Purpose
Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line ...aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit.
Experimental design
Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points.
Results
Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3–38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4–43.7%) by per-protocol analysis. In those patients that achieved clinical benefit (
n
= 5), the median (interquartile range) duration was 9.4 months (8.1–11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5–4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%).
Conclusions
The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments.
Sensing and cognition by homeowners and technicians for home maintenance are prime examples of human–building interaction. Damage, decay, and pest infestation present signals that humans interpret ...and then act upon to remedy and mitigate. The maintenance cognition process has direct effects on sustainability and economic vitality, as well as the health and well-being of building occupants. While home maintenance practices date back to antiquity, they readily submit to augmentation and improvement with modern technologies. This paper describes the use of networked smart technologies embedded with machine learning (ML) and presented in electronic formats to better inform homeowners and occupants about safety and maintenance issues, as well as recommend courses of remedial action. The demonstrated technologies include robotic sensing in confined areas, LiDAR scans of structural shape and deformation, moisture and gas sensing, water leak detection, network embedded ML, and augmented reality interfaces with multi-user teaming capabilities. The sensor information passes through a private local dynamic network to processors with neural network pattern recognition capabilities to abstract the information, which then feeds to humans through augmented reality and conventional smart device interfaces. This networked sensor system serves as a testbed and demonstrator for home maintenance technologies, for what can be termed Home Maintenance 4.0.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Fibromyalgia has previously been categorized as primary, secondary, and juvenile fibromyalgia. However, these definitions do not adequately explain the etiopathology of disease, nor do they help ...direct new specific therapies. Herein, we review the previously known categorizations of fibromyalgia. Based on common patient characteristics and previously studied pathophysiologies, we propose new subcategorizations of fibromyalgia that we have self-narrated, including hormonal fibromyalgia, neuroendocrine fibromyalgia, psychologic fibromyalgia, inflammatory fibromyalgia, and lastly, neuropathic fibromyalgia. Future research needs to be done to verify, add to, and fully describe these self-narrated categories of fibromyalgia that we have proposed.
In the original publication of the article, a part of acknowledgement section was missed out. The omitted acknowledgement is given below: ‘The study was coordinated by the Imperial Clinical Trials ...Unit—Cancer, Imperial College London and Sponsored by Imperial College London. The Imperial Clinical Trials Unit receives funding from the National Institute for Health (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This study was supported by Imperial Experimental Cancer Medicine Centre and Cancer Research UK Imperial Centre’.
Recent evidence has shown that clopidogrel and proton pump inhibitors (PPIs) are metabolized by the same pathway and that patients taking both drugs have greater levels of platelet reactivity and ...more adverse outcomes than patients taking only clopidogrel. We sought to examine the effect of a PPI at discharge from the hospital after percutaneous coronary intervention with drug-eluting stents on the incidence of major adverse cardiac events (MACE) at 1 year. We compared 502 patients who were not prescribed a PPI at discharge and 318 patients who were prescribed a PPI. All patients were taking clopidogrel. We followed patients for 1 year with regard to MACE, including death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. We performed multivariate Cox regression to adjust for confounding variables, including compliance with clopidogrel, to assess the effect of a PPI at discharge on the 1-year outcomes. The baseline characteristics of patients discharged with a PPI were similar to those of patients discharged without a PPI. Univariate survival analysis of the outcomes showed a greater rate of MACE (13.8% vs 8.0%, p = 0.008) and overall mortality (4.7% vs 1.8%, p = 0.02) in the PPI group. After multivariate analysis, the adjusted MACE hazard ratio for PPI at discharge was 1.8 (95% confidence interval 1.1 to 2.7, p = 0.01). In conclusion, in patients undergoing percutaneous coronary intervention with drug-eluting stents and receiving clopidogrel, the prescription of a PPI at discharge was associated with a greater rate of MACE at 1 year.
