Safety and Efficacy of Low Blood Pressures Among Patients With Diabetes Subgroup Analyses From the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial)

ObjectivesWe sought to determine whether the blood pressure (BP) levels at which cardiovascular (CV) protection is achieved differ between diabetic and nondiabetic patients from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial).BackgroundGreater absolute benefits of BP reductions have been claimed for diabetic as compared with nondiabetic patients.MethodsA total of 25,584 patients (9,603 diabetic), older than 55 years, at high CV risk were randomized to ramipril, telmisartan, or both and observed for 4.6 years. We pooled the treatment arms to examine the relationships between BP and the primary composite outcome (CV death, nonfatal myocardial infarction or stroke, or hospitalized heart failure) and its components.ResultsThe primary outcome occurred in 1,938 (20.2%) diabetic patients and in 2,276 (14.2%) nondiabetic patients. Compared with nondiabetic patients, diabetic patients had a significantly higher risk for the primary endpoint (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.38 to 1.57) and CV death (HR: 1.56; 95% CI: 1.42 to 1.71); myocardial infarction (HR: 1.30 (95% CI: 1.17 to 1.46); stroke (HR: 1.39; 95% CI: 1.23 to 1.56); and congestive heart failure hospitalization (HR: 2.06; 95% CI: 1.82 to 2.32). The CV risk was significantly higher in diabetic than in nondiabetic patients regardless of the systolic BP changes during treatment. In both diabetic and nondiabetic patients, progressively greater systolic BP reductions were accompanied by reduced risk for the primary outcome only if baseline systolic BP levels ranged from 143 to 155 mm Hg; except for stroke, there was no benefit in fatal or nonfatal CV outcomes by reducing systolic BP below 130 mm Hg.ConclusionsThe relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients over a wide range of baseline and in-treatment BP values although, for the same systolic BP, a higher risk is observed in diabetic patients. (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]; NCT00153101

A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways.

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)--a multikinase inhibitor--encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities

Carotid intima-media thickness for the practicing lipidologist

BACKGROUND: It is well known that cardiovascular disease is the number one killer of men and women in the United States and in many parts of the developed world. However, early detection of atherosclerosis remains a challenging area of research and development. Stress echo and myocardial perfusion studies were not designed to be screening tests and the majority of literature using these tests is in populations with a high probability of disease. It must be emphasized that negative stress echo and stress MPI tests only imply a lack of flow limiting disease; they do not indicate lack of atherosclerotic disease. It is important to remember that when these tests are ''negative,'' the implication is favorable short-term prognosis rather than any implication regarding lack of disease. In contrast, carotid intima-media thickness (CIMT) scanning protocols can detect atherosclerotic disease in early and asymptomatic stages. For a number of reasons reviewed in this article, CIMT may be a more optimal screening and risk-stratifying technology: CIMT directly visualizes vasculature unlike biomarkers such as LDL cholesterol, hsCRP, or PLA2. METHODS: We performed medline searches for original articles and reviews of carotid IMT from 1985 to the present. We particularly emphasized large multi-center epidemiologic studies of the natural history of patients with carotid IMT measurements. CONCLUSION: There is substantial evidence that CIMT is a suitable surrogate for the coronary tree. CIMT is also (along with coronary calcium scoring) recognized by the American Heart Association as a surrogate marker for coronary artery disease. A recent commentary by Stein, et al reviewed the comparison of CIMT to coronary calcium scoring, with favorable findings for CIMT especially in the healthy young and middle-aged populations, as well as women and African American individuals where coronary calcification has more limited utility. Recent findings of the Multi-Ethnic Study of Atherosclerosis indicate further that increased CIMT predicted CVD events in individuals without coronary calcification.

Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109281/1/jcpt12200.pd

A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivatable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with photo-initiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivatable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release whilst reducing systemic drug exposure and associated toxicities