The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.

Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.

BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. METHODS: The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. RESULTS: The proportion of patients at high risk of CVD increased from 35.3% during 1999-2000 to 41.3% during 2005-2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999-2000], 0.73 cases per 100 PY [95% CI, 0.50-1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44-0.94 cases per 100 PY]; in 2005-2006, 0.36 cases per 100 PY [95% CI, 0.24-0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999-2000], 1.06 cases per 100 PY [95% CI, 0.63-1.77 cases per 100 PY]; in 2004, 1.02 cases per 100 PY [95% CI, 0.61-1.71 cases per 100 PY]; in 2005-2006, 0.63 cases per 100 PY [95% CI, 0.36-1.09 cases per 100 PY]). CONCLUSIONS: Although the CVD risk profile among patients in the Data Collection on Adverse Events of Anti-HIV Drugs Study has decreased since 1999, rates have remained relatively stable, possibly as a result of a more aggressive approach towards managing the risk of CVD.

Biomass production and phosphorus use of forage grasses fertilized with two phosphorus sources

A major constraint to agricultural production in acid soils of tropical regions is the low soil P availability, due to the high adsorption capacity, low P level in the source material and low efficiency of P uptake and use by most of the modern varieties grown commercially. This study was carried out to evaluate the biomass production and P use by forage grasses on two soils fertilized with two P sources of different solubility. Two experiments were carried out, one for each soil (Cambisol and Latosol), using pots filled with 4 dm³ soil in a completely randomized design and a 4 x 2 factorial scheme. The treatments consisted of a combination of four forage plants (Brachiaria decumbens, Brachiaria brizantha, Pennisetum glaucum and Sorghum bicolor) with two P sources (Triple Superphosphate - TSP and Arad Reactive Phosphate - ARP), with four replications. The forage grasses were harvested at pre-flowering, when dry matter weight and P concentrations were measured. Based on the P concentration and dry matter production, the total P accumulation was calculated. With these data, the following indices were calculated: the P uptake efficiency of roots, P use efficiency, use efficiency of available P, use efficiency of applied P and agronomic efficiency. The use of the source with higher solubility (TSP) resulted, generally, in higher total dry matter and total P accumulation in the forage grasses, in both soils. For the less reactive source (ARP), the means found in the forage grasses, for use efficiency and efficient use of available P, were always higher when grown in Latosol, indicating favorable conditions for the solubility of ARP. The total dry matter of Brachiaria brizantha was generally higher, with low P uptake, accumulation and translocation, which indicated good P use efficiency for both P sources and soils. The forage plants differed in the P use potential, due to the sources of the applied P and of the soils used. Less than 10 % of the applied P was immobilized in the forage dry matter. Highest values were observed for TSP, but this was not reflected in a higher use efficiency of P from this source.

Use of human MAR elements to improve retroviral vector production.

Retroviral vectors have many favorable properties for gene therapies, but their use remains limited by safety concerns and/or by relatively lower titers for some of the safer self-inactivating (SIN) derivatives. In this study, we evaluated whether increased production of SIN retroviral vectors can be achieved from the use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of human origin were found to increase and to stabilize the expression of the green fluorescent protein transgene in stably transfected HEK-293 packaging cells. Introduction of one of these MAR elements in retroviral vector-producing plasmids yielded higher expression of the viral vector RNA. Consistently, viral titers obtained from transient transfection of MAR-containing plasmids were increased up to sixfold as compared with the parental construct, when evaluated in different packaging cell systems and transfection conditions. Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors.

Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy

Paul Ehrlich's inspired concept of 'magic bullets' for the cure of diseases has been revitalized by recent advances in immunology1. In particular, the development of cell fusion technology allowing the production of monoclonal antibodies (Mabs) with exquisite specificities2 triggered new hopes that we may now have the perfect carrier molecules with which to deliver cytotoxic drugs3 or toxins4 to the hidden cancer cells. This article reviews data on one aspect of the magic bullet concept, the use of radiolabelled antibodies as tracers for tumour localization. It will also discuss the very recent clinical use of 131I-labelled Mabs against carcinoembryonic antigen (CEA)5 to detect carcinoma either by conventional external photoscanning or by single photon emission computerized tomography (SPELT). This alliance of the most modern tools from immunology (Mabs) and nuclear medicine (SPELT) appears promising as a way to improve the sensitivity of 'immunoscintigraphy'. However, this approach is not yet ready, for widespread clinical use.