Performance of percutaneous coronary intervention (PCI) at centers without cardiothoracic surgery is a contentious issue. Although this practice allows greater access to care, there are safety ...concerns. The aim was to assess the requirement for emergent coronary artery bypass grafting (CABG) after PCI and characterize patients at highest risk using independent predictors. The study population consisted of 21,957 unselected patients who underwent PCI from August 1994 (Food and Drug Administration stent approval) to January 2008 at a single medical center. Patients requiring emergent CABG (defined as within 24 hours of the index procedure) were identified. Logistic regression analysis was performed to assess for independent correlates of emergent CABG. Emergent CABG was required in 90 patients (cumulative incidence 0.41%). Indications for CABG included triple-vessel disease, dissection, acute closure, perforation, and failure to cross. These patients had significantly higher in-hospital cardiac death rates (7.8% vs 0.7%; p <0.01) and higher rates of Q-wave myocardial infarction, neurologic events, and renal insufficiency. Independent correlates of emergent CABG after PCI were acute ST-segment elevation myocardial infarction presentation, cardiogenic shock, triple-vessel disease, and type C lesion. Risk assessment based on these predictors identified 0.3% of the patient population to have a 9.3% cumulative incidence of emergent CABG. In conclusion, the need for emergent CABG after PCI in the stent era was low and was associated with poor in-hospital outcomes. Risk was nonuniform, with 0.3% of the study population, characterized by acute presentation and complex coronary disease, at heightened risk of emergent surgery.
Transcatheter aortic valve implantation (TAVI) without replacement requires precise knowledge of the anatomic dimensions and physical characteristics of the peripheral vasculature and aortic valve ...annulus at the insertion of the aortic valve leaflet and root at the level of the sinus of Valsalva. Multislice computed tomography (CT) allows detailed and precise assessment of the anatomic variables. Noncardiovascular structures are also amenable to assessment by CT. Of the 394 patients screened for TAVI, 259 (65.7%) had non-contrast CT to evaluate chest anatomy and contrast CT to evaluate ilio-femoral anatomy. Significant noncardiac findings were defined as those requiring immediate evaluation or intervention or additional clinical or radiologic follow-up. Noncardiovascular findings known before CT were not included. Of the 259 patients, 105 (40.5%) were men. The mean age was 82.3 ± 8.1 years. New, significant noncardiovascular findings were found in 89 (34.3%) and malignancy in 11 (4.2%) patients. Insignificant noncardiovascular findings were identified in 222 patients (85.7%). Signs of fluid retention were noted on CT in 105 patients (40.5%), with pleural effusion in 100 (38.6%), ascites in 17 (6.5%), and pericardial effusion in 14 (5.4%). Important peripheral vascular disease was found in 98 patients (37.8%), resulting in exclusion of 49 (19.1%) from TAVI using the transfemoral approach. An aortic aneurysm was found in 10 patients (3.8%) and a “porcelain” aorta (heavily calcified ascending aorta) in 19 (7.3%). In conclusion, malignancy and other noncardiovascular abnormalities are often found in patients who undergo CT for evaluation for TAVI. Populations must be meticulously examined to ensure that important findings are not missed.
The Registry Experience at the Washington Hospital Center with Drug-Eluting Stents (REWARDS) study includes unselected patients with coronary artery disease treated with sirolimus-eluting stents ...(SESs; n = 2,392) or paclitaxel-eluting stents (PES; n = 1,119). This study aimed to examine the long-term safety profile of the 2 stents in a “real-world” population, especially in relation to stent thrombosis, and to compare differences in the diabetic cohort. Patients were followed for 3 years with regard to major adverse cardiac events (MACEs), including death, Q-wave myocardial infarction, and target lesion revascularization. Rates of stent thrombosis were also studied. Baseline characteristics were similar between stents. Although MACE rates at 3 years were similar (SES 28.1% vs PES 28.9%, p = 0.62), there was a significant difference in unadjusted rates of target lesion revascularization (SES 15.6% vs PES 12.6%, p = 0.03), death (SES 15.7% vs PES 19.0%, p = 0.02), and Q-wave myocardial infarction (SES 0.8% vs PES 2.1%, p = 0.003). After multivariable Cox regression to adjust for confounders, there was no significant difference in overall MACEs. Incidence of stent thrombosis was higher in the SES group (SES 2.2% vs PES 1.6%, p = 0.22), but this was not statistically significant (hazard ratio 1.6, 95% confidence interval 0.8 to 2.9, p = 0.17). Overall, diabetics had a higher MACE rate, but there was no difference between insulin- and noninsulin-dependent diabetics. In conclusion, at 3 years, PES and SES achieved similar results in MACEs and stent thrombosis. This should foster confidence that SES or PES can be compared to second-generation drug-eluting stents without concerns for safety or efficacy.
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