International recommendations for outpatient palliative care and prehospital palliative emergencies - a prospective questionnaire-based investigation.

BACKGROUND: To determine the international recommendations and current practices for the treatment and prevention of palliative emergencies. The primary goal of the study was to gather information from experts on their nationally practised concepts. METHODS: One hundred and fifty self-report surveys were distributed by email to selected leading experts (palliative and emergency medical care) in Europe, North and South America, Africa, Asia, and Australia. An expert in this context was defined as an author of an article that was ranked by three reviewers as relevant to outpatient palliative and emergency medical . RESULTS: The total response rate was 61% (n = 92 experts). Survey responses were obtained from 35 different countries. The following standards in the treatment of palliative emergencies were recommended: (1) early integration of "Palliative Care Teams" (PCTs) and basic outpatient palliative care systems, (2) end-of-life discussions, (3) defined emergency medical documents, drug boxes, and "Do not attempt resuscitation" orders and (4) emergency medical training (physicians and paramedics). CONCLUSIONS: This study detected structurally and nationally differences in outpatient palliative care regarding the treatment of palliative emergencies. Accordingly, these differences should be discussed and adapted to the respective specifications of individual single countries. A single established outpatient palliative emergency medical care concept may be the basis for an overall out-of-hospital palliative care system.

Post-mortal bereavement of family caregivers in Germany: a prospective interview-based investigation.

BACKGROUND: Care aspects of outpatient palliative-care teams involve the medical, psychological, and spiritual needs of patients and their caregivers. The objective of our study was to examine the post-mortal bereavement of family caregivers. METHODS: The investigation was based on interviews with 50 family caregivers of 50 palliative-care patients assessed by a palliative-care team. Each caregiver was interviewed using interview sheets (mixed method designs) in accordance with three groups of validated criteria for complicated grief: Prigerson, Horowitz, and ICD-10. RESULTS: Forty-six family caregivers of terminally ill patients participated in the study. Complicated grief existed in up to 30% of the caregivers, based on the three sets of criteria. There was no significant difference (P > 0.05) among the three groups and no significant differences were found (P > 0.05) in relation to age, sex, psychosocial distress, primary cancer disease, and duration of illness or quality of care. Overall, 97% of the care-giving relatives were satisfied with the help given by the palliative-care team. CONCLUSION: The results of the study suggest that care from a specialized palliative-care team providing psychological and social support may reduce the risk of complicated grief. Careful exploration of possible risk factors for complicated grief is important for optimal care. Our study shows that healthcare providers play an important role in helping family caregivers to manage the multiple burdens and the grieving reaction. Family-focused grief therapy may prevent complicated grieving reactions.

Prehospital emergency treatment of palliative care patients with cardiac arrest: a retrolective investigation.

BACKGROUND: Today, prehospital emergency medical teams (EMTs) are confronted with emergent situations of cardiac arrest in palliative care patients. However, little is known about the out-of-hospital approach in this situation and the long-term survival rate of this specific patient type. The aim of the present investigation was to provide information about the strategic and therapeutic approach employed by EMTs in outpatient palliative care patients in cardiac arrest. METHODS: During a period of 2 years, we retrolectively analysed emergency medical calls with regard to palliative care emergency situations dealing with cardiac arrest. We evaluated the numbers of patients who were resuscitated, the prevalence of an advance directive or other end-of-life protocol, the first responder on cardiac arrest, the return of spontaneous circulation (ROSC) and the survival rate. RESULTS: Eighty-eight palliative care patients in cardiac arrest were analysed. In 19 patients (22%), no resuscitation was started. Paramedics and prehospital emergency physicians began resuscitation in 61 cases (69%) and in 8 cases (9%), respectively. A total of 10 patients (11%) showed a ROSC; none survived after 48 h. Advance directives were available in 43% of cases. The start of resuscitation was independent of the presence of an advance directive or other end-of-life protocol. CONCLUSIONS: Strategic and therapeutic approaches in outpatient palliative care patients with cardiac arrest differ depending on medical qualification. Although many of these patients do not wish to be resuscitated, resuscitation was started independent of the presence of advance directive. To reduce legal insecurity and to avoid resuscitation and a possible lengthening of the dying process, advance directives and/or