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High blood pressure [keywords]
- Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer. [JOURNAL ARTICLE]
- J Clin Oncol 2014 Sep 15.
Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).
- The benefits of breakfast cereal consumption: a systematic review of the evidence base. [Journal Article]
- Adv Nutr 2014 Sep; 5(5):636S-73S.
There have been no comprehensive reviews of the relation of breakfast cereal consumption to nutrition and health. This systematic review of all articles on breakfast cereals to October 2013 in the Scopus and Medline databases identified 232 articles with outcomes related to nutrient intake, weight, diabetes, cardiovascular disease, hypertension, digestive health, dental and mental health, and cognition. Sufficient evidence was available to develop 21 summary evidence statements, ranked from A (can be trusted to guide practice) to D (weak and must be applied with caution). Breakfast cereal consumption is associated with diets higher in vitamins and minerals and lower in fat (grade B) but is not associated with increased intakes of total energy or sodium (grade C) or risk of dental caries (grade B). Most studies on the nutritional impact are cross-sectional, with very few intervention studies, so breakfast cereal consumption may be a marker of an overall healthy lifestyle. Oat-, barley-, or psyllium-based cereals can help lower cholesterol concentrations (grade A), and high-fiber, wheat-based cereals can improve bowel function (grade A). Regular breakfast cereal consumption is associated with a lower body mass index and less risk of being overweight or obese (grade B). Presweetened breakfast cereals do not increase the risk of overweight and obesity in children (grade C). Whole-grain or high-fiber breakfast cereals are associated with a lower risk of diabetes (grade B) and cardiovascular disease (grade C). There is emerging evidence of associations with feelings of greater well-being and a lower risk of hypertension (grade D), but more research is required.
- A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-α Antagonist. [JOURNAL ARTICLE]
- J Rheumatol 2014 Sep 15.
Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-α antagonist.Adult patients were randomized (1:1:1) to fostamatinib [100 mg bid for 24 weeks (n = 105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n = 108; Group B), or to placebo (n = 110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24.Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p = 0.004), but not B (27.8%; p = 0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (≥ 140/90 mm Hg) at ≥ 1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group.Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.
- Rebuttal from markus p. Schlaich, yusuke sata and murray d. Esler. [Journal Article]
- J Physiol 2014 Sep 15; 592(Pt 18):3947.
- CrossTalk opposing view: Which technique for controlling resistant hypertension? Carotid chemoreceptor denervation/modulation. [Journal Article]
- J Physiol 2014 Sep 15; 592(Pt 18):3941-4.
- CrossTalk opposing view: Which technique for controlling resistant hypertension? Renal nerve ablation. [Journal Article]
- J Physiol 2014 Sep 15; 592(Pt 18):3937-40.
- CrossTalk opposing view: Which technique for controlling resistant hypertension? Carotid sinus stimulation. [Journal Article]
- J Physiol 2014 Sep 15; 592(Pt 18):3933-5.
- Endothelial Dysfunction Plays a Key Role in Increasing Cardiovascular Risk in Type 2 Diabetes: The Hoorn Study. [JOURNAL ARTICLE]
- Hypertension 2014 Sep 15.
In the pathogenesis of cardiovascular events, interaction between risk factors has seldom been identified. However, endothelial dysfunction on the one hand and type 2 diabetes mellitus, impaired glucose metabolism (IGM), and insulin resistance on the other may act synergistically (ie, interact) in the development of cardiovascular disease. We therefore investigated the interaction between endothelial dysfunction and type 2 diabetes mellitus, IGM, and insulin resistance with regard to risk of cardiovascular events. In a prospective population-based cohort (n=445; 69 years; 55% women; 23% type 2 diabetes mellitus, 28% IGM [by design]), endothelial dysfunction (brachial artery flow-mediated dilatation), glucose tolerance (oral glucose tolerance test), and insulin sensitivity (homeostasis model assessment for insulin resistance [HOMA2-IR]) were determined. After a median follow-up of 7.6 years, 106 participants had had a cardiovascular event. After adjustments, 1 SD less flow-mediated dilatation was associated with cardiovascular events in type 2 diabetes mellitus (hazard ratio 1.69 [95% confidence interval, 1.14-2.52]) and IGM (1.50 [0.95-2.37]) and among those in the highest HOMA2-IR tertile (1.92 [1.42-2.60]), but not in normal glucose metabolism (0.85 [0.63-1.16]) or among those in the lower 2 HOMA2-IR tertiles combined (0.85 [0.65-1.12]). Interaction between flow-mediated dilatation and type 2 diabetes mellitus, IGM, or insulin resistance was present on an additive (relative excess risk caused by interaction >0) and on a multiplicative scale (P interaction <0.05). Endothelial dysfunction and type 2 diabetes mellitus, IGM, or insulin resistance synergistically increase cardiovascular event risk. This identifies endothelial dysfunction as a key therapeutic target in these individuals.
- Longitudinal Perspective on the Conundrum of Central Arterial Stiffness, Blood Pressure, and Aging. [JOURNAL ARTICLE]
- Hypertension 2014 Sep 15.
The age-associated increase in arterial stiffness has long been considered to parallel or to cause the age-associated increase in blood pressure (BP). Yet, the rates at which pulse wave velocity (PWV), a measure of arterial stiffness, and BP trajectories change over time within individuals who differ by age and sex have not been assessed and compared. This study determined the evolution of BP and aortic PWV trajectories during a 9.4-year follow-up in >4000 community-dwelling men and women of 20 to 100 years of age at entry into the SardiNIA Study. Linear mixed effects model analyses revealed that PWV accelerates with time during the observation period, at about the same rate over the entire age range in both men and women. In men, the longitudinal rate at which BP changed over time, however, did not generally parallel that of PWV acceleration: at ages >40 years the rates of change in systolic BP (SBP) and pulse pressure (PP) increase plateaued and then declined so that SBP, itself, also declined at older ages, whereas PP plateaued. In women, SBP, diastolic BP, and mean BP increased at constant rates across all ages, producing an increasing rate of increase in PP. Therefore, increased aortic stiffness is implicated in the age-associated increase in SBP and PP. These findings indicate that PWV is not a surrogate for BP and that arterial properties other than arterial wall stiffness that vary by age and sex also modulate the BP trajectories during aging and lead to the dissociation of PWV, PP, and SBP trajectories in men.