The use of total luminescence spectroscopy in the investigation of the effects of different rice management practices on humic substances of a planosol

In the Earth's carbon cycle, C stocks in the soil are higher than in vegetation and atmosphere. Maintaining and conserving organic C concentrations in the soil by specific management practices can improve soil fertility and productivity. The aim of this study was to evaluate the impact of agricultural management techniques and influence of water regime (flooded or drained) on the structure of humic substances by excitation/emission matrix fluorescence. Six samples of a Planosol (Planossolo by the Brazilian System of Soil Classification) were collected from a rice field. Humic substances (HS) were extracted from flooded and drained soil under different agricultural management techniques: conventional tillage, reduced tillage and grassland. Two peaks at a long emission wavelength were observed in the EEM spectra of HA whereas those of the corresponding FA contained a unique fluorophore at an intermediate excitation/emission wavelength pair (EEWP) value. The fluorescence intensity measured by total luminescence (FI TL) of HA was lower than that of the corresponding FA. A comparison of all samples (i.e., the HA values compared to each other) revealed only slight differences in the EEWP position, but the FI TL values were significantly different. In this soil, anoxic conditions and reduced tillage (little plowing) seem to favor a higher degree of humification of the soil organic matter compared with aerated conditions and conventional tillage.

On the use of IRMS in forensic science: proposals for a methodological approach

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensic science denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstrated its potential to distinguish chemically identical compounds coming from different sources. Despite the numerous applications of IRMS to a wide range of forensic materials, its implementation in a forensic framework is less straightforward than it appears. In addition, each laboratory has developed its own strategy of analysis on calibration, sequence design, standards utilisation and data treatment without a clear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose a methodological framework of the whole process using IRMS methods. We emphasize the importance of considering isotopic results as part of a whole approach, when applying this technology to a particular forensic issue. The process is divided into six different steps, which should be considered for a thoughtful and relevant application. The dissection of this process into fundamental steps, further detailed, enables a better understanding of the essential, though not exhaustive, factors that have to be considered in order to obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratory comparisons.

Changes in the use of broad-spectrum antibiotics after withdrawal of cefepime from the market: an interrupted time series analysis

Background and objective: Cefepime was one of the most used broad-spectrum antibiotics in Swiss public acute care hospitals. The drug was withdrawn from market in January 2007, and then replaced by a generic since October 2007. The goal of the study was to evaluate changes in the use of broad-spectrum antibiotics after the withdrawal of the cefepime original product. Design: A generalized regression-based interrupted time series model incorporating autocorrelated errors assessed how much the withdrawal changed the monthly use of other broad-spectrum antibiotics (ceftazidime, imipenem/cilastin, meropenem, piperacillin/ tazobactam) in defined daily doses (DDD)/100 bed-days from January 2004 to December 2008 [1, 2]. Setting: 10 Swiss public acute care hospitals (7 with\200 beds, 3 with 200-500 beds). Nine hospitals (group A) had a shortage of cefepime and 1 hospital had no shortage thanks to importation of cefepime from abroad. Main outcome measures: Underlying trend of use before the withdrawal, and changes in the level and in the trend of use after the withdrawal. Results: Before the withdrawal, the average estimated underlying trend (coefficient b1) for cefepime was decreasing by -0.047 (95% CI -0.086, -0.009) DDD/100 bed-days per month and was significant in three hospitals (group A, P\0.01). Cefepime withdrawal was associated with a significant increase in level of use (b2) of piperacillin/tazobactam and imipenem/cilastin in, respectively, one and five hospitals from group A. After the withdrawal, the average estimated trend (b3) was greatest for piperacillin/tazobactam (+0.043 DDD/100 bed-days per month; 95% CI -0.001, 0.089) and was significant in four hospitals from group A (P\0.05). The hospital without drug shortage showed no significant change in the trend and the level of use. The hypothesis of seasonality was rejected in all hospitals. Conclusions: The decreased use of cefepime already observed before its withdrawal from the market could be explained by pre-existing difficulty in drug supply. The withdrawal of cefepime resulted in change in level for piperacillin/tazobactam and imipenem/cilastin. Moreover, an increase in trend was found for piperacillin/tazobactam thereafter. As these changes generally occur at the price of lower bacterial susceptibility, a manufacturers' commitment to avoid shortages in the supply of their products would be important. As perspectives, we will measure the impact of the changes in cost and sensitivity rates of these antibiotics.

