of ST-elevation myocardial infarction (STEMI) that is treated with primary percutaneous coronary intervention (PCI). Accordingly, we examined 3,280 patients with STEMI who were enrolled in Stent-PAMI and CADILLAC trials, were treated with primary PCI, and survived >30 days after STEMI. Death at 1 year occurred in 74 patients (2.3%) who survived >30 days after their index STEMI. Patients who died at 1 year were more likely to be older and women and have lower body weight and greater prevalence of previous stroke. Similarly, the sum of ST elevations, 3-vessel or left anterior coronary disease, and final Thrombolysis In Myocardial Infarction grade <3 flow was higher, whereas left ventricular ejection fraction was lower among patients who died versus those who survived. The multivariate logistic regression model identified age >70 years (odds ratio [OR] 3.3 95% confidence interval [CI] 1.9 to 5.7), weight <80 kg (OR 1.9, 95% CI 1.1 to 3.6), any tachyarrhythmia during index hospitalization (defined as ventricular or supraventricular tachycardia that required treatment) (OR 2.4, 95% CI 1.2 to 4.8), number of diseased coronary arteries (OR 1.5, 95% CI 1.1 to 2.1), and left ventricular ejection fraction (each 10% decrease, OR 1.5, 95% CI 1.2 to 1.8) as factors independently associated with risk of death at 1 year among 30-day survivors. In conclusion, our study provides a method for clinicians to advise patients who are treated with primary PCI and survive the acute phase of STEMI with regard to patients' long-term prognosis, thus enhancing planning and setting up of realistic expectations.     

Comparison of outcomes of diabetic and nondiabetic patients undergoing primary angioplasty for acute myocardial infarction

We sought to determine whether diabetes mellitus independently conferred poor prognosis in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). In 3,742 patients enrolled in the Primary Angioplasty in Myocardial Infarction (PAMI) studies with the intention of undergoing primary PCI, we compared in-hospital mortality, 6-month mortality, and 6-month major adverse cardiovascular events (MACEs), i.e., composite of death, reinfarction, or ischemic target vessel revascularization (TVR), between diabetics (n = 626, 17%) and nondiabetics (n = 3,116, 83%). We evaluated the independent impact of diabetes on outcomes after adjustment for baseline clinical and angiographic differences. Diabetics had worse baseline clinical characteristics, longer pain onset-to-hospital arrival time, and longer door-to-balloon time. They had more multivessel coronary disease and lower left ventricular ejection fractions, but better baseline Thrombolysis In Myocardial Infarction (TIMI) flow. Diabetics underwent primary PCI less often (88% vs 91%, p = 0.01). During the index hospitalization, diabetics were more likely to die (4.6% vs 2.6%, p = 0.005). During 6-month follow-up, diabetics had higher incidences of death (8.1% vs 4.2%, p <0.0001) and MACEs (18% vs 14%, p = 0.036). In multivariate analysis, diabetes was independently associated with 6-month mortality (hazard ratio 1.53, 95% confidence interval 1.03 to 2.26, p = 0.03), but not with in-hospital mortality or 6-month MACEs. We conclude that diabetics with AMI have less favorable baseline characteristics and are less likely to undergo primary PCI than nondiabetics. Despite excellent angiographic results, diabetics had significantly worse 6-month mortality.     

Silence, power and communication in the operating room

Title.  Silence, power and communication in the operating room.
Aim.  This paper is a report of a study conducted to explore whether a 1- to 3-minute preoperative interprofessional team briefing with a structured checklist was an effective way to support communication in the operating room.
Background.  Previous research suggests that nurses often feel constrained in their ability to communicate with physicians. Previous research on silence and power suggests that silence is not only a reflection of powerlessness or passivity, and that silence and speech are not opposites, but closely interrelated.
Methods.  We conducted a retrospective study of silences observed in communication between nurses and surgeons in a multi-site observational study of interprofessional communication in the operating room. Over 700 surgical procedures were observed from 2005–2007. Instances of communication characterized by unresolved or unarticulated issues were identified in field notes and analysed from a critical ethnography perspective.
Findings.  We identified three forms of recurring 'silences': absence of communication; not responding to queries or requests; and speaking quietly. These silences may be defensive or strategic, and they may be influenced by larger institutional and structural power dynamics as well as by the immediate situational context.
Conclusions.  There is no single answer to the question of why 'nobody said anything'. Exploring silences in relation to power suggests that there are multiple and complex ways that constrained communication is produced in the operating room, which are essential to understand in order to improve interprofessional communication and collaboration.     

Lifestyle and dietary factors in the prevention of lethal prostate cancer

The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake.