Conservative treatment in patients with an acute lumbosacral radicular syndrome: design of a randomised clinical trial [ISRCTN68857256]

BACKGROUND: The objective is to present the design of randomised clinical trial (RCT) on the effectiveness of physical therapy added to general practitioners management compared to general practitioners management only in patients with an acute lumbosacral radicular syndrome (also called sciatica). METHODS/DESIGN: Patients in general practice diagnosed with an acute (less than 6 weeks) lumbosacral radicular syndrome and an age above 18 years are eligible for participation. The general practitioners treatment follows their clinical guideline. The physical therapy treatment will consist of patient education and exercise therapy. The primary outcome measure is patients reported global perceived effect. Secondary outcome measures are severity of complaints, functional status, health status, fear of movement, medical consumption, sickness absence, costs and treatment preference. The follow-up is 52 weeks. DISCUSSION: Treatment by general practitioners and physical therapists in this study will be transparent and not a complete "black box". The results of this trial will contribute to the decision of the general practitioner regarding referral to physical therapy in patients with an acute lumbosacral radicular syndrome

Development of an international standard set of value-based outcome measures for patients with chronic kidney disease : a report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD working group

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care

Modulation of Mouse Coagulation Gene Transcription following Acute In Vivo Delivery of Synthetic Small Interfering RNAs Targeting HNF4α and C/EBPα

Hepatocyte nuclear factor 4α (HNF4α) and CCAAT/enhancer-binding protein α (C/EBPα) are important for the transcriptional control of coagulation factors. To determine in vivo the direct role of HNF4α and C/EBPα in control of genes encoding coagulation factors, a synthetic small interfering (si)RNA approach was used that enabled strong reduction of mouse hepatic HNF4α and C/EBPα under conditions that minimized target-related secondary effects. For both HNF4α and C/EBPα, intravenous injection of specific synthetic siRNAs (siHNF4α and siC/EBPα) resulted in more than 75% reduction in their liver transcript and protein levels 2 days post-injection. For siHNF4α, this coincided with marked and significantly reduced transcript levels of the coagulation genes Hrg, Proz, Serpina5, F11, F12, F13b, Serpinf2, F5, and F9 (in order of magnitude of effect) as compared to levels in control siRNA injected animals. Significant decreases in HNF4α target gene mRNA levels were also observed at 5 days post-siRNA injection, despite a limited level of HNF4α knockdown at this time point. Compared to HNF4α, C/EBPα knockdown had a modest impact on genes encoding coagulation factors. A strong reduction in C/EBPα transcript and protein levels resulted in significantly affected transcript levels of the control genes Pck1 and Fasn and a modest downregulation for coagulation genes Fba, Fbg and F5. F5 and F11 were the sole coagulation genes that were significantly affected upon prolonged (5 day) C/EBPα knockdown. We conclude that in the mouse, HNF4α has a direct and essential regulatory role for multiple hepatic coagulation genes, while a role for C/EBPα is more restricted. In addition, this study demonstrates that synthetic siRNA provides a simple and fast means for determining liver transcription factor involvement in vivo

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Further switched systems

Mixed logical dynamical systems and linear complementarity systems are representations of switched systems, which under the conditions described here are equivalent to the model used in Chapter 4. They are particularly useful for model-predictive control. The equivalences of several hybrid system models show that different models, which are suitable for specific analysis and design problems and have been investigated in detail, cover the same class of hybrid systems. The analysis of the well-posedness of the models leads to conditions on the model equations under which a unique solution exists

Fixation methods for electron microscopy of human and other liver

For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects

Efficacy of MRI in primary care for patients with knee complaints due to trauma:Protocol of a randomised controlled non-inferiority trial (TACKLE trial)

BACKGROUND: Patients with traumatic knee complaints regularly consult their general practitioner (GP). MRI might be a valuable diagnostic tool to assist GPs in making appropriate treatment decisions and reducing costs. Therefore, this study will assess the cost-effectiveness of referral to MRI by GPs compared with usual care, in patients with persistent traumatic knee complaints. DESIGN AND METHODS: This is a multi-centre, open-labelled randomised controlled non-inferiority trial in combination with a concurrent observational cohort study. Eligible patients (aged 18–45 years) have knee complaints due to trauma (or sudden onset) occurring in the preceding 6 months and consulting their GP. Participants are randomised to: 1) an MRI group, i.e. GP referral to MRI, or 2) a usual care group, i.e. no MRI. Primary outcomes are knee-related daily function, medical costs (healthcare use and productivity loss), and quality of life. Secondary outcomes are disability due to knee complaints, severity of knee pain, and patients’ perceived recovery and satisfaction. Outcomes are measured at baseline and at 1.5, 3, 6, 9 and 12 months follow-up. Also collected are data on patient demographics, GPs’ initial working diagnosis, GPs’ preferred management at baseline, and MRI findings. DISCUSSION: In the Netherlands, the additional diagnostic value and cost-effectiveness of direct access to knee MRI for patients presenting with traumatic knee complaints in general practice is unknown. Although GPs increasingly refer patients to MRI, the Dutch clinical guideline ‘Traumatic knee complaints’ for GPs does not recommend referral to MRI, mainly because the cost-effectiveness is still unknown. TRIAL REGISTRATION: Dutch Trial Registration: NTR3689

Efficacy of MRI in primary care for patients with knee complaints due to trauma: Protocol of a randomised controlled non-inferiority trial (TACKLE trial)

Background: Patients with traumatic knee complaints regularly consult their general practitioner (GP). MRI might be a valuable diagnostic tool to assist GPs in making appropriate treatment decisions and reducing costs. Therefore, this study will assess the cost-effectiveness of referral to MRI by GPs compared with usual care, in patients with persistent traumatic knee complaints. Design and methods. This is a multi-centre, open-labelled randomised controlled non-inferiority trial in combination with a concurrent observational cohort study. Eligible patients (aged 18-45 years) have knee complaints due to trauma (or sudden onset) occurring in the preceding 6 months and consulting their GP. Participants are randomised to: 1) an MRI group, i.e. GP referral to MRI, or 2) a usual care group, i.e. no MRI. Primary outcomes are knee-related daily function, medical costs (healthcare use and productivity loss), and quality of life. Secondary outcomes are disability due to knee complaints, severity of knee pain, and patients' perceived recovery and satisfaction. Outcomes are measured at baseline and at 1.5, 3, 6, 9 and 12 months follow-up. Also collected are data on patient demographics, GPs' initial working diagnosis, GPs' preferred management at baseline, and MRI findings. Discussion. In the Netherlands, the additional diagnostic value and cost-effectiveness of direct access to knee MRI for patients presenting with traumatic knee complaints in general practice is unknown. Although GPs increasingly refer patients to MRI, the Dutch clinical guideline 'Traumatic knee complaints' for GPs does not recommend referral to MRI, mainly because the cost-effectiveness is still unknown. Trial registration. Dutch Trial Registration: NTR3689

One-Stage Synovectomies Result in Improved Short-Term Outcomes Compared to Two-Stage Synovectomies of Diffuse-Type Tenosynovial Giant Cell Tumor (D-TGCT) of the Knee: A Multicenter, Retrospective, Cohort Study.

Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120°, p = 0.109; extension 0°, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital