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The interaction of automated vehicles with vulnerable road users is one of the greatest challenges in the development of automated driving functions (ADF). In order to improve efficiency and ensure the safety of mixed traffic, ADF need to understand the intention of vulnerable road users, to adapt to their driving behavior, and to show its intention. However, this communication may occur in an implicit way, meaning they may communicate with vulnerable road users by using dynamic information, such as speed, distance, etc. Therefore, investigating patterns of implicit communication of human drivers with vulnerable road users is relevant for developing ADF. The aim of this study is to identify the patterns of implicit communication of human drivers with vulnerable road users. For this purpose, the interaction between right-turning motorists and crossing cyclists was investigated at a traffic light controlled urban intersection. In the scenario, motorists and cyclists had a green signal at the same time, but cyclist had right-of-way. Using the Application Platform for Intelligent Mobility (AIM) Research Intersection, trajectory and video data were recorded at an intersection in Braunschweig, Germany. Data had been recorded for 4 weeks. Based on the criticality metric post-encroachment time (PET) and quality of the recorded trajectory, 206 cases of interaction were selected for further analyses. According to the video annotation, when approaching the intersection, three common communication patterns were identified: (1) no yield, motorists, who should yield to cyclists, crossed the intersection first while forcing right-of-way; (2) active yield, motorists, who were in front of cyclists, gave the right-of-way; (3) passive yield, motorists, who were behind cyclists, had to give the right-of-way. The analysis of the trajectory data revealed different patterns of changes in time advantage in these three categories. Additionally, the communication patterns were evaluated with regard to frequency of occurrence, efficiency, and safety. The findings of this study may provide knowledge for the implementation of a communication strategy for ADF, contributing to traffic efficiency as well as ensuring safety in the interaction with vulnerable road users., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Dotzauer and Schießl.)

Study Objectives: The psychomotor vigilance task (PVT) is a widely used objective method to measure sustained attention, but the standard 10-min version is often impractical in operational settings. We investigated the reliability and validity of a 3-min PVT administered on a portable handheld device assessing sensitivity to sleep loss and alcohol in relation to a 10-min PVT and to applied tasks., Methods: A total of 47 healthy volunteers underwent a 12 consecutive days sleep lab protocol. A cross-over design was adopted including total sleep deprivation (38 h awake), sleep restriction (SR, 4 h sleep opportunity), acute alcohol consumption, and SR after alcohol intake (SR/Alc 4 h sleep opportunity). Participants performed a 10-min and 3-min PVT and operationally relevant tasks related to demands in aviation and transportation., Results: Sleep loss resulted in significant performance impairments compared with baseline measurements detected by both PVT versions-particularly for mean speed (both p < 0.001)-and the operationally relevant tasks. Similar effects were observed due to alcohol intake (speed: both p < 0.001). The 3-min and 10-min PVT results were highly correlated (speed: between r = 0.72 and r = 0.89). Three of four aviation-related tasks showed robust correlations with the 3-min PVT. Correlations with the parameters of the task related to transportation were lower, but mainly significant., Conclusion: The 3-min PVT showed a high reliability and validity in assessing sleep loss and alcohol-induced impairments in cognitive performance. Thus, our results underline its usefulness as potential fitness for duty self-monitoring tool in applied settings., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The purpose of this study was to find applicable clusters for the development of different treatment pathways in an inpatient multimodal pain-therapy setting based on the multifaceted nature of CLBP. Methods: Based on data of questionnaires (Hospital Anxiety and Depression Scale (HADS), Marburg Questionnaire on Habitual Health Findings (MFHW), quality of life assessment using the Short-Form 12 (SF 12)), a retrospective two-step cluster analysis involving a sample of chronic low back pain (CLBP) patients (N=320) was calculated. Subsequently, the clusters were precisely described and compared on the basis of further data collected during the patients' standard care: pain characteristics, socio-demographic data and the general state of health, psychological variables, therapy intensity, and Diagnosis Related Groups (DRG) data. Results: We found a three-cluster solution: little psychological interference but marginal physical and mental quality of life (Cluster 1); poor well-being, low physical quality of life, and marginal mental quality of life (Cluster 2); and heavy mental strain and marginal physical quality of life (Cluster 3). Conclusions: Similar to previous studies, our results suggest that patients suffering from CLBP differ with regard to the magnitude of mental burden and the presence of physical impairment. These differences ascertain the need for precise targeting of treatment for CLBP. Inpatient pain centers therefore should offer different multimodal therapy pathways and integrate a meaningful triage, taking into account the multifaceted nature of CLBP based on sophisticated knowledge about forms, differences, and relationships among the biopsychosocial components of CLBP., Competing Interests: The authors declare that they have no competing interests. Conflicts might arise if the results of this study lead to a change in the revenue situation in any particular direction., (Copyright © 2019 Langenmaier et al.)

Background: Even though modern concepts of disease management of unspecific low back pain (LBP) postulate active participation of patients, this strategy is difficult to adapt unless multidisciplinary pain therapy is applied. Recently, mobile health solutions have proven to be effective aides to foster self-management of many diseases., Objective: The objective of this paper was to report on the retrospective short-term results of a digital multidisciplinary pain app for the treatment of LBP., Methods: Kaia is a mobile app that digitalizes multidisciplinary pain treatment and is in the market as a medical product class I. For the current study, the data of anonymized Kaia users was retrospectively analyzed. User data were evaluated for 12 weeks regarding duration of use and effect on in-app user reported pain levels, using the numerical rating scale (NRS), depending on whether LBP was classified as acute, subacute, or chronic back pain according to current guidelines., Results: Data of 180 users were available. The mean age of the users was 33.9 years (SD 10.9). Pain levels decreased from baseline NRS 4.8 to 3.75 for all users at the end of the observation period. Users who completed 4, 8, or 12 weeks showed an even more pronounced decrease in pain level NRS (baseline 4.9 [SD 1.7] versus 3.6 [SD 1.5] at 4 weeks; baseline 4.7 [SD 1.8] versus 3.2 [SD [2.0] at 8 weeks; baseline 4.6 [SD 2.2] versus 2.6 [SD 2.0] at 12 weeks). In addition, subgroup analysis of acute, subacute, or chronic classification revealed no significant main effect of group (P>.30) on the reduction of pain. Conclusions: This retrospective study showed that in a pre-selected population of app users, an app digitalizing multidisciplinary rehabilitation for the self-management of LBP reduced user-reported pain levels significantly. The observed effect size was clinically relevant. Ongoing prospective randomized controlled trials (RCTs) will adjust for potential bias and selection effects., Conclusions: This retrospective study showed that in a pre-selected population of app users, an app digitalizing multidisciplinary rehabilitation for the self-management of LBP reduced user-reported pain levels significantly. The observed effect size was clinically relevant. Ongoing prospective RCTs will adjust for potential bias and selection effects., (©Stephan Huber, Janosch A Priebe, Kaja-Maria Baumann, Anne Plidschun, Christine Schiessl, Thomas R Tölle. Originally published in JMIR Rehabilitation and Assistive Technology (http://rehab.jmir.org), 04.12.2017.)

Background: Little is known about ICU physicians' self-confidence and knowledge related to palliative care. Our objective was to investigate self-confidence and knowledge of German ICU physicians related to palliative care, and to assess the impact of work experience, gender, specialty and additional certifications in pain or palliative medicine., Methods: In a multicentre prospective observational study ICU physicians of ten hospitals were asked to rate their self-confidence and to complete a multiple choice questionnaire for the assessment of knowledge. Beyond descriptive statistics and non-parametric tests for group comparisons, linear regression analysis was used to assess the impact of independent variable on self-confidence and knowledge. Spearman's rank test was calculated., Results: 55% of answers in the knowledge test were correct and more than half of the participants rated themselves as "rather confident" or "confident". Linear regression analysis revealed that an additional certificate in either pain or palliative medicine significantly increased both knowledge and self-confidence, but only 15 out of 137 participants had at least one of those certificates. Relation between self-confidence and the results of the knowledge test was weak (r = 0.270 in female) and very weak (r = -0.007 in male)., Conclusions: Although the questionnaire needs improvement according to the item analysis, it appears that, with respect to palliative care, ICU Physicians' self-confidence is not related to their knowledge. An additional certificate in either pain or palliative medicine was positively correlated to both self-confidence and knowledge. However, only a minority of the participants were qualified through such a certificate.

With Intelligent Transport Systems (e.g., traffic light assistance systems) assisted drivers are able to show driving behavior in anticipation of upcoming traffic situations. In the years to come, the penetration rate of such systems will be low. Therefore, the majority of vehicles will not be equipped with these systems. Unequipped vehicles' drivers may not expect the driving behavior of assisted drivers. However, drivers' predictions and expectations can play a significant role in their reaction times. Thus, safety issues could arise when unequipped vehicles' drivers encounter driving behavior of assisted drivers. This is why we tested how unequipped vehicles' drivers (N=60) interpreted and reacted to the driving behavior of an assisted driver. We used a multi-driver simulator with three drivers. The three drivers were driving in a line. The lead driver in the line was a confederate who was followed by two unequipped vehicles' drivers. We varied the equipment of the confederate with an Intelligent Transport System: The confederate was equipped either with or without a traffic light assistance system. The traffic light assistance system provided a start-up maneuver before a light turned green. Therefore, the assisted confederate seemed to show unusual deceleration behavior by coming to a halt at an unusual distance from the stop line at the red traffic light. The unusual distance was varied as we tested a moderate (4m distance from the stop line) and an extreme (10m distance from the stop line) parameterization of the system. Our results showed that the extreme parametrization resulted in shorter minimal time-to-collision of the unequipped vehicles' drivers. One rear-end crash was observed. These results provided initial evidence that safety issues can arise when unequipped vehicles' drivers encounter assisted driving behavior. We recommend that future research identifies counteractions to prevent these safety issues. Moreover, we recommend that system developers discuss the best parameterizations of their systems to ensure benefits but also the safety in encounters with unequipped vehicles' drivers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In 2009 palliative medicine was integrated into the undergraduate curriculum as cross-disciplinary subject 13 and is now part of mandatory education in German medical faculties (MF). Surveys across German MFs have shown an inhomogeneous development of this cross-disciplinary subject. The aim of this study was to assess the current state and the needs in terms of assessments in the cross-disciplinary subject 13 at German MFs., Material and Methods: Palliative care coordinators at German MFs were surveyed by using a standardized telephone interview. Closed-ended questions were analyzed by descriptive analysis and open-ended questions by content analysis., Results: A total of 34 out of 36 MFs participated. Multiple choice tests were the major form of assessment (94.1%) and 9 MFs planned to implement another form of assessment, mainly an objective structured clinical examination (OSCE) station (55.5%). The majority of the MFs (91.2%) had no blueprint to develop assessments but conducted a review (78.8%) afterwards. A successful implementation of the assessment was mostly achieved when the concept of the assessment was felt to be suitable. The lack of human resources was found to be the most relevant obstacle for the implementation of a practical assessment format., Conclusion: The major form of assessment in palliative care is still a written examination, especially multiple choice tests. This format is considered to be of limited value for assessing communicative competencies and attitudes in palliative medical care. Further steps should include the development of a competence-based assessment that is also feasible for smaller MFs with limited resources.

Background: Children suffering from life limiting diseases are frequently cared for by adult palliative care teams due to missing paediatric structures in that field. However it is questionable whether palliative care curricula for physicians comprehensively cover issues of paediatric palliative care (PaedPC)., Aim: To identify all PaedPC issues included in inter-professional or medical palliative care curricula (PCC) and to evaluate the breadth and quality of PaedPC issues covered in these curricula., Design: Inter-professional or medical palliative care curricula (PCC) were identified by an extensive literature review in German and English using the search-engines Google as well as Medline, MedPilot and Pubmed., Results: Worldwide 30 PCC were identified, with only 15 curricula mentioning any PaedPC issues. Of those 15 curricula, up to 22 PaedPC topics were highlighted in each. In 10 or more PaedPC following topics were highlighted: grief and bereavement in family, parents and siblings; communication with children; paediatric malignancies; pain management in PPC and pharmacology. In the majority of PCC curricula where PaedPC issues were identified the following topics were mentioned- grief and bereavement in the family, parents and siblings, communication with children, paediatric malignancies, paediatric pain management and pharmacology., Conclusions: The variability of inclusion of PaedPC issues and the lack of depth and standardisation of knowledge, skills and attitudes in PaedPC issues included in PCC curricula is not sufficient to guide adult palliative care physicians in their clinical work with children suffering from life limiting diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Issue: In 2012 the German medical licensure regulations (Approbationsordnung) made teaching and assessing the conduction of medical consultations a mandatory part of medical education. A catalogue of learning objectives (LO) based on existing references was developed to assist medical schools in meeting this requirement., Methods: A body of relevant material was compiled using literature research and surveying experts. Then, in a multiphase Delphi process, this was evaluated and condensed by an interdisciplinary working group in dialogue with external (clinical) experts. Competence levels and examples of clinical application were assigned to enhance implementation. The catalogue was revised by the medical faculties, professional associations and the BVMD., Results: This learning catalogue comprised 116 learning objectives for the specific skills necessary to conducting medical consultations as well as exemplary application contexts. The catalogue proved to be practical in terms of developing curricula and networking at medical schools., Discussion: This catalogue of learning objectives can serve as the basis for developing a sample communication curriculum for use by medical faculties.

Background: In 2009, palliative medicine became an integrated and compulsory part of undergraduate training in Germany by legislation. After a transitional period, all medical faculties were required to provide adequate teaching with an according examination and certification procedure. In parallel, we conducted bi-annual surveys on all medical faculties in Germany to examine for potential discrepancies between the implementation process and their intended consequences on teaching time and content., Methods: Four consecutive bi-annual surveys (2006, 2008, 2010, 2012) of all 36 medical faculties in Germany were performed, using purposively for this study developed questionnaires. Likert scales and closed questions were analyzed descriptively., Results: Medical Faculty response rate increased from 50 % in 2006 to 88.9 % in 2012. Teaching coordinators in palliative medicine primarily had an anesthesiology or internal medicine background. There was a noted increase over time of the involvement of specialized palliative care units (PCUs) as providing the setting for education. The number of faculties that were able to offer a complete 16 weeks of training in palliative medicine during the "final year" rose steadily. In addition, increased patient-centered teaching formats have been implemented over time. The faculties which offered innovative teaching formats with actors as patients (standardized patient interaction) increased, as did the total number of mandatory examinations. The number of faculties that provided compulsory teaching in a condensed manner within a single academic year increased sharply from 3 of 31 responding faculties in 2010 to 19 of 32 responding faculties in 2012., Conclusions: Until now, teaching conditions and structures in palliative medicine in Germany have proven to be extraordinarily heterogeneous. Although professorships ("Chairs") in palliative medicine proved to be particularly beneficial and supportive in curricular and structural development, only a minority of faculties provide leading academic positions in palliative medicine.

Background: In 2013 palliative medicine (PM) will be integrated into the undergraduate curriculum as part of the mandatory education in German medical universities. The aim of this study is to determine the current state of implementation at German medical faculties (MF)., Methods: All German MFs were contacted using a written postal survey in June 2012., Results: A total of 32 out of 36 MFs participated. Teaching staff consists of 15 or more lecturers in 8 MFs (30 %) and includes psychologists in 24 MFs (75 %) and also nurses in 18 MFs (56 %). Participating physicians are specialized in anesthesiology, internal medicine and general medicine. Teaching staff include palliative outpatient (20 MFs, 63 %) and consultation services (22 MFs, 69 %). Bedside teaching is provided in 15 MFs (47 %). Multiple choice tests are the major form of assessment (29 MFs, 84 %). The total number of teaching units in PM is between 12 and 43 and is usually provided at the end of medical school education. Nurses are employed in the education significantly more in MFs with a chair in PM. General practitioners were engaged only by faculties without a chair in PM., Conclusions: The implementation of the mandatory training in PM at MFs in Germany is inhomogeneous. Further steps include in particular the development of a competence-based curriculum and assessment.

Objectives: To investigate the factors that determine the retentiveness of copings made of cobalt-chromium (CoCr)-alloy or zirconia luted with permanent (solid-body like) and provisional (viscous, elastic-body-like) luting agents., Materials and Methods: We manufactured titanium implant analogs with four-, six-, and eight-taper degrees and copings of CoCr-alloy and zirconia and luted the copings according to a standardized protocol. Samples were thermally cycled, and we investigated the various degrees of roughness of the copings' inner surfaces as well as the various cement mixing ratios on the retentiveness. Copings were either pulled out slowly (by means of a universal testing machine) or knocked out quickly (using a CORONAflex crown replacement device)., Results: The highest level of retentiveness was achieved with a four-taper degree for polycarboxylates followed by zinc-oxide-phosphates and glass ionomers or composite cements. Provisional cements and composite cements containing a plastifier showed significantly lower retentiveness levels. The pull-out and knock-out tests showed a relationship between retentiveness level and taper degree. However, the influence of taper degree was reduced with higher taper degrees as well as with cements that do not set as a solid body due to ingredients such as oily liquids or plastifiers. Thermal cycling further reduced the retentiveness level of these cements. Higher degrees of roughness only improved the retention force of cements setting as a solid body. Mixing errors may alter retentiveness levels in an unpredictable manner. When used within the same group of cements, metal-alloy, and zirconia copings did not differ with regard to their level of retentiveness., Conclusion: Copings made of metal-alloy and zirconia showed no different level of retentiveness when set onto titanium abutments fixed with permanent or provisional cements., Clinical Relevance: Only cements setting as a solid body showed a clear relationship between retentiveness level and taper degree. In contrast, the retentiveness of provisional (viscous, elastic-body-like) luting agents was less predictable.

Decades after the publication of the World Health Organization's analgesic ladder, cancer pain is still a major cause of suffering for patients with cancer and affects millions of people worldwide. Owing to the increasing incidence of cancer, cancer-related pain is a major public health problem worldwide. Unfortunately, current research revealed that available options for the successful treatment of cancer pain is still massively underutilized by physicians, and many patients suffer from insufficiently controlled pain despite available treatment options. This review aims to present a concise update about new data or treatment recommendations from the field of cancer pain management. Therefore, information from guidelines, systematic reviews, and original articles that were published in the year 2012 are presented. Specifically, the publication covers information on tapentadol, fixed oxycodone/naloxone combinations, rapid onset fentanyl, nabiximols, ketamine, denusomab, and specialized psychosocial interventions including early palliative care.

Background: By law in 2013, palliative medicine will be integrated into the undergraduate curriculum as part of a mandatory training program and examinations at German medical schools. For this reason a national curriculum in palliative medicine has to be developed., Aim: The aim of this study was to analyze international undergraduate curricula in palliative medicine, and thus support further curriculum development in Germany., Design: Available international curricula were sought through general search engines (Google, Medline/Pubmed) in German and/or the English language. We used the palliative care education assessment tool (PEAT) for analysis of available curricula. The PEAT comprises 7 domains, and 83 objectives., Results: We identified 17 international undergraduate curricula on palliative medicine. There was a wide variation in curricular design. Mapping the curricula, the results showed that five of the seven PEAT domains were represented in the curricula retrieved. Sixteen objectives were included in more than 75% and 46 objectives in up to 50% of the curricula, respectively. Eighteen objectives were included in less than 25% of the curricula. Three PEAT objectives were absent in all curricula examined., Conclusion: There is an overlap between objectives presented in the PEAT and in the curricula, suggesting that there are "core objectives" such as "respect for differing values," "bereavement process," and "use of opioids" which might be mandatory for undergraduate palliative medical education.

Background: In the context of undergraduate medical education, there is the question of overlap between palliative medicine and pain management. International curricula for palliative medicine were analyzed with regard to the content concerning pain management., Methods: Available international curricula were sought through general search engines (Google, Medline/Pubmed) in the German and English languages. The palliative care education assessment tool (PEAT), a validated instrument for curricula mapping, was used for detection of pain management content. The PEAT comprises 7 domains and 83 objectives. Domain II (pain) contains 12 items (15%). Additional pain management content was analyzed qualitatively., Results: Between 1993 and 2011 16 international curricula for undergraduate education in palliative medicine were identified and every curriculum contained PEAT-domain II (pain). Altogether, 2-65 out of 83 PEAT objectives and 0-11 specific pain-related PEAT objectives were included as learning content. Hence, the latter define 0-21% of the contents of the analyzed curricula. The only additional topic was "breakthrough pain" which was mentioned in 4 out of 16 curricula., Conclusions: Pain-related objectives are regularly mentioned in international undergraduate palliative medicine curricula. The extent is limited and therefore the concordance to general pain management is low.

Objective: Simulations of doctor-patient interactions have become a popular method for the training of medical skills, primarily communication skills. A new questionnaire for the measurement of students' satisfaction with medical courses using this technique is presented, the Student Evaluation Scale for Medical Courses with Simulations of the Doctor-Patient Interaction (SES-Sim)., Method: A set of items focusing on the course quality and the core elements of simulations was created and presented to 220 medical students who had been trained with this method., Results: Based on factor-analyses 18 items were selected for the final version of the scale, which represent five dimensions: learning success, actors, premises, tutors and students. The five dimensions are all significantly correlated with a 1-item-measure of the general satisfaction with the course., Conclusion: The SES-Sim enables tutors to assess in an economic way whether the course has met the students' needs and what can be done better.

Introduction: Patient-controlled analgesia (PCA) has an established role in managing postoperative pain and has been successfully used in-patients with cancer pain. The variation of opioid requirement over a 24h period for patients with cancer pain is debated with suggestions of reduced need over night., Methods: Retrospective review of 10years (1997-2006) data of all in-patients with cancer pain treated with strong opioids delivered by PCA., Results: 141 patients with cancer pain had a mean cumulative 10day morphine equivalent dose per patient of 671mg (median 470mg; range 10-2170mg). At night (10:01pm to 06:00am) the patient's self administered less bolus doses (69mg, (25%)) than during the other two 8h periods (06:01am to 02:00pm, 91mg (33%) and 02:01pm to 10:00pm, 116mg (42%)). In 8 out of 10days a significant variation in bolus requests was observed with significantly less bolus requests during the night (Friedman test, p<0.05). Furthermore, the median number of delivered bolus requests per patient, at night, was 2-3 compared to the morning and afternoon periods of 3-7 and 3.5-6, respectively., Conclusion: PCA met individual patient's opioid needs in a safe and effective manner despite a large inter-individual variability in opioid consumption. Moreover, the study indicated a pattern of less opioid requirement at night., (Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Background: In order to match the interindividual and intraindividual differences in opioid requirements of pediatric oncology patients with mucositis, patient-controlled analgesia (PCA) seems to be the optimal pain therapy option, but scientific data are lacking., Method: A retrospective chart review of PCA-treated children with mucositis was carried out over a 6-year period (2000-2006) at the university hospital for children in Erlangen., Results: The median age of the patients was 12.6 years and they mainly suffered from forms of acute leukemia. Daily morphine equivalent dose (MED) requirements increased with the start of the PCA therapy from 14.5 mg/day to 18.7 mg/day (p=0.021; Wilcoxon test). Children required more opioids by bolus request during the night (10:01 p.m. to 06:00 a.m.; 6.28 mg; 13%) than during the other 8-hour intervals (06:01 a.m. to 02:00 p.m. and 02:01 p.m. to 10:00 p.m.; both 21.3 mg (43.5%) during the whole 10-day study period. In 8 out of 10 days there was a significant diurnal variation in opioid requirement with significantly lower requirement during the night (p<0.05 Friedman test). The median count of delivered and un-delivered bolus requests during the night was 0-1 and 0, respectively., Conclusion: PCA seems to be an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose in children with chemotherapy-induced mucositis. This is expressed through the increase in daily self-administered opioid doses after starting PCA, the huge interindividual variability in opioid consumption and the rare event of an un-delivered bolus request during lock-out time. With the use of a background infusion, additional bolus requests are rare during the night.

Introduction: Studies on opioid use in terminally ill cancer patients have shown a prefinal dose increase in the majority of patients. Mostly oral opioids were used. Due to the pharmacokinetic properties of opioids, it is rather difficult to get a reliable estimate of the true opioid need from those results., Materials and Methods: Retrospectively, we analyzed opioid use during the last week of life of 30 consecutive outpatients with cancer on intravenous (i.v.) morphine patient-controlled analgesia (PCA). A dose increase (decrease) was defined as an increase (decrease) of the patient's individual daily dose by at least 30% with respect to their prior daily dose. We also analyzed circadian variations in morphine use., Results: Thirty patients fulfilled the primary study inclusion criteria. Fulfilling the exclusion criteria, seven patients had to be excluded from analysis (n = 3, on PCA for less than 7 days; n = 4, PCA was finished before death). Twenty-three patients with a total of 161 treatment days were analyzed. The patients' median age was 57 years (range, 4 to 72). The median duration of intravenous morphine PCA was 19 days (range, 8 to 58). The median daily intravenous morphine dose during the last week of life was 96 to 115 mg, without significant change over time/from day to day (Friedman test). On 144/161 days (89.2%), morphine dose remained stable. On 9 treatment days (5.6%), the dose increased, and on 8 days (5.0%), it decreased. In three patients, only dose increases, and in four patients, only dose decreases were observed. In four patients, both dose increases and decreases were observed. Twelve patients showed no change in daily morphine dose. Opioid use lacked a diurnal pattern., Conclusion: During their end-of-life phase, cancer patients on i.v. morphine PCA showed a stable daily opioid need.

Background: In the last week of life, the daily opioid dose in children is highly variable, making the use of patient-controlled analgesia (PCA) a useful therapy option. Scientific data on the use of PCA in paediatric palliative care are rare., Materials and Methods: Retrospective chart review over a 7-year period (Jan 1998-Jan 2005) of PCA treated children dying of cancer was used., Results: Eight children were on PCA for a median duration of 9 days (range, 1 to 50). The daily median intravenous morphine equivalent dose referenced to body weight increased significantly when PCA was initiated and during the last week of life. In the last week of life, the median daily number of delivered and undelivered bolus requests ranged from 7.5-21 and 0-4.5, respectively. To meet children's individual needs, 39 PCA parametre changes on 22 opportunities were performed. Median daily mean pain scores remained low (range, 0-3; numerical rating scale 0-10) throughout the period., Conclusion: PCA proved an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose to effect.

Forty-one patients with 47 basal cell carcinomas (BCCs; 15 superficial, 26 nodular, and 6 sclerodermiform) were treated with 5% imiquimod cream once daily 5 times a week for 6 weeks in an open-label clinical trial. The overall response rate was 95.7%. Local side effects occurred in 68% of the patients as mild to moderate reactions with a clear association to the histological BCC subtype. Follow-up examinations for up to 17 months (median 10 months) showed scars in 14.9% of the patients and a recurrence rate of 6.6%. Overall, imiquimod represents a safe and effective treatment option for a selected cohort of BCC patients. Notably, by the second week of treatment 72.7% of BCC biopsies were histologically tumor-free, which correlated with a substantial decrease of the inflammatory infiltrate by up to 58% between weeks 3 to 6. This early imiquimod response might have important implications for the final definition of potentially shorter imiquimod treatment periods.

Introduction: In the home-care setting, cancer pain patients in need of parenteral analgesia have to be switched to patient-controlled analgesia using portable pumps. But there is a paucity on data on the logistic requirements or the success rate of such a cost-intensive therapy performed by specialized home-care services., Methods: In a retrospective study we analyzed data on care intensity, logistics and outcome of 46 consecutive palliative cancer patients with patient-controlled analgesia (PCA) in a home-care setting., Results: On days 1, 2, and 3 of PCA the switch to parenteral analgesia resulted in a significant increase of the median daily opioid dose in comparison to the dose just prior to PCA. Concurrently, pain scores were significantly reduced. The median duration of PCA was 25 days (range 2-189 days). On average, each patient was seen by the home-care team every 7.4 days. The median duration of the home visits was 60 min (range, 10-190 min). Of the visits 20% were unscheduled, most of these visits being due to problems regarding analgesia. Most patients died at home. Insufficient analgesia required prefinal hospitalization in only a single case., Conclusion: If the indications are correct, intravenous PCA for palliative cancer pain patients results in higher opioid consumption and better pain control. Home-care PCA requires a lot of human and financial resources, but pain-related hospitalization can be prevented.

In pediatric oncology, optimal pain control is still a challenge. A structured pain history and the regular scoring of pain intensity using age-adapted measuring tools are hallmarks of optimal pain control. Psychological measures are as important as drug therapy in the prophylaxis or control of pain, especially when performing invasive procedures. Pain control is oriented toward the WHO multistep therapeutic schedule. On no account should the pediatric patient have to climb up the "analgesic ladder" - strong pain requires the primary use of strong opioids. Give opioids preferably by the oral route and by the clock - short-acting opioids should be used to treat breakthrough pain. Alternatives are i.v. infusion, patient-controlled analgesia, and transdermal applications. Constipation is the adverse effect most often seen with (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic treatment should be given consistently. The assistance of pediatric nurses is of the utmost importance in pediatric pain control. Nurses deliver the basis for rational and effective pain control by scoring pain intensity and documenting drug administration as well as adverse effects. The nurses' task is also to prepare the patient for and monitor the patient during painful procedures. It is the responsibility of both nurse and doctor to guarantee emergency intervention during sedation whenever needed. In our guideline we comment on drug selection and dosage, pain measurement tools, and documentation tools for the purpose of pain control. Those tools may be easily integrated into daily routine.

Based on 4 case reports we focus on the peculiarities of long-term pediatric opioid based pain control. Case report #1, emphasizing the importance of adequate opioid dosing with reference to body weight, illustrates that with adequate management oral sustained-release opioid therapy is safe even in infants less than one year old. Case report #2 is the first report on the usage of buccal fentanyl citrate for pediatric break-through pain control. Case report #3 focuses on the adverse effects of opioid pain control in an infant with neurological impairment. Case report #4 reports on the successful tumor pain control using transdermal buprenorphine. We conclude that proven therapeutic strategies for opioid pain control as applied in adults may be adopted for the usage on children in pediatrics. However, it is mandatory to take into account both the pharmacokinetic and pharmacodynamic peculiarities of childhood.

GPI 15715 is the first water-soluble propofol prodrug that has been studied in humans. Present propofol lipid formulations have well known undesirable properties, for example, pain on injection and increased triglyceride concentrations. We investigated whether GPI 15715 is suitable to achieve and maintain moderate sedation for 2 h. Six male and six female volunteers received a target-controlled infusion of GPI 15715, with an initial propofol target concentration of 1.8 microg/mL and the possibility to adjust the propofol target once after 1 h. Propofol concentrations, the bispectral index, and modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) scores were monitored. The median MOAA/S score was 4 during the first hour and was 3 during the second hour of infusion. The propofol target had to be changed to 2.4 microg/mL in seven volunteers and to 3.0 microg/mL in two volunteers. A propofol concentration of 1.9 microg/mL had the highest probability to result in an MOAA/S score of 3, which corresponds with moderate sedation. We observed no serious side effects. We conclude that GPI 15715 produces excellent sedation.

Background: GPI 15715 is a new water-soluble prodrug that is hydrolyzed to release propofol. The objectives of this crossover study in volunteers were to investigate the pharmacokinetics and pharmacodynamics of GPI 15715 in comparison with propofol emulsion., Methods: In two separate sessions, nine healthy male volunteers (19-35 yr, 70-86 kg) received GPI 15715 and propofol emulsion as a target controlled infusion over 60 min. In the first 20 min, the propofol target concentration increased linearly to 5 microg/ml. Subsequently, the targets were reduced to 3 microg/ml and 1.5 microg/ml for 20 min each. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h and pharmacokinetics were analyzed. The pharmacodynamic effect was measured by the median frequency of the power spectrum of the electroencephalogram, and a sigmoid model with effect compartment was fitted to the data., Results: Compared with propofol emulsion, propofol from GPI 15715 showed a different disposition function and especially larger volumes of distribution. The propofol effect site concentration for half maximum effect was 2.0 +/- 0.5 microg/ml for GPI 15715 and 3.0 +/- 0.7 microg/ml for propofol emulsion (P < 0.05). Propofol from GPI 15715 did not show a hysteresis between plasma concentration and effect., Conclusions: Compared with propofol emulsion, propofol from GPI 15715 showed different pharmacokinetics and pharmacodynamics, particularly a higher potency with respect to concentration. These differences may indicate an influence of the formulation.

The reproducibility of patch tests is an important determinant of the clinical value of this diagnostic procedure. The aim of the present study was to delineate comparatively the efficiency and reproducibility of identical test reagents from 2 different commercial sources. Purchased in duplicate from brial and Boots-Hermal, 30 allergens from the European standard and an extension series were simultaneously applied to Finn Chambers and affixed next to each other. Out of 2070 paired patch tests in 71 patients, 97.2% presented with concordant-negative results. 60 patch tests were classified as allergic with 95% concordant-positive results. From these paired positive patches, a subgroup of 13 (22.8%) corresponding allergens presented with minor differences in the visible strength of the allergic reaction. Generated by cobalt chloride, formaldehyde and 2-bromo-2-nitropropane-1,3-diol in 1 patient each, discordant results, i.e. 1 positive and 1 negative test in parallel, were found in only 5%. Taken together, we were able to demonstrate that patch test preparations from 2 different companies exhibited a high level of reproducibility. This standardized quality of test reagents from different suppliers provides useful information on several aspects of everyday practice.

Background: GPI 15715 (AQUAVAN injection) is a new water-soluble prodrug which is hydrolyzed to release propofol. The objectives of this first study in humans were to investigate the safety, tolerability, pharmacokinetics, and clinical pharmacodynamics of GPI 15715., Methods: Three groups of three healthy male volunteers (aged 19-35 y, 67-102 kg) received 290, 580, and 1,160 mg GPI 15715 as a constant rate infusion over 10 min. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h. Pharmacokinetics were analyzed with compartment models. Pharmacodynamics were assessed by clinical signs., Results: GPI 15715 was well tolerated without pain on injection. Two subjects reported a transient unpleasant sensation of burning or tingling at start of infusion. Loss of consciousness was achieved in none with 290 mg and in one subject with 580 mg. After 1,160 mg, all subjects experienced loss of consciousness at propofol concentrations of 2.1 +/- 0.6 microg/ml. A two-compartment model for GPI 15715 (central volume of distribution, 0.07 l/kg; clearance, 7 ml. kg-1 min-1; terminal half-life, 46 min) and a three-compartment model for propofol (half-lives: 2.2, 20, 477 min) best described the data. The maximum decrease of blood pressure was 25%; the heart rate increased by approximately 35%. There were no significant laboratory abnormalities., Conclusions: Compared with propofol lipid emulsion, the potency seemed to be higher with respect to plasma concentration but was apparently less with respect to dose. Pharmacokinetic simulations showed a longer time to peak propofol concentration after a bolus dose and a longer context-sensitive half-time.

It has been observed that patients with rheumatoid arthritis (RA) respond differently to repetitive painful stimulation. The present study investigated whether this is related to the peripheral or central nervous nociceptive system. EEG-derived potentials and the negative mucosal potential (NMP) from the respiratory epithelium were recorded in response to painful intranasal stimulation with gaseous CO(2). Differences between groups (12 RA patients, 12 controls) were found when stimuli were presented at short intervals. While the NMP did not differ between groups, patients had larger cortical responses to the first stimuli of a series of painful stimuli. This may indicate that in RA central nervous changes of nociceptive processing are present.

The study aimed to investigate the relation of both negative mucosal potentials (NMP) obtained from respiratory epithelium, and pain ratings to repetitive stimulation with CO2 (21 subjects). Trains of four stimuli of identical intensity (70% v/v) were applied at a constant interseries interval (approximately 60 s) but different interstimulus intervals (ISI) of 2 s or 6 s. At an ISI of 6 s, ratings decreased while they increased at an interval of 2 s (P < 0.01). This change was accompanied by the buildup of burning pain probably relating to the 'wind-up' of spinal neurons. In contrast, the decrease of NMP amplitudes was stronger the shorter the ISI (P < 0.01). These findings are in line with the view that the NMP reflects activation of epithelial nociceptors (C-fibers and/or A delta-fibers).