The management of breakthrough cancer pain--educational needs a European nursing survey.

Poorly managed cancer pain is well known to profoundly impact the patient's daily life and interfere with quality of life. Nurses who cared for patients with cancer from 12 European countries participated in a survey of breakthrough cancer pain practice. The purpose was to investigate how nurses assess breakthrough cancer pain, use of standardised tools, confidence in supporting patients and awareness of medications. Responses from 1241 participants showed country variations. The majority of the sample was female, Germany had the highest proportion of male nurses (21.0%), followed by Greece (15.8%). A significantly larger proportion of nurses with longer experience and more education (78.8%) used a comprehensive definition of breakthrough cancer pain. Significant variations in training were found; 71% of Finnish nurses had received training compared with 6% of Greek nurses. Training and using a standardised assessment tool was associated with a significant increase in the nurses' perceived ability to distinguish between breakthrough and background pain. Nurses in countries with the highest proportion of training were most confident in supporting patients. In conclusion, there still exists problems with effective management of patients' breakthrough cancer pain, continuing inability to define the difference between background and breakthrough cancer pain leads to poor treatment.

Biomedical students' satisfaction with and engagement in laboratory e-learning support are related to their self-regulation.

Laboratory e-learning support tools can assist students' learning while preparing for laboratory classes. To successfully work in such virtual experimental environments (VEEs) outside class, students require self-regulated learning (SRL) skills. A deeper understanding of the continuous reciprocal interactions between SRL, satisfaction, and online engagement is needed to develop more effective online learning experiences. This study therefore aimed to explore the interconnection between students' satisfaction with, effort/importance and engagement in an exemplary VEE, and to relate this to their perceived SRL and learning outcomes. Based on surveys in 79 university students, SRL was related to VEE engagement, effort/importance, and satisfaction. VEE engagement and satisfaction were not related to learning outcomes, while SRL and effort were. Students with different SRL also tended to interact differently with the VEE and experienced differing degrees of procedural and feedback support by the e-environment. We conclude that, for optimal learning experience and outcomes, students' effort regulation and SRL need to be supported while interacting with the VEE, preferably by interventions that integrate personalized and adaptive features. This study has implications for designing and optimizing VEEs and indicates that future research should focus on VEEs taking students' SRL and effort regulation into account to support individual learners effectively.

[The isocentric C-arm. Visualization of fracture reduction and screw position in the radius]. / Isozentrischer C-Bogen. Visualisierung simulierter Frakturreposition und Schraubenpositionierung am Radius.

In addition to conventional C-arms which can be used for intraoperative imaging, C-arm image amplifiers with an option for three-dimensional imaging (ISO-C3D) are available to visualize reduction of fragments and positions of implants. In ten cadaver wrists intra-articular steps and intra-articular screw positions were simulated. Images obtained by conventional two-dimensional C-arm image amplifier, computed tomography and ISO-C3D were evaluated by four investigators using a questionnaire. For 2D image amplifier scans the investigators rated the quantity of the articular steps correctly in 45%, incorrectly in 51% and were uncertain in 4%. Concerning CT scans these values were 57, 40 and 3%, respectively. With a slow 190° ISO-C3D mode the investigators rated the steps correctly in 47%, incorrectly in 44% and were uncertain in 9%. The positions of the tip of the screw were rated correctly for 2D scans in 56%, incorrectly in 40% and were uncertain in 4%. For CT screw positions were assessed correctly in 40%, incorrectly in 43% and were uncertain in 17%. For ISO-C3D in fast 190° mode the rating was correct in 59%, wrong in 30% and uncertain in 11%. In the slow Iso-C3D mode the results were inferior with correct assessment in 51%, wrong results in 36% and uncertain evaluation in 13%. In our cadaveric study, ISO-C3D scans have been found valuable for intraoperative controls of implant positions and assessment of intra-articular steps.

[Early functional treatment and full weight-bearing of surgically treated isolated ankle fractures in the elderly]. / Frühfunktionelle Behandlung und Vollbelastung operativ versorgter isolierter Aussenknöchelfrakturen beim älteren Patienten.

QUESTION: Fractures of the ankle joint belong to the most often occurring injuries. The aftercare in plaster lasts several weeks and is problematic especially in elderly patients. METHODS: In a retrospective study patients over the age of 50 years who underwent surgical treatment of ankle fractures and early functional mobilization were examined in a follow-up. The range of motion, the circumferential measurements and the radiological course were examined by comparing preoperative and postoperative X-ray images after 13-24 months. The subjective results were collected using the Olerud-Molander score (OMS). RESULTS: A total of 30 out of 42 patients who qualified for the follow-up were included in the study. The distribution of the gender was equal as was the right/left distribution and the mean age was 68 years. The magnitude of movement and comparison between the two sides showed no significant differences. The average score for subjective satisfaction was 90 in the OMS. The radiological results showed few changes and no deviations from the axis. No redislocations or implant fractures could be observed. Early functional full weight-bearing showed satisfactory preliminary results. CONCLUSION: This treatment concept can be recommended because patient comfort is increased and the risk of immobilization is excluded.

Improved intra-operative reduction control using a three-dimensional mobile image intensifier - a proximal tibia cadaver study.

This study aimed to analyse whether the precision of a three-dimensional mobile image intensifier (ISO-C 3D) differs from conventional two-dimensional fluoroscopy and high resolution CT scan in a fracture model of the proximal tibia. A depression fracture of the medial plateau (AO/OTA 41-B2.3) was created in 12 formalin-fixed, human cadaver knees. The cartilage of the depression could be positioned above (+1mm, +2mm), below (-1mm, -2mm), or in line with the joint surface. Fluoroscopy, computed tomography (CT) scans, and ISO-C 3D scans (four different protocols: 100 images, 66 images, 50 images, and 33 images) were done for each fracture level. Three independent observers assessed each imaging set. The difference between the estimated reduction and the real reduction was used for statistical analysis. Our hypothesis was that no differences in the precision exist between the imaging techniques (p<0.05). The conventional image intensifier group (0.7 mm+/-0.67) showed significantly higher deviations than the CT group (0.3 mm+/-0.43; p<0.001) and significantly higher deviations than all ISO-C 3D groups (0.4-0.5 mm; p<0.001). Of the ISO-C 3D groups, only the scan protocol with the lowest number of images (0.5 mm+/-0.51) showed significantly lower precision than the CT group (p<0.001). It was concluded that the three-dimensional mobile image intensifier showed higher precision in reduction assessment in a fracture model of the tibial plateau compared to fluoroscopy. High resolution CT scans should remain the standard for post-operative assessment of reduction outside the operating theatre.

Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes.

Aldosterone infusion into the 4th ventricle (4th V), upstream the nucleus of the solitary tract (NTS), produces strong 0.3 M NaCl intake. In the present study, we investigated whether aldosterone infusion into the 4th V activates HSD2 neurons, changes renal excretion, or alters blood pressure and cardiovascular reflexes. Chronic infusion of aldosterone (100 ng/h) into the 4th V increased daily 0.3 M NaCl intake (up to 44 ±â€¯10, vs. vehicle: 5.6 ±â€¯3.4 ml/24 h) and also c-Fos expression in HSD2 neurons in the NTS and in non-HSD2 neurons in the NTS. Natriuresis, diuresis and positive sodium balance were present in rats that ingested 0.3 M NaCl, however, renal excretion was not modified by 4th V aldosterone in rats that had no access to NaCl. 4th V aldosterone also reduced baroreflex sensitivity (-2.8 ±â€¯0.5, vs. vehicle: -5.1 ±â€¯0.9 bpm/mmHg) in animals that had sodium available, without changing blood pressure. The results suggest that sodium intake induced by aldosterone infused into the 4th V is associated with activation of NTS neurons, among them the HSD2 neurons. Aldosterone infused into the 4th V in association with sodium intake also impairs baroreflex sensitivity, without changing arterial pressure.

Local inputs to aldosterone-sensitive neurons of the nucleus tractus solitarius.

Aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) become activated during sodium depletion and could be key neural elements regulating sodium intake. The afferent inputs to these neurons have not yet been defined, but one source may be neurons in the area postrema, a neighboring circumventricular organ that innervates the NTS and exerts a powerful inhibitory influence on sodium appetite [Contreras RJ, Stetson PW (1981) Changes in salt intake after lesions of the area postrema and the nucleus of the solitary tract in rats. Brain Res 211:355-366]. After an anterograde axonal tracer was injected into the area postrema in rats, sections through the NTS were immunolabeled for the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), a marker for aldosterone-sensitive neurons, and examined by confocal microscopy. We found that some of the aldosterone-sensitive neurons received close appositions from processes originating in the area postrema, suggesting that input to the HSD2 neurons could be involved in the inhibition of sodium appetite by this site. Axonal varicosities originating from the area postrema also made close appositions with other neurons in the medial NTS, including the neurotensin-immunoreactive neurons in the dorsomedial NTS. Besides these projections, a dense field of neurotensinergic axon terminals overlapped the distribution of the HSD2 neurons. Neurotensin-immunoreactive axon terminals were identified in close apposition to the dendrites and cell bodies of some HSD2 neurons, as well as unlabeled neurons lying in the same zone within the medial NTS. A local microcircuit involving the area postrema, HSD2 neurons, and neurotensinergic neurons may play a major role in the regulation of sodium appetite.

Navigated percutaneous pelvic sacroiliac screw fixation: experimental comparison of accuracy between fluoroscopy and Iso-C3D navigation.

Percutaneous sacroiliac screw fixation is technically demanding and can result in complications mainly related to imaging problems. Furthermore, the conventional technique performed using fluoroscopic control is associated with a long radiation exposure. The purpose of this study was to evaluate the accuracy of two navigation technologies used in traumatology; fluoroscopy and Iso-C3D navigation. A total of 40 screws were placed (20 with Iso-C3D, 20 with 2D fluoroscopy) at levels S1 and S2. With both technologies, all S1 screws could be placed correctly, but four (10%) incorrect placements were seen at S2 with fluoroscopy navigation. With all Iso-C3D navigated drillings, no perforation was seen. Iso-C3D navigation therefore proved superior to 2D fluoroscopy navigation for sacroiliac screw fixation in an experimental set-up designed to assess accuracy.

Implementation of a new navigated parallel drill guide for femoral neck fractures.

Trauma navigation modules often use conventional mechanical surgical tools for basic simulation of drilling procedures or single screw placement. However, the precise parallel placement or specific angles that may be required are not displayed on the navigation screen. A more complex mechanical tool, a parallel drill guide (PDG) for femoral neck fractures, was integrated into a navigation module as part of this study, thus combining the advantages of mechanical tools with the benefits of fluoroscopic navigation. To implement a conventional PDG with a conventional navigation system, the tool was equipped with a non-detachable reflective marker array. Navigation engineers adapted the software to enable the navigated PDG to be displayed. We evaluated the conventional technique in comparison with the navigated technique using plastic bone models and a fresh frozen cadaver. Implementation of the navigated PDG did not pose any problems, in terms of either the software or the surgical procedure itself. The total operation time was extended by 30%, but the radiation time for the navigated group was reduced by 50%. No software or hardware-related failures occurred. Complete integration of a cannulated parallel drill guide into a navigation system has been successfully implemented. Continuous display of the mechanical guide with two parallel trajectories on the navigation screen enables safe, efficient screw placement within mechanical guidelines, without the need for additional radiographic control once initial registration has been completed.

Preliminary clinical experience using a newly developed minimal-invasive reference base in computer assisted foot surgery.

In recent years, many new tools and techniques have been developed in computer assisted orthopaedic surgery primarily with an industry led effort in software innovation and development. Only a few research and clinical projects have focused on intraoperative difficulties. A common operative challenge in computer assisted orthopaedic surgery is the positioning of the reference base. Rigid fixation of a dynamic reference base is essential in navigated surgery of the extremities. The aim of this study was to develop a minimal-invasive screw which could be placed effectively and efficiently with rotational stability during computer assisted orthopaedic surgery. The minimal-invasive screw was initially evaluated in an artificial bone experiment. After successful results with the artificial bone experiment, it underwent testing in seven human cadaver thighs with ISO-C3D navigated drilling. Finally the screw was transferred into a clinical application during five foot surgeries. In 10 ISO-C3D navigated drillings, the lesions were targeted 100% of the drillings. A screw dislocation was not observed. In comparison to conventional one or two pin fixation systems, the newly designed small screw did not have any observed side effects such as artifacts. In addition, the screw generated less heterodyning than a conventional fixation system. The small screw design is an advantage in theatre. We believe the minimally-invasive screw allows the surgeon to use a tool that helps avoid common pitfalls from conventional fixation systems, and it may improve efficiency.

Accuracy study of computer-assisted drilling: the effect of bone density, drill bit characteristics, and use of a mechanical guide.

OBJECTIVE: This study was designed to determine the clinical relevant accuracy of CT-based navigation for drilling. DESIGN: Experimental model. SETTING: Laboratory. METHODS: Twelve drills of varying lengths and diameters were tested with 2 different set-ups. Group 1 used free-hand navigated drilling technique with foam blocks equipped with titanium target points. Group 2 (control) used a newly developed 3-dimensional measurement device equipped with titanium target points with a fixed entry for the navigated drill to minimize bending forces. One examiner performed 690 navigated drillings using solely the monitor screen for control in both groups. The difference between the planned and the actual starting and target point (up to 150 mm distance) was measured (mm). STATISTICS: Levene test and a nonpaired t test. Significance level was set as P < 0.05. RESULTS: The core accuracy of the navigation system measured with the 3-dimensional device was 0.5 mm. The mean distance from planned to actual entry points in group 1 was 1.3 (range, 0.6-3.4 mm). The mean distance between planned and actual target point was 3.4 (range, 1.7-5.8 mm). Free-hand navigated drilling showed an increased difference with increased length of the drill bits as well as with increased drilling channel for drill bits 2.5 and 3.2 mm and not for 3.5 and 4.5 mm (P < 0.05). CONCLUSIONS: The core accuracy of the navigation system is high. Compared with the navigated free-hand technique, the results suggest that drill bit deflection interferes directly with the precision. The precision is decreased when using small diameter and longer drill bits.

[Intraoperative three-dimensional imaging with an isocentric mobile C-arm at the wrist]. / Intraoperative 3D-Bildgebung am Handgelenk mit einem mobilen isozentrischen C-Bogen.

In addition to conventional radiological C-arm image amplifiers used for intraoperative imaging, now a new mobile C-arm image amplifier with an option for three dimensional imaging (Iso-C 3D) is available to visualize reduction of fractures and position of implants. In a wrist-model three titanium pins were placed and three holes of different length were drilled. Distances between the pins and the depths of the drilled holes were calculated in conventional computer tomographic scans and Iso-C 3D scans in perpendicular, 30 degree and 90 degree position of the gantry and compared to actual distances and depths. There were no significant differences between the actual measured distances and those measured by CT scans and Iso-C 3D scans. Furthermore, gantry position had no significant effect upon the results. Iso-C 3D scans are as reliable as conventional CT scans for intraoperative controlling of implant positioning.

Orexin neurons project to diverse sympathetic outflow systems.

The viral transneuronal labeling method was used to demonstrate that orexin-containing neurons of the lateral hypothalamic area (LHA) are linked via multisynaptic connections to different sympathetic outflow systems. Two different types of transneuronal tracing experiments were performed: single- and double-virus studies. In the first series of experiments, Bartha pseudorabies virus (PRV), a retrograde transneuronal tracer, was injected into single sympathetic targets, viz., stellate ganglion, adrenal gland, celiac ganglion, and kidney. Six to 7 days post-injection, orexin (hypocretin) neurons were transneuronally labeled. In a second set of experiments, the double-virus tracing method was used to determine whether single orexin LHA neurons are linked to two different sympathetic outflow systems. Two isogenic forms of Bartha PRV were used that differed by a single gene. beta-Galactosidase Bartha PRV was injected into the stellate ganglion and green fluorescent protein Bartha PRV into the adrenal gland of the same rat. The reverse placement of viral injections was made in another set of rats. In both paradigms, some orexin LHA neurons were transneuronally labeled with both viruses, indicating that they are capable of modulating multiple sympathetic outflow systems. These findings raise the possibility that orexin LHA neurons regulate general sympathetic functions, such as those that occur during arousal or the fight-or-flight response.

Primary subtalar arthrodesis of calcaneal fractures.

We evaluated retrospectively the long-term results of isolated calcaneal fractures treated with open reduction and internal fixation and a primary subtalar arthrodesis. From 1990 to 1997 258 patients were treated with a calcaneal fracture, for the current study six patients were included. Six different surgeons operated on the patients. The indication for the fusion was based on the comminution of the posterior facet according to the preoperative CT as well as the intraoperative evaluation of destruction of the cartilage. The restoration of length, axes and angles of the calcaneus was almost anatomical in all cases. Follow-up was done at a mean of 4.9 (2.5 - 7.5 years). Using the AOFAS score, the results were good or excellent in five patients. In one patient with a painful arthritis in the talonavicular joint and hyperesthesia of the sural nerve, the results were fair. All returned to their profession within 9 months and had no or only minor daily restrictions. The results are comparable with single surgeon series. We found open reconstruction of the calcaneus with primary fusion of the subtalar joint may be indicated in selected patients and, in these 6 patients led to good results.

[Computer-assisted surgery for pelvic injuries]. / Rechnergestütztes Operieren bei Beckenverletzungen.

For pelvic fractures, pre- and postoperative imaging includes spiral computed tomography, providing high resolution and accuracy. In conventional pelvic operations, these image data cannot be used directly. Intraoperative imaging is limited with fluoroscopy and visualization by the approaches. One solution in terms of precision and reduction of radiation exposure could be computer-assisted surgery (CAS). This method can be divided into navigation, which requires active registration, CT based navigation and registration-free fluoroscopy-based or Iso-C-3D-based navigation. Applications for CAS in the pelvis include sacroiliac screw osteosynthesis in pelvic ring fractures, navigated periacetabular screw fixation, and correction operations for malhealed pelvic ring fractures. Nowadays, CAS is still costly and frequently requires additional staff. However, it helps to reduce complications caused by implant placement. With the introduction of new health care requirements in Germany, this may be an economic argument as well. Current developments focusing on accurate navigated reduction will provide new indications for CAS, further decrease complication rates, and help to reduce the invasiveness of pelvis operations.

Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration.

BACKGROUND AND PURPOSE: The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces hepatic steatosis and has been suggested to reduce atherosclerosis; however, its effects on liver inflammation are underexplored. Here, we tested the hypothesis that exendin-4 reduces inflammation in both the liver and vessel wall, and investigated the common underlying mechanism. EXPERIMENTAL APPROACH: Female APOE*3-Leiden.CETP mice, a model with human-like lipoprotein metabolism, were fed a cholesterol-containing Western-type diet for 5 weeks to induce atherosclerosis and subsequently treated for 4 weeks with exendin-4. KEY RESULTS: Exendin-4 modestly improved dyslipidaemia, but markedly decreased atherosclerotic lesion severity and area (-33%), accompanied by a reduction in monocyte adhesion to the vessel wall (-42%) and macrophage content in the plaque (-44%). Furthermore, exendin-4 reduced hepatic lipid content and inflammation as well as hepatic CD68⁺ (-18%) and F4/80⁺ (-25%) macrophage content. This was accompanied by less monocyte recruitment from the circulation as the Mac-1⁺ macrophage content was decreased (-36%). Finally, exendin-4 reduced hepatic chemokine expression in vivo and suppressed oxidized low-density lipoprotein accumulation in peritoneal macrophages in vitro, effects dependent on the GLP-1 receptor. CONCLUSIONS AND IMPLICATIONS: Exendin-4 reduces inflammation in both the liver and vessel wall by reducing macrophage recruitment and activation. These data suggest that exendin-4 could be a valuable strategy to treat NASH and atherosclerosis simultaneously.

The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

BACKGROUND AND PURPOSE: Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. EXPERIMENTAL APPROACH: Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The extent to which the insulin sensitizing effects of topiramate were mediated through the CNS were determined by concomitant i.c.v. infusion of vehicle or tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The direct effects of topiramate on insulin signalling and glucose uptake were assessed in vivo and in cultured muscle cells. KEY RESULTS: In hyperinsulinaemic-euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (∼4 µg·mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2-deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin-mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate was completely abrogated. Topiramate did not directly affect glucose uptake or insulin signalling neither in vivo nor in cultured muscle cells. CONCLUSION AND IMPLICATIONS: In conclusion, topiramate stimulates insulin-mediated glucose uptake in vivo through the CNS. These observations illustrate the possibility of pharmacological modulation of peripheral insulin resistance through a target in the CNS.