Results of an international survey on the investigation and endovascular management of cerebral vasospasm and delayed cerebral ischemia

Background: Delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage. Endovascular management of this condition offers a new hope in preventing adverse outcome; however, a uniform standard of practice is lacking owing to a paucity of clinical trials. We conducted an international survey on the use of investigative and endovascular techniques in the treatment of DCI to assess the variability of current practice. Methods: Neurovascular neurosurgeons and neuroradiologists were contacted through professional societies from America, United Kingdom, Europe, and Australasia. Members were invited to complete a 13-item questionnaire regarding screening techniques, first-line and second-line therapies in endovascular intervention, and the role of angioplasty. Answers were compared using χ2 testing for nonparametric data. Results: Data from 344 respondents from 32 countries were analyzed: 167 non-United States and 177 U.S. respondents. More than half of all clinicians had 10+ years of experience in units with a mixture of higher and lower case volumes. Daily transcranial Doppler ultrasonography was the most commonly used screening technique by both U.S. (70%) and non-U.S. (53%) practitioners. Verapamil was the most common first-line therapy in the United States, whereas nimodipine was most popular in non-U.S. countries. Angioplasty was performed by 83% of non-U.S. and 91% of U.S. clinicians in the treatment of vasospasm; however, more U.S. clinicians reported using angioplasty for distal vasospasm. Conclusions: Treatment practices for DCI vary considerably, with the greatest variability in the choice of agent for intra-arterial therapy. Our data demonstrate the wide variation of approaches in use at present. However, without further clinical trials and development of a uniform standard of best practice, variability in treatment and outcome for DCI is likely to continue

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Large head metal-on-metal cementless total hip arthroplasty versus 28mm metal-on-polyethylene cementless total hip arthroplasty: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis of the hip is successfully treated by total hip arthroplasty with metal-on-polyethylene articulation. Polyethylene wear debris can however lead to osteolysis, aseptic loosening and failure of the implant. Large head metal-on-metal total hip arthroplasty may overcome polyethylene wear induced prosthetic failure, but can increase systemic cobalt and chromium ion concentrations. The objective of this study is to compare two cementless total hip arthroplasties: a conventional 28 mm metal-on-polyethylene articulation and a large head metal-on-metal articulation. We hypothesize that the latter arthroplasties show less bone density loss and higher serum metal ion concentrations. We expect equal functional scores, greater range of motion, fewer dislocations, fewer periprosthetic radiolucencies and increased prosthetic survival with the metal-on-metal articulation.</p> <p>Methods</p> <p>A randomized controlled trial will be conducted. Patients to be included suffer from non-inflammatory degenerative joint disease of the hip, are aged between 18 and 80 and are admitted for primary cementless unilateral total hip arthroplasty. Patients in the metal-on-metal group will receive a cementless titanium alloy acetabular component with a cobalt-chromium liner and a cobalt-chromium femoral head varying from 38 to 60 mm. Patients in the metal-on-polyethylene group will receive a cementless titanium alloy acetabular component with a polyethylene liner and a 28 mm cobalt-chromium femoral head. We will assess acetabular bone mineral density by dual energy x-ray absorptiometry (DEXA), serum ion concentrations of cobalt, chromium and titanium, self reported functional status (Oxford hip score), physician reported functional status and range of motion (Harris hip score), number of dislocations and prosthetic survival. Measurements will take place preoperatively, perioperatively, and postoperatively (6 weeks, 1 year, 5 years and 10 years).</p> <p>Discussion</p> <p>Superior results of large head metal-on-metal total hip arthroplasty over conventional hip arthroplasty have been put forward by experts, case series and the industry, but to our knowledge there is no randomized controlled evidence.</p> <p>Conclusion</p> <p>This randomized controlled study has been designed to test whether large head metal-on-metal cementless total hip arthroplasty leads to less periprosthetic bone density loss and higher serum metal ion concentrations compared to 28 mm metal-on-polyethylene cementless total hip arthroplasty.</p> <p>Trial registration</p> <p>Netherlands Trial Registry NTR1399</p

A Guided Workbook Intervention (WorkPlan) to Support Work-Related Goals Among Cancer Survivors: Protocol of a Feasibility Randomized Controlled Trial

Background: Returning to and staying at work following illness is associated with better physical and psychological functioning. Not working has been shown to be associated with reduced self-esteem, lowered self-efficacy, and decreased belief in one's ability to return to the workplace. Although there is a growing body of research looking at what predicts return to work following cancer treatment, there are fewer studies examining interventions targeting return to work. Objective: The primary objective is to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support cancer patients in returning to work to inform a fully powered randomized controlled trial (RCT). Methods: This is a multicenter feasibility RCT where the main analysis uses a qualitative approach. Sixty participants (aged 18-65 years) who have received a diagnosis of cancer and who intend to return to work will be randomized to either the WorkPlan intervention group or a usual care group (ratio 1:1). Participants in the intervention group will receive a guided workbook intervention (which contains activities aimed at eliciting thoughts and beliefs, identifying targets and actions, and concrete steps to achieve goals) and will receive telephone support over a 4-week period. The primary outcome measure is time taken to return to work (in days), and secondary outcome measures include mood, quality of life, illness perceptions, and job satisfaction. Data will be collected through postal questionnaires administered immediately postintervention and at 6- and 12-month follow-ups. In addition, interviews will be undertaken immediately postintervention (to explore acceptability of the intervention and materials) and at 12-month follow-up (to explore perceptions of participation in the trial and experiences of returning to work). Results: Enrollment for the study will be completed in May 2016. Data analysis will commence in April 2017, and the first results are expected to be submitted for publication in late 2017. Conclusions: Currently no standardized return-to-work intervention based on targeting cancer patient beliefs is in existence. If the intervention is shown to be feasible and acceptable, the results of this study will inform a future full RCT with the potential to provide a valuable and cost-efficient tool in supporting cancer survivors in the return-to-work process

Changes in Biomass and Diversity of Soil Macrofauna along a Climatic Gradient in European Boreal Forests

Latitudinal gradients allow insights into the factors that shape ecosystem structure and delimit ecosystem processes, particularly climate. We asked whether the biomass and diversity of soil macrofauna in boreal forests change systematically along a latitudinal gradient spanning from 60° N to 69° N. Invertebrates (3697 individuals) were extracted from 400 soil samples (20 × 20 cm, 30 cm depth) collected at ten sites in 2015–2016 and then weighed and identified. We discovered 265 species living in soil and on the soil surface; their average density was 0.486 g d·w·m−2. The species-level diversity decreased from low to high latitudes. The biomass of soil macrofauna showed no latitudinal changes in early summer but decreased towards the north in late summer. This variation among study sites was associated with the decrease in mean annual temperature by ca 5 °C and with variation in fine root biomass. The biomass of herbivores and fungivores decreased towards the north, whereas the biomass of detritivores and predators showed no significant latitudinal changes. This variation in latitudinal biomass patterns among the soil macrofauna feeding guilds suggests that these guilds may respond differently to climate change, with poorly understood consequences for ecosystem structure and functions

The unexplained success of stentplasty vasospasm treatment

Background Cerebral vasospasm (CVS) following subarachnoid hemorrhage occurs in up to 70% of patients. Recently, stents have been used to successfully treat CVS. This implies that the force required to expand spastic vessels and resolve vasospasm is lower than previously thought. Objective We develop a mechanistic model of the spastic arterial wall to provide insight into CVS and predict the forces required to treat it. Material and Methods The arterial wall is modelled as a cylindrical membrane using a constrained mixture theory that accounts for the mechanical roles of elastin, collagen and vascular smooth muscle cells (VSMC). We model the pressure diameter curve prior to CVS and predict how it changes following CVS. We propose a stretch-based damage criterion for VSMC and evaluate if several commercially available stents are able to resolve vasospasm. Results The model predicts that dilatation of VSMCs beyond a threshold of mechanical failure is sufficient to resolve CVS without damage to the underlying extracellular matrix. Consistent with recent clinical observations, our model predicts that existing stents have the potential to provide sufficient outward force to successfully treat CVS and that success will be dependent on an appropriate match between stent and vessel. Conclusion Mathematical models of CVS can provide insights into biological mechanisms and explore treatment approaches. Improved understanding of the underlying mechanistic processes governing CVS and its mechanical treatment may assist in the development of dedicated stents