943 research outputs found
Drukte op de HAP door ouders met jonge kinderen [The impact of demand management strategies on parents’ decision-making for out-of-hours primary care: Findings from a survey in the Netherlands]
No full textKeizer E, Giesen MJ, van de Pol J, Knoben J, Wensing M, Giesen
Assessment of five oblique radiographic projections of the canine temporomandibular joint
No full textInvestigation of temporomandibular joint (TMJ) disease requires a clear diagnostic image, which can be challenging to obtain using conventional radiography. The aim of this study was to compare five different oblique radiographic views with the head in lateral recumbency, assessing the clarity of visualization of the normal TMJ anatomy. The views under investigation were the laterorostral–laterocaudal oblique at a 10° and 20° rotation of the head (“nose-up” view), laterorostral–laterocaudal oblique with a rostrocaudal X-ray beam angulation of 10° and 20°, and a parallax view with the beam centered over C2 and collimated to include the TMJ region, using the divergence of the X-ray beam to project the TMJs separately on the radiograph. The views were performed on both TMJs of thirty canine cadavers and were graded independently by experienced and inexperienced observers. Grading was performed on the mandibular fossa, condylar process, joint space, retroarticular process, and the overall TMJ, and was based on a four-point scale. Mean grades for each component and for the overall joint were compared for each observer and each projection. Mean grades were significantly (P < 0.05) higher for the “Nose-up” projections than the angled beam or parallax projections, as was interobserver agreement, and both observers showed significantly higher (P < 0.05) mean grades for the 20o “Nose-up” angulation than the 10o “Nose-up” angulation. These results suggest that a latero 20o rostral–laterocaudal oblique gives the best representation of the anatomy of the TMJ of the dog of the projections assessed, and should be considered when investigating clinical cases of TMJ disease
Tearing down walls: opening the border between hospital and ambulatory care for quality improvement in Germany.
No full textItem does not contain fulltextThe hospital benchmarking system in Germany was originally introduced to detect unintended consequences of reimbursement based on diagnosis-related groups. The new nationwide SQG programme aims to provide information on quality and outcomes of health care provided in hospital, ambulatory specialist and primary care settings, including the healthcare delivery across different sectors. In 2010 the topics for indicator development were cataract surgery, cervical conization, colectoral cancer and percutaneous coronary interventions or coronary angiography. A systematic stepwise modified RAND/UCLA procedure is applied to develop quality indicators in each of these domains. A general framework for data collection is implemented. Benchmarking results are fed back to providers on a regular basis.01 april 201
Cardiovascular risk management, culture and structure of primary care teams.
No full textOutcomes of cardiovascular risk management (CVRM) have improved by the implementation of a wide range of interventions, but further improvement remains possible. To identify new perspectives for improving quality of CVRM, associations were explored between information exchange networks of health care providers and evidence-based CVRM
Efficient recursive dynamics algorithms for operational-space control with application to legged locomotion
No full textThis paper presents new recursive dynamics algorithms that enable operational-space control of floating-base systems to be performed at faster rates. This type of control approach requires the computation of operational-space quantities and suffers from high computational order when these quantities are directly computed through the use of the mass matrix and Jacobian from the joint-space formulation. While many efforts have focused on efficient computation of the operational-space inertia matrix Λ, this paper provides a recursive algorithm to compute all quantities required for floating-base control of a tree-structure mechanism. This includes the first recursive algorithm to compute the dynamically consistent pseudoinverse of the Jacobian J¯ for a tree-structure system. This algorithm is extended to handle arbitrary contact constraints with the ground, which are often found in legged systems, and uses effective ground contact dynamics approximations to retain computational efficiency. The usefulness of the algorithm is demonstrated through application to control of a high-speed quadruped trot in simulation. Our contact-consistent algorithm demonstrates pitch and roll stabilization for a large dog-sized quadruped running at 3.6 m/s without any contact force sensing, and is shown to outperform a simpler Raibert-style posture controller. In addition, the operational-space control approach allows the dynamic effects of the swing legs to be effectively accounted for at this high speed.
J
¯
for a tree-structure system. This algorithm is extended to handle arbitrary contact constraints with the ground, which are often found in legged systems, and uses effective ground contact dynamics approximations to retain computational efficiency. The usefulness of the algorithm is demonstrated through application to control of a high-speed quadruped trot in simulation. Our contact-consistent algorithm demonstrates pitch and roll stabilization for a large dog-sized quadruped running at 3.6 m/s without any contact force sensing, and is shown to outperform a simpler Raibert-style posture controller. In addition, the operational-space control approach allows the dynamic effects of the swing legs to be effectively accounted for at this high speed.National Science Foundation (U.S.) (Graduate Research Fellowship)National Science Foundation (U.S.) (Grant No. CNS-0960061, with subaward to Ohio State University
Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant
No full textBackground: The multifactorial mechanisms associated with radical reductions in HIV-1 reservoirs after allogeneic hematopoietic stem cell transplant (allo-HSCT), including a case of HIV cure, are not fully understood. Objective: To investigate the mechanism of HIV-1 eradication associated with allo-HSCT. Design: Nested case series within the IciStem observational cohort. Setting: Multicenter European study. Participants: 6 HIV-infected, antiretroviral-treated participants who survived more than 2 years after allo-HSCT with CCR5 wildtype donor cells. Measurements: HIV DNA analysis, HIV RNA analysis, and quantitative viral outgrowth assay were performed in blood, and HIV DNA was also measured in lymph nodes, ilea, bone marrow, and cerebrospinal fluid. A humanized mouse model was used for in vivo detection of the replication-competent blood cell reservoir. HIV-specific antibodies were measured in plasma. Results: Analysis of the viral reservoir showed that 5 of 6 participants had full donor chimera in T cells within the first year after transplant, undetectable proviral HIV DNA in blood and tissue, and undetectable replication-competent virus (<0.006 infectious unit per million cells). The only participant with detectable virus received cord blood stem cells with an antithymocyte globulin- containing conditioning regimen, did not develop graft-versushost disease, and had delayed complete standard chimerism in T cells (18 months) with mixed ultrasensitive chimera. Adoptive transfer of peripheral CD4+ T cells to immunosuppressed mice resulted in no viral rebound. HIV antibody levels decreased over time, with 1 case of seroreversion. Limitation: Few participants. Conclusion: Allo-HSCT resulted in a profound long-term reduction in the HIV reservoir. Such factors as stem cell source, conditioning, and a possible "graft-versus-HIV-reservoir" effect may have contributed. Understanding the mechanisms involved in HIV eradication after allo-HSCT can enable design of new curative strategies
Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers
No full textJ Nagelschmitz,1 M Blunck,1 J Kraetzschmar,1 M Ludwig,1 G Wensing,1 T Hohlfeld2 1Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany; 2Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany Background: The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Methods: Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results: A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion: This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing. Keywords: intravenous acetylsalicylic acid, oral acetylsalicylic acid, pharmacodynamics, pharmacokinetics, platelet aggregation, cyclooxygenase-1, thromboxane formatio
Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe
No full textBackground: The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice. Methods: A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch=failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm. Results: Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n=53). In multilevel, multivariate analysis, infection with subtype B (P=0.011), baseline CD4 count <200 cells/mm3 (P<0.001), GSS<3(P=0.002) and use of lamivudine (P<0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS<3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT). Conclusions: In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS<3
The Calculated Genetic Barrier for Antiretroviral Drug Resistance Substitutions Is Largely Similar for Different HIV-1 Subtypes
No full textBACKGROUND:
The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe.
METHODS:
The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype.
RESULTS:
Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes.
CONCLUSIONS:
Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected
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