Demonstration of inferior vena cava compression by probe pressure during subxiphoid echocardiography

We sought to compare the inferior vena cava diameter measured by transthoracic echocardiography and by transesophageal echocardiography in human and animals. Transthoracic echocardiography yielded lower inferior vena cava diameter values than transesophageal echocardiography. Adult and pediatric intensivists should pay attention to the risk of false measurement of the inferior vena cava anterior-posterior diameter that may be due to compression of the inferior vena cava by the sonographic probe when the subxiphoid view is used.     

Multimodal assessment of early tumor response to chemotherapy: comparison between diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles targeted at cell death

The aim of this study was to determine the value of different magnetic resonance (MR) protocols to assess early tumor response to chemotherapy. We used a murine tumor model (TLT) presenting different degrees of response to three different cytotoxic agents. As shown in survival curves, cyclophosphamide (CP) was the most efficient drug followed by 5-fluorouracil (5-FU), whereas the etoposide treatment had little impact on TLT tumors. Three different MR protocols were used at 9.4 Tesla 24 h post-treatment: diffusion-weighted (DW)-MRI, choline measurement by (1) H MRS, and contrast-enhanced MRI using ultrasmall iron oxide nanoparticles (USPIO) targeted at phosphatidylserine. Accumulation of contrast agent in apoptotic tumors was monitored by T(2) -weighted images and quantified by EPR spectroscopy. Necrosis and apoptosis were assessed by histology. Large variations were observed in the measurement of choline peak areas and could not be directly correlated to tumor response. Although the targeted USPIO particles were able to significantly differentiate between the efficiency of each cytotoxic agent and best correlated with survival endpoint, they present the main disadvantage of non-specific tumor accumulation, which could be problematic when transferring the method to the clinic. DW-MRI presents a better compromise by combining longitudinal studies with a high dynamic range; however, DW-MRI was unable to show any significant effect for 5-FU. This study illustrates the need for multimodal imaging in assessing tumor response to treatment to compensate for individual limitations.     

The effect of changes in lower limb pain on the rate of progression of locomotor disability in middle and old age: evidence from the NorStOP cohort with 6-year follow-up

Locomotor disability (LMD) is common at older ages, and can lead to other significant disability and mortality. Prevalent pain has been shown to be associated with LMD. This article aimed to assess the association between changes in lower limb pain status (ascertained from a manikin) and changes in the level of self-reported LMD in a sample of UK adults age ≥ 50years, over a 6-year period (data collected at 3-year intervals). There was an average increase in the level of LMD over 6 years. Reports of an onset of lower limb pain were associated with a relative increase in LMD, independently of sociodemographic factors and the onset of selected comorbid diseases. A dose-response relationship was observed between the onset of multiple lower limb joint involvement and more frequent or intense pain and larger increases in LMD. Becoming free from lower limb pain was associated with a relative decrease in LMD, but did not return LMD scores to the level of those who had remained pain-free throughout. This is consistent with a cumulative effect on LMD of recurrent episodes of pain. Lower limb pain may be a key target for prevention and rehabilitation to reduce years lived with disability in later life.     

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro-in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C (max) acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).     

Secondary prevention of ischaemic stroke

Recent trials within the past few years have influenced not only how we treat patients immediately after acute ischaemic stroke, but also how we investigate for aetiology. With the advent of improved medications, procedures and monitoring devices, modern stroke prevention strategies are more individualised, but the decision‐making process is more complex. We provide an approach to navigating these management options.     

Examining management and research priorities in patients with polymyalgia rheumatica: a primary care questionnaire survey

Clinical Rheumatology - Polymyalgia rheumatica (PMR) is a common inflammatory disorder that is usually managed with oral glucocorticoids, which although effective can cause significant adverse...