The use of the vac in complex wounds - does it work and how?

Background: Complex wounds pose a major challenge in reconstructive and trauma surgery. Several approaches to increase the healing process have been proposed in the last decades. In this study we study the mechanism of action of the Vacuum Assisted Closure device in diabetic wounds. Methods: Full-thickness wounds were excised in diabetic mice and treated with the VAC device or its isolated components: an occlusive dressing (OD) alone, subathmospheric pressure at 125 mm Hg (Suction), and a polyurethane foam without (Foam) and with (Foamc) downward compression of approximately 125 mm Hg. The last goups were treated with either the complete VAC device (VAC) or with a silicne interface that alows fluid removel (Mepithel-VAC). The effects of the treatment modes on the wound surface were quantified by a two-dimensional immunohistochemical staging system based on vasculature, as defined by blood vessel density (CD31) and cell proliferation (defined by ki67 positivity), 7 days post wounding. Finite element modelling was used to predict wound surface deformation under dressing modes and cross sections of in situ fixed tissues were used to measure actual microstrain. Results: The foam-wound interface of the Vacuum Assisted Closure device causes significant wound stains (60%) causing a deformation of the single cell level leading to a profound upregulation of cell proliferation (4-fold) and angiogenisis (2.2-fold) compared to OD treated wounds. Polyurethane foam exposure itself causes a frather unspecific angiogenic response (Foamc, 2 - fold, Foam, 2.2 - fold) without changes of the cell proliferation rate of the wound bed. Suction alone without a specific interface does not have an effect on meassured parameters, showing similar results to untreated wounds. A perforated silicone interface caused a significant lower microdeforamtion of the wound bed correlating to changes of the wound tissues. Conclusion: The Vacuum Assisted Closure device induce significanttissue growth in diabetic wounds. The wound foam interface under suction causes profound macrodeformation that stimulates tissue growth by angiogenesis and cell proliferation. It needs to be taken in consideration that in the clinical setting different wound types may profit from different elements of this suction device.

The combined use of reflectance, emissivity and elevation Aster/Terra data for tropical soil studies

Reflectance, emissivity and elevation data of the sensor ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer)/Terra were used to characterize soil composition variations according to the toposequence position. Normalized data of SWIR (shortwave infrared) reflectance and TIR (thermal infrared) emissivity, coupled to a soil-fraction image from a spectral mixture model, were evaluated to separate bare soils from nonphotosynthetic vegetation. Regression relationships of some soil properties with reflectance and emissivity data were then applied on the exposed soil pixels. The resulting estimated values were plotted on the ASTER-derived digital elevation model. Results showed that the SWIR bands 5 and 6 and the TIR bands 10 and 14 measured the clay mineral absorption band and the quartz emissivity feature, respectively. These bands improved also the discrimination between nonphotosynthetic vegetation and soils. Despite the differences in pixel size and field sampling size, some soil properties were correlated with reflectance (R² of 0.65 for Al2O3 in band 6; 0.61 for Fe2O3 in band 3) and emissivity (R² of 0.65 for total sand fraction in the 10/14 band ratio). The combined use of reflectance, emissivity and elevation data revealed variations in soil composition with topography in specific parts of the landscape. From higher to lower slope positions, a general decrease in Al2O3 and increase in total sand fraction was observed, due to the prevalence of Rhodic Acrustox at the top and its gradual transition to Typic Acrustox at the bottom.