Who contextualises clinical epidemiological evidence? A political analysis of the problem of evidence-based medicine in the layered Dutch healthcare system

We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives.     

Identifying the minimal important difference in patient-reported outcome measures in the field of people with severe mental illness: a pre–post-analysis of the Illness Management and Recovery Programme

Quality of Life Research - Complementary interventions for persons with severe mental illness (SMI) focus on both personal recovery and illness self-management. This paper aimed to identify the...     

Facial Nerve Monitoring under Neuromuscular Blockade

The characteristics of facial nerve electromyography at various levels of neuromuscular blockade are unclear. Partial blockade is well known to facilitate anesthetic safety and management. However, the use of neuromuscular blockage in many skull base procedures is avoided to allow intraoperative facial nerve monitoring.We studied the influence of various levels of neuromuscular blockade on facial nerve stimulation in the New Zealand white rabbit. The facial nerve was exposed in the middle ear of six rabbits. Using electromyographic-type facial nerve monitor, we recorded the facial electromyography signals in these rabbits at increasing levels of vecuronium-induced neuromuscular blockade. All animals demonstrated reliable facial electromyography response at all levels of partial neuromuscular blockade (P < .02). Five of the six animals could be monitored throughout complete blockade. These results clearly demonstrate that rabbit facial electromyography monitoring is possible under neuromuscular blockade. The effect of neuromuscular blockers on facial electromyography monitoring deserves further study, as partial blockade would greatly facilitate the management of anesthesia in otologic, neurotologic, and skull base surgery.     

Contrasts in gait mechanics of individuals with proximal femoral focal deficiency: Syme amputation versus Van Nes rotational osteotomy

Lower-limb kinematics and kinetics during preferred and fast speeds of walking were measured in persons with proximal femoral focal deficiency to compare outcomes after Syme amputation (nine subjects) with those after Van Nes rotational osteotomy (10 subjects). Subjects with a Van Nes rotational osteotomy and full tibial rotation (seven subjects) demonstrated prosthetic knee function during stance as they were able to support a flexed-knee posture at both speeds and produced greater knee-extensor moments at preferred speeds as compared with the Syme group (p < 0.05). Nonprosthetic limb compensatory mechanics were significantly exacerbated in subjects with a Syme amputation compared with the Van Nes group: (a) stance-phase vaulting, resulting in greater inappropriate ankle-power generation at both walking speeds, (b) excessive hip-extensor moments at fast speeds, (c) excessive hip-power absorption and generation at both speeds, and (d) excessive knee-joint power generation at both speeds (p < 0.05). The improved gait after Van Nes rotational osteotomy is one factor that should be considered when making clinical decisions for children with proximal femoral focal deficiency.     

An estimate of the calcium content of the sarcoplasmic reticulum in rat ventricular myocytes

Summary The aim of this paper was to estimate the Ca content of the sarcoplasmic reticulum (s.r.) and to compare this with the amount of Ca which enters the cell via the calcium current in systole. The s.r. Ca content was measured electrophysiologically in voltage-clamped rat ventricular myocytes. Rapid application of caffeine produced a transient increase of [Ca²⁺]_i which was accompanied by a transient inward Na-Ca exchange current. The integral of this current gives a measure of the Ca²⁺ pumped out of the cell by Na-Ca exchange. Ni²⁺ (5 mM) inhibited the current and decreased the rate of fall of [Ca²⁺]_i to 32% of the control suggesting that Na-Ca exchange is responsible for 68% of Ca removal from the cytoplasm following the addition of caffeine. Correcting for the Na-Ca independent Ca removal suggests that the s.r. Ca content is equivalent to about 120 mol per litre cell. Furthermore we estimate that, during systole, Ca entry into the cell via the sarcolemmal calcium current is equal to about 6 % of the Ca content of the s.r.     

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3- fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.      

Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.