Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p

Prediction of specificity-determining residues for small-molecule kinase inhibitors

<p>Abstract</p> <p>Background</p> <p>Designing small-molecule kinase inhibitors with desirable selectivity profiles is a major challenge in drug discovery. A high-throughput screen for inhibitors of a given kinase will typically yield many compounds that inhibit more than one kinase. A series of chemical modifications are usually required before a compound exhibits an acceptable selectivity profile. Rationalizing the selectivity profile for a small-molecule inhibitor in terms of the specificity-determining kinase residues for that molecule can be an important step toward the goal of developing selective kinase inhibitors.</p> <p>Results</p> <p>Here we describe S-Filter, a method that combines sequence and structural information to predict specificity-determining residues for a small molecule and its kinase selectivity profile. Analysis was performed on seven selective kinase inhibitors where a structural basis for selectivity is known. S-Filter correctly predicts specificity determinants that were described by independent groups. S-Filter also predicts a number of novel specificity determinants that can often be justified by further structural comparison.</p> <p>Conclusion</p> <p>S-Filter is a valuable tool for analyzing kinase selectivity profiles. The method identifies potential specificity determinants that are not readily apparent, and provokes further investigation at the structural level.</p

Analyzing the Impacts of Off-Road Vehicle (ORV) Trails on Watershed Processes in Wrangell-St. Elias National Park and Preserve, Alaska

Trails created by off-road vehicles (ORV) in boreal lowlands are known to cause local impacts, such as denuded vegetation, soil erosion, and permafrost thaw, but impacts on stream and watershed processes are less certain. In Wrangell-St. Elias National Park and Preserve (WRST), Alaska, ORV trails have caused local resource damage in intermountain lowlands with permafrost soils and abundant wetlands and there is a need to know whether these impacts are more extensive. Comparison of aerial photography from 1957, 1981, and 2004 coupled with ground surveys in 2009 reveal an increase in trail length and number and show an upslope expansion of a trail system around points of stream channel initiation. We hypothesized that these impacts could also cause premature initiation and headward expansion of channels because of lowered soil resistance and greater runoff accumulation as trails migrate upslope. Soil monitoring showed earlier and deeper thaw of the active layer in and adjacent to trails compared to reference sites. Several rainfall-runoff events during the summer of 2009 showed increased and sustained flow accumulation below trail crossings and channel shear forces sufficient to cause headward erosion of silt and peat soils. These observations of trail evolution relative to stream and wetland crossings together with process studies suggest that ORV trails are altering watershed processes. These changes in watershed processes appear to result in increasing drainage density and may also alter downstream flow regimes, water quality, and aquatic habitat. Addressing local land-use disturbances in boreal and arctic parklands with permafrost soils, such as WRST, where responses to climate change may be causing concurrent shifts in watershed processes, represents an important challenge facing resource managers

Tolerance to the Neuron-Specific Paraneoplastic HuD Antigen

Experiments dating back to the 1940's have led to the hypothesis that the brain is an immunologically privileged site, shielding its antigens from immune recognition. The paraneoplastic Hu syndrome provides a powerful paradigm for addressing this hypothesis; it is believed to develop because small cell lung cancers (SCLC) express the neuron-specific Hu protein. This leads to an Hu-specific tumor immune response that can develop into an autoimmune attack against neurons, presumably when immune privilege in the brain is breached. Interestingly, all SCLC express the onconeural HuD antigen, and clinically useful tumor immune responses can be detected in up to 20% of patients, yet the paraneoplastic neurologic syndrome is extremely rare. We found that HuD-specific CD8+ T cells are normally present in the mouse T cell repertoire, but are not expanded upon immunization, although they can be detected after in vitro expansion. In contrast, HuD-specific T cells could be directly activated in HuD null mice, without the need for in vitro expansion. Taken together, these results demonstrate robust tolerance to the neuronal HuD antigen in vivo, and suggest a re-evaluation of the current concept of immune privilege in the brain

A SNAP-Tagged Derivative of HIV-1—A Versatile Tool to Study Virus-Cell Interactions

Fluorescently labeled human immunodeficiency virus (HIV) derivatives, combined with the use of advanced fluorescence microscopy techniques, allow the direct visualization of dynamic events and individual steps in the viral life cycle. HIV proteins tagged with fluorescent proteins (FPs) have been successfully used for live-cell imaging analyses of HIV-cell interactions. However, FPs display limitations with respect to their physicochemical properties, and their maturation kinetics. Furthermore, several independent FP-tagged constructs have to be cloned and characterized in order to obtain spectral variations suitable for multi-color imaging setups. In contrast, the so-called SNAP-tag represents a genetically encoded non-fluorescent tag which mediates specific covalent coupling to fluorescent substrate molecules in a self-labeling reaction. Fusion of the SNAP-tag to the protein of interest allows specific labeling of the fusion protein with a variety of synthetic dyes, thereby offering enhanced flexibility for fluorescence imaging approaches