Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER

AbstractBackgroundGuidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments.MethodsData from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin.ResultsEach dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C < 100 mg/dL and non-HDL-C < 130 mg/dL than the same or double dose of atorvastatin; atorvastatin 80 mg was significantly superior to rosuvastatin 10 mg (all p < 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p < 0.001), except for rosuvastatin 10 mg versus simvastatin 80 mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C < 70 mg/dL and non-HDL-C < 100 mg/dL than the same or double dose of atorvastatin (all p < 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p ≤ 0.020), except for rosuvastatin 10 mg versus simvastatin 40 mg and 80 mg (non-significant).ConclusionsPhysicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines

Effects of dalcetrapib in patients with a recent acute coronary syndrome

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes

Sprinting with an amputation: Some race-based lower-limb step observations.

BACKGROUND: T44 sprinting with an amputation is still in a state of relative infancy. Future scope for athletic training and prosthetic limb development may be assisted with a better understanding of information derived from T44 athletes when under race-based conditions. OBJECTIVES: To investigate the behaviour of step count and step frequency when under competitive conditions. STUDY DESIGN: The study comprises two elements: (1) a video-based analysis of race-based limb-to-limb symmetry and (2) a video-based analysis of race-based step count. METHODS: Video analysis of several major events from 1996-2012 are assessed for step count and step limb-to-limb symmetry characteristics. RESULTS: The video analysis highlights limb-to-limb imbalances greater than those indicated in the previous literature. A low step count is determined to be desirable for success in the 100-m event. CONCLUSION: Future analysis of athletes with a lower-limb amputation would be worthwhile when placed under race-based conditions as the limb-to-limb behaviour is more exaggerated than those seen in typical studies held within a laboratory setting. The within-event behaviour of step counts requires further investigation to establish where these take place or whether it is a cumulative step length issue. CLINICAL RELEVANCE: This article increases the understanding of the race-based behaviour of amputee athletes and provides more information to contribute to any discussions on the performance of lower-limb prostheses

The Reliability of Global and Hemispheric Surface Temperature Records

The purpose of this review article is to discuss the development and associated estimation of uncertainties in the global and hemispheric surface temperature records. The review begins by detailing the groups that produce surface temperature datasets. After discussing the reasons for similarities and differences between the various products, the main issues that must be addressed when deriving accurate estimates, particularly for hemispheric and global averages, are then considered. These issues are discussed in the order of their importance for temperature records at these spatial scales: biases in SST data, particularly before the 1940s; the exposure of land-based thermometers before the development of louvred screens in the late 19th century; and urbanization effects in some regions in recent decades. The homogeneity of land-based records is also discussed; however, at these large scales it is relatively unimportant. The article concludes by illustrating hemispheric and global temperature records from the four groups that produce series in near-real time

Short‐term recovery trajectories of acute flares in knee pain: a UK‐Netherlands multi‐centre prospective cohort analysis

Objective To identify distinct recovery trajectories of acute flares of knee pain and associated participant characteristics. Methods Data were from the FLARE randomized controlled trial, a multicenter trial in 27 primary care centers in the UK and Netherlands of 3 regimes of oral nonsteroidal antiinflammatory therapy for acute flares of knee pain. Individuals with a history of inflammatory/crystal arthritis, fibromyalgia, and chronic pain syndrome were excluded. Latent class growth analysis was applied to measures of pain intensity repeated over 5 days to identify distinct recovery trajectories. The concurrent courses of interference with activity, stiffness, and swelling for each trajectory group were modelled using generalized estimating equations. Participant age, sex, obesity, and osteoarthritis diagnosis were described for each trajectory group. Results A total of 449 participants were included (median age 55 years, 41% female, 35% obese, and 42% diagnosed with osteoarthritis). A 6‐group cubic model was deemed optimal, with trajectories distinguished by rate of pain reduction and absolute level at final measurement. At the extremes were rapid and near‐complete resolution (n = 41, 9%) and persistent, high pain (n = 25, 6%), but most participants showed a reduction and plateau in pain severity within 3–5 days. Within each pain trajectory group, interference with activity, stiffness, and swelling followed the same course as pain. Baseline characteristics did not differ substantially between trajectory groups. Conclusion Even under a well‐adhered to regime of oral nonsteroidal antiinflammatory medication, recovery following acute flares of knee pain is heterogeneous. Our observations that favorable trajectories are apparent within 3–5 days can help to inform treatment decision‐making in the patient–health care professional consultation

The biophysical climate mitigation potential of boreal peatlands during the growing season

Peatlands and forests cover large areas of the boreal biome and are critical for global climate regulation. They also regulate regional climate through heat and water vapour exchange with the atmosphere. Understanding how land-atmosphere interactions in peatlands differ from forests may therefore be crucial for modelling boreal climate system dynamics and for assessing climate benefits of peatland conservation and restoration. To assess the biophysical impacts of peatlands and forests on peak growing season air temperature and humidity, we analysed surface energy fluxes and albedo from 35 peatlands and 37 evergreen needleleaf forests-the dominant boreal forest type-and simulated air temperature and vapour pressure deficit (VPD) over hypothetical homogeneous peatland and forest landscapes. We ran an evapotranspiration model using land surface parameters derived from energy flux observations and coupled an analytical solution for the surface energy balance to an atmospheric boundary layer (ABL) model. We found that peatlands, compared to forests, are characterized by higher growing season albedo, lower aerodynamic conductance, and higher surface conductance for an equivalent VPD. This combination of peatland surface properties results in a similar to 20% decrease in afternoon ABL height, a cooling (from 1.7 to 2.5 degrees C) in afternoon air temperatures, and a decrease in afternoon VPD (from 0.4 to 0.7 kPa) for peatland landscapes compared to forest landscapes. These biophysical climate impacts of peatlands are most pronounced at lower latitudes (similar to 45 degrees N) and decrease toward the northern limit of the boreal biome (similar to 70 degrees N). Thus, boreal peatlands have the potential to mitigate the effect of regional climate warming during the growing season. The biophysical climate mitigation potential of peatlands needs to be accounted for when projecting the future climate of the boreal biome, when assessing the climate benefits of conserving pristine boreal peatlands, and when restoring peatlands that have experienced peatland drainage and mining.Peer reviewe

Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age???18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or??2 of the following: age???65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365?days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue