[Outpatient palliative medicine : Attitudes in the care of palliative emergencies. Prospective questionnaire-based investigation]. / Ambulante Palliativmedizin : Einstellungen in der Versorgung palliativer Notfälle. Prospektive Fragebogenuntersuchung.

BACKGROUND: The right to adequate outpatient palliative care has existed for several years in Germany. In recent years outpatient palliative care has developed very positively. Nevertheless, in emergency situations paramedics and emergency physicians were often included in the care of palliative care of patients. The aim of our study was to investigate the cooperation between outpatient palliative care teams and the emergency medical services. Another aim was to identify structural realities and based on these to discuss the possibilities in the optimization of outpatient palliative medical emergency situations. METHODS: A standardized self-designed questionnaire was distributed to specialized outpatient palliative care teams (SPCS) in Germany. For this purpose, closed and open questions (mixed methods) were used. The evaluation was carried out according to the questionnaire categories in quantitative and qualitative forms. The questionnaire was subdivided into general information and specific questions. RESULTS: The survey response rate was 79% from a total of 81 SPCS in 2011. The following standards in palliative emergency care were recommended: (1) early integration of outpatient palliative care services and basic outpatient palliative care systems, (2) end-of-life discussions, (3) defined emergency medical documents, emergency drug boxes, do not attempt resuscitation orders and (4) emergency medical training (physicians and paramedics). CONCLUSION: Outpatient palliative care in Germany has developed very positively during the last years; however, there are still deficits in terms of optimal patient care, one of which refers to the treatment of palliative care emergencies. In this context, optimization in the cooperation between outpatient palliative care services and emergency medical services should be discussed.

CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.

BACKGROUND: New treatment options are required for patients with asthma not sufficiently controlled with inhaled therapies. In a Phase 2a trial, CYT003, a Toll-like receptor-9 agonist immunomodulator, improved asthma control during inhaled glucocorticosteroid reduction in patients with allergic asthma. This double-blind Phase 2b study assessed the efficacy and safety of CYT003 in patients with persistent moderate-to-severe allergic asthma not sufficiently controlled on standard inhaled glucocorticosteroid therapy with/without long-acting beta-agonists (LABAs). METHODS: Overall, 365 patients received seven doses of subcutaneous CYT003 (0.3, 1, or 2 mg) or placebo as add-on therapy to conventional controller medication. Change from baseline in Asthma Control Questionnaire (ACQ) score was the primary outcome; secondary outcomes included change in forced expiratory volume, Mini Asthma Quality of Life Questionnaire, and safety. RESULTS: All groups, including placebo, showed a clinically important improvement in ACQ score; however, there was no significant difference between the CYT003 and placebo groups at week 12 (least-squares mean difference 0.3 mg: -0.027 [95% confidence interval -0.259 to 0.204]; 1 mg: 0.097 [-0.131 to 0.325]; 2 mg: 0.081 [-0.148 to 0.315]). No significant differences were seen in secondary outcomes. CYT003 was well tolerated; the most common treatment-emergent adverse events were injection site reactions. Due to lack of efficacy, the study was prematurely terminated at the end of the treatment phase with no further follow-up. CONCLUSIONS: Toll-like receptor-9 agonism with CYT003 showed no additional benefit in patients with insufficiently controlled moderate-to-severe allergic asthma receiving standard inhaled glucocorticosteroid therapy with or without LABAs.

[Simulation as possible training for palliative emergencies: prospective initial data analysis of participants from two simulation training sessions]. / Simulation als Möglichkeit zum Training palliativer Notfälle : Prospektive erste Datenanalyse von Teilnehmern zweier Simulationstrainings.

BACKGROUND: Palliative emergencies describe an acute situation in patients with a life-limiting illness. At present defined curricula for prehospital emergency physician training for palliative emergencies are limited. Simulation-based training (SBT) for such palliative emergency situations is an exception both nationally and internationally. AIM: This article presents the preparation of recommendations in the training and development of palliative care emergency situations. MATERIAL AND METHODS: A selected literature search was performed using PubMed, EMBASE, Medline and the Cochrane database (1990-2013). Reference lists of included articles were checked by two reviewers. Data of the included articles were extracted, evaluated und summarized. In the second phase the participants of two simulated scenarios of palliative emergencies were asked to complete an anonymous 15-item questionnaire. The results of the literature search and the questionnaire-based investigation were compared and recommendations were formulated based on the results. RESULTS: Altogether 30 eligible national and international articles were included. Overall, training curricula in palliative emergencies are currently being developed nationally and internationally but are not yet widely integrated into emergency medical training and education. In the second part of the investigation, 25 participants (9 male, 16 female, 20 physicians and 5 nurses) were included in 4 multiprofessional emergency medical simulation training sessions. The most important interests of the participants were the problems for training and further education concerning palliative emergencies described in the national and international literature. CONCLUSION: The literature review and the expectations of the participants underlined that the development and characteristics of palliative emergencies will become increasingly more important in outpatient emergency medicine. All participants considered palliative care to be very important concerning the competency for end-of-life decisions in palliative patients. For this reason, special curricula and simulation for dealing with palliative care patients and special treatment decisions in emergency situations seem to be necessary.

Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML.

Reproductive factors and Parkinson's disease risk in Danish women.

BACKGROUND AND PURPOSE: Parkinson's disease is more common in men than women by a ratio of about 1.5:1 and yet there is no consensus to date as to whether female reproductive factors including hormone use affect Parkinson's disease risk. Our objective was to examine the relationship between Parkinson's disease and female reproductive factors in the largest population-based Parkinson's disease case-control study to date. METHODS: Seven hundred and forty-three female Parkinson's disease cases diagnosed between 1996 and 2009 were selected from the Danish National Hospital Register, diagnoses confirmed by medical record review, and the cases were matched by birth year to 765 female controls randomly selected from the Danish Civil Registration System. Covariate information was collected in computer-assisted telephone interviews covering an extensive array of topics including reproductive and lifestyle factors. RESULTS: After adjusting for smoking, caffeine and alcohol use, education, age, and family Parkinson's disease history, inverse associations between Parkinson's disease and early menarche (first period at ≤11 years), oral contraceptives, high parity (≥4 children) and bilateral oophorectomy were found; adjusted odds ratios and 95% confidence limits were respectively 0.68 (0.45-1.03) for early menarche, 0.87 (0.69-1.10) for oral contraceptives, 0.79 (0.59-1.06) for high parity and 0.65 (0.45-0.94) for bilateral oophorectomy. Little support for associations between Parkinson's disease and fertile life length, age at menopause or post-menopausal hormone treatment was found. CONCLUSIONS: Reproductive factors related to women's early- to mid-reproductive lives appear to be predictive of subsequent Parkinson's disease risk whereas factors occurring later in life seem less important.

Treatment with corticosteroids and the risk of anastomotic leakage following lower gastrointestinal surgery: a literature survey.

AIM: Background Anastomotic leakage is a serious complication in colorectal surgery. Treatment with corticosteroids is known to impair wound healing but their effect on the healing of a colorectal anastomosis remains unclear, and studies have reported conflicting results. Objective The aim of this study was to evaluate the current evidence regarding the effect of corticosteroids on the risk of anastomotic leakage following colorectal surgery. METHOD: Search strategy A systematic review was conducted following a search of PubMed and Embase. Selection criteria Inclusion criteria were studies published in English and involving humans. A minimum cohort of 50 patients was required and anastomoses involving the ileum, colon and rectum were included. Studies that investigated corticosteroids as a risk factor for anastomotic leakage were included regardless of the duration and the dose of corticosteroids. Data Collection and analysis A comparison was conducted between anastomotic leakage in noncorticosteroid- and corticosteroid-treated patients. The main outcome measure was the risk of anastomotic leakage. RESULTS: Twelve studies with a total of 9564 patients were included in the review. In total, 1034 patients received corticosteroids in the preoperative period, and 344 patients were diagnosed with anastomotic leakage, 70 of whom had received corticosteroids. Six of the 12 studies showed an increased risk for anastomotic leakage in the corticosteroid group. Overall, the anastomotic leakage rate was 6.77% (95% CI: 5.48-9.06) in the corticosteroid group and 3.26% (95% CI: 2.94-3.58) in the noncorticosteroid group. CONCLUSION: Caution should be shown in patients scheduled for lower gastrointestinal surgery with anastomosis.

[Perioperative care of palliative patients by the anesthetist : medical, psychosocial and ethical challenges]. / Perioperative Betreuung von Palliativpatienten durch den Anästhesisten : Medizinische, psychosoziale und ethische Herausforderungen.

Anesthetists will encounter palliative patients in the daily routine as palliative patients undergo operations and interventions as well, depending on the state of the disease. The first challenge for anesthetists will be to recognize the patient as being palliative. In the course of further treatment it will be necessary to address the specific problems of this patient group. Medical problems are optimized symptom control and the patient's pre-existing medication. In the psychosocial domain, good communication skills are expected of anesthetists, especially during the preoperative interview. Ethical conflicts exist with the decision-making process for surgery and the handling of perioperative do-not-resuscitate orders. This article addresses these areas of conflict and the aim is to enable anesthetists to provide the best possible perioperative care to this vulnerable patient group with the goal to maintain quality of life and keep postoperative recovery as short as possible.

[Anesthesiological acute pain therapy in Germany: telephone-based survey]. / Anästhesiologische Akutschmerztherapie in Deutschland: Telefonbasierte Umfrage.

INTRODUCTION: The last survey of anesthesiological acute pain therapy in Germany was conducted in 1999. Since then new organisational as well as therapeutic aspects have developed. Amongst others the operation and procedures key (OPS) figure 8-919 complex acute pain therapy has been introduced in the German medical billing system, with the restriction that it cannot currently be redeemed. There is an ongoing debate on the role of epidural analgesia in acute pain therapy and new oral medication concepts have been established. Therefore a survey of the present state of acute pain therapy in Germany was conducted. METHODS: Based on a list of all 1,356 hospitals in Germany a randomized list of 412 hospitals was generated. Out of these 412 hospitals those with anesthesiology departments (378 hospitals) were contacted via telephone and asked to participate in the survey. Out of the 378 hospitals 285 (75.4 %) agreed to take part. The survey consisted of a questionnaire containing closed and open questions regarding organisational and therapeutic aspects of acute pain therapy. The ethics committee of the University of Regensburg rated the survey as not being subject to approval due to the lack of personal patient data. RESULTS: Of the participating hospitals 183 (64.2 %) had an acute pain service (APS) and of these 107 (58.5 %) met the quality criteria of the OPS 8-919. This figure however, was only consistently documented by 40 (37 %) APSs. Epidural analgesia (EA) was offered by 275 (96.5 %) hospitals and patient-controlled intravenous analgesia (PCA) by 255 (89.5 %). Likewise, 255 (89.5 %) hospitals used controlled-released opioids in acute pain therapy. Concerning EA, the medications most used were sufentanil as an opioid and ropivacaine as a local anesthetic in255 (92.7 %) of the hospitals with EA for sufentanil and 253 (92 %] for ropivacaine. An EA was offered on regular wards in 240 (87.3 %) hospitals. Uncertainty existed about concrete limits for coagulation values before removal of an epidural catheter. The opioid most utilized in PCA was piritramide with some hospitals using morphine or oxycodone (92.2 %, 9.4 % and 9.4 %, respectively). Other opioids, such as hydromorphone and tramadol were rarely used and remifentanil was not used at all. Oral medication was widely used with metamizole being the non-opioid analgesic and oxycodone/naloxone the controlled-release opioid being prescribed the most. New antiepileptic drugs, such as gabapentin or pregabalin were rarely employed in acute pain therapy. CONCLUSIONS: Since 1999 the number of hospitals that have implemented an APS has risen from 36.1 % to 64.2 %. The lack of consistent documentation of the OPS 8-919 will probably not increase the likelihood that it will become redeemable in the near future. Certain therapy methods, such as EA and PCA were still well established with oral therapy gaining in significance. The uncertainty regarding limits for coagulation values before removal of an epidural catheter could perhaps be reduced by a statement from the German Society of Anesthesia and Intensive Care.

Messengers of renal graft quality during warm and cold ischemia: a porcine microdialysis study.

INTRODUCTION: Little is known about local graft metabolism during warm and cold ischemia before renal transplantation. We sought to characterize local metabolic changes in renal grafts during storage to understand acceptable ischemia time. METHODS: Kidneys from 60- or 15-kg pigs were randomized to cold (4°C) or warm (37°C) storage. Local renal graft metabolism was monitored for 24 hours by use of microdialysis and measurements of glycerol, glutamate glucose and lactate. RESULTS: For all metabolites, there was a significant interaction between time, storage temperature, and kidney size (all P < .0001). For local glycerol and glutamate, a significant increase was observed initially during warm storage, reaching a high steady state level. Glycerol remained low in cold kidneys for 80 minutes, but after 100 minutes there was an ongoing increase (P = .003) with no steady-state maximum level reached during the first 24 hours. The curves in the 2 size groups were parallel (P = .384) with 74% higher glycerol content in large kidneys (P = .005). Glutamate increased in cold kidneys in a similar manner in the 2 size groups (P = .924). Warm storage caused a rapid glucose decline within 60-100 minutes. In cold storage, glucose remained at a steady level until 480 minutes. CONCLUSIONS: Reducing cold ischemia time is of great importance, because concentrations of ischemic metabolites continuously increase in renal grafts. Furthermore, small kidney grafts from growing individuals are more resistant to cold ischemia but more susceptible to warm ischemia. In the setting of donation after circulatory death with prolonged warm ischemia, ongoing catabolism in the potential renal graft may be measured by microdialysis to achieve optimal timing of transplantation.

[Inpatient pain consultation service at a university hospital: a retrospective analysis of patient characteristics and the rate of the implementation of recommendations]. / Stationäre Schmerzkonsile einer universitären Schmerzambulanz : Eine retrospektive Analyse der Patientencharakteristika und der Umsetzungsrate der Empfehlungen.

BACKGROUND: The aim of this study was to conduct an audit of a university inpatient pain consultation service and to examine the quality and the implementation of the recommended therapeutic measures. Factors that influenced the implementation should be identified. PATIENTS AND METHODS: All inpatients treated by the consultation service in the years 2009 and 2010 were analyzed retrospectively. Demographic patient characteristics as well as quality parameters of the consultation service and pharmacological and non-pharmacological recommendations and their implementation were analyzed. RESULTS: In total 1,048 requests for the consultation service were processed of which 39.7% of the requests were for patients with acute pain, 33.8% with chronic and 19.9% with tumor-associated pain. Measures recommended most were medication, physiotherapy and psychological treatment. Recommended medications were actually prescribed in more than 80%, physiotherapy recommended in about 75% and psychological treatment recommended in 47% of the cases. Only a few influencing factors for the implementation of the recommended measures could be identified. CONCLUSION: Many different pain states are seen in an inpatient pain consultation service. The recommendations given are implemented in most cases especially concerning the medication.

[Age rationing : means of resource allocation in healthcare systems]. / Altersrationierung : Mittel zur Ressourcenverteilung im Gesundheitswesen.

The necessity of limiting resource in healthcare systems is becoming increasingly more evident. The population has requirements especially in the field of healthcare which are principally unlimited. However, there are only limited financial resources which can be used to satisfy the wishes of the population. For this reason rationing models are being discussed increasingly more often. One example of these models is called age rationing which means that defined services are only offered to patients up to a particular age. The aim of this article is to discuss the model of age rationing in the context of an optimized use of resources in the healthcare system.

[Naloxone-induced pulmonary edema. Case report with review of the literature and critical evaluation]. / Naloxoninduziertes Lungenödem. Fallbericht mit Literaturübersicht und kritischer Bewertung.

A case of pulmonary edema after the administration of naloxone for laparoscopic splenectomy is reported. Previous reports of naloxone-induced pulmonary edema are listed and reviewed. The clinical course is compared to other forms of non-cardiogenic pulmonary edema. Uncertainty remains about the underlying pathophysiological process and the true impact of naloxone on the development of pulmonary edema.

Mayak workers study cohort. An inter-institutional comparison of causes of death in the cause-of-death register of Ozyorsk in the Russian Federation.

BACKGROUND: The cause-of-death register at the Southern Urals Biophysics Institute (SUBI), Ozyorsk, Russia, was established to document the number and causes of deaths in the Mayak workers cohort, which includes all persons (N = 22,377) employed at Mayak nuclear facility between 1948 and 1982. Most workers were occupationally exposed to high doses of ionizing radiation and have been shown to have increased risks of various chronic diseases including cancer. OBJECTIVES: To investigate the quality of cause of death coding in the SUBI register. METHODS: A random sample of 246 deaths (~1% of the total) was coded independently at the SUBI and the Danish Cancer Society using the International Classification of Diseases 9 (ICD-9). Proportions of matching codes were calculated. RESULTS: Overall, 233 deaths (95%) were identically classified using the ICD-9 main category matching. Excluding mismatches that were considered to be incorrectly coded during validation, the validity of the register increased to 98%. Using the specific ICD-9 first three-digit matching, 182 deaths were identically coded (74%) and the respective validity of the register was 85%. There were also some non-resolvable discrepancies demonstrating limitations of assigning one code for each death or using language-adapted ICD-9 version. CONCLUSIONS: This validation study was an important quality check of a register used for mortality follow-up in a highly influential epidemiological study on radiation-related health effects. The results of the inter-institutional comparison were generally favourable; however, since the comparison revealed individual mismatches and some systematically differing coding practices, it is essential to repeat it on a regular basis in order to maintain a high quality.

Whole-exome sequencing of pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.

[Preventive crisis management in general outpatient palliative care - prospectively cross-sectional study of General Practitioners in Eastern Bavaria]. / Vorbeugendes Krisenmanagement in der allgemeinen ambulanten Palliativversorgung. Prospektive Querschnittstudie bei Hausärzten in Ostbayern.

BACKGROUND: General out-patient palliative care (GOPC) must be integrated into the care of patients with life-limiting diseases. Aim of the study was to evaluate experiences of general practitioners concerning advance directives and palliative emergency sheets. METHODS: A self-provided survey was mailed to all general practitioners in Regensburg (cross-sectional study). Main outcome measures included responses regarding a palliative emergency sheet (PES) and a palliative emergency plan (PEP). The investigation period was four months. The analysis was performed using defined criteria (e. g. professional experience concerning palliative care patients, patients treated in nursing homes, patients with dementia). RESULTS: Sixty-nine questionnaires from 259 were analysed (response rate 27 %). 86 % of respondents named practical experience in the care of palliative patients, 46 % named theoretical knowledge in this field. 41 % and 40 % consider creating an advance directive for their practical work as important/very important (p = 0.004 concerning the treatment of more than five palliative care patients per three months). 52 % and 49 % regard a PES or a PEP to be relevant (PES median: 6.5, SD ± 2.7; PEP median: 6.5 SD ± 2.9; inter-group analysis p < 0.05). 94 % of respondents name the general practitioner to be suitable for creating an advance directive. CONCLUSION: In Germany, GOPC in end-of-life care is very important. This study shows that advance directives were declared as an important instrument for patients? autonomy. The sense of PES and PEP to ensure patients? autonomy, especially for acute emergency medical palliative care, must be better recognized. However, the increase in acceptance in the GOPC for such instruments must be disclosed. Further studies to investigate this problem are necessary.

[Physicians' knowledge on cancer pain therapy : Comparison of palliative care and prehospital emergency physicians in training]. / Wissen verschiedener Arztgruppen über die Tumorschmerztherapie : Vergleich angehender Palliativ- und Notfallmediziner.

BACKGROUND: Palliative care needs a high level of expertise. In particular, there are some potential difficulties in the treatment of patients with the symptom cancer pain (for example lack of education). In Germany, various physicians are involved in cancer pain treatment but in general palliative care patients are treated by a physician who is educated in palliative medicine. In special circumstances prehospital emergency physicians and other physicians are involved in therapy decisions in palliative care patients as well. The authors surveyed different groups of physicians in Germany about their specific knowledge of cancer pain management. MATERIAL AND METHODS: A self-designed, standardized questionnaire (50 items) was given to palliative physicians in training (PP). The survey asked prospectively for knowledge on the World Health Organization (WHO) step ladder of cancer pain therapy. The results were retrolectively compared with an earlier investigation with the same background (emergency physicians in training EP). RESULTS: There was a 99.5% response rate with a total of 654 respondents (PP 185, EP 469) and 461 (70.5%) of the respondents had knowledge of the WHO step ladder for the treatment of cancer pain [PP 164/185 (88.6%), EP 297/469 (63.3%), PP versus EP p < 0.001)]. The correct numbers of therapeutic levels were known by 361/461 participants [PP 151/164 (92.1%), EP 210/297 (70.7%), p < 0.001].The EPs with a professional experience less than 5 years answered statistically significantly more questions correctly (p = 0.004). Concerning the defined parameters knowledge and professional experience, there was no statistically significant difference in the group of PP. CONCLUSIONS: The results of this study verified that the highest knowledge scores were achieved by PPs and overall, the knowledge scores showed an improvement in comparison to previous investigations. In recent years there seems to have been an improvement in education on pain treatment,for example during medical school. Whether this also leads to an improvement of patient care and the relevance of these data for the clinical practice needs to be investigated in further studies.

[Anesthesiology and palliative medicine. Structured results of a prospective questionnaire-based survey in German hospitals]. / Anästhesiologie und Palliativmedizin. Strukturelle Ergebnisse einer prospektiven Umfrage in deutschen Kliniken.

BACKGROUND: Anesthesiology departments were often integrated into the primary formation of palliative activities in Germany. The aim of this study was to present the current integration of anesthesiology departments into palliative care activities in Germany. METHODS: The objective was to determine current activities of anesthesiology departments in in-hospital palliative care. A quantitative study was carried out based on a self-administered structured questionnaire used during telephone interviews. RESULTS: A total of 168 out of 244 hospitals consented to participate in the study and the response rate was 69%. In-hospital palliative care activities were reported for most of the surveyed hospitals. Only two hospitals in the maximum level of care reported no activities. Participation in these activities by anesthesiology departments was described in up to 92%. Historically, most activities are due to the commitment of individuals, whereas the development of palliative care of cancer pain services and hospital support teams took place in the university hospitals by 2005. CONCLUSIONS: Until 2005 many university palliative care activities had their origins in cancer pain services. These were often integrated into anesthesiology departments. Currently, anesthesiology departments work as an integrative part of palliative medicine. However, it appears from the present results that there is a domination of internal medicine (especially hematology and oncology) in palliative activities in German hospitals. This allows the focus of palliative activities to be formed by subjective specialist interests. Such a state seems to be reduced by the integration of anesthesiology departments because of their neutrality with respect to faculty-specific medical interests. Advantages or disadvantages of these circumstances are not considered by the present investigation.

Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD.

Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the ß(2)-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 µg q.d. (n=797) or tiotropium 18 µg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on "trough" (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; p<0.001) and St George's Respiratory Questionnaire (SGRQ) total score (least squares means 37.1 versus 39.2; p<0.001; raw mean change from baseline -5.1 versus -3.0), and were significantly more likely to achieve clinically relevant improvements in these end-points (indacaterol versus tiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both p<0.001). Adverse events were recorded for 39.7% and 37.2% of patients in the indacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis. Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.

Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison.

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting ß(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily ß(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 µg once daily), salmeterol (50 µg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 µg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 µg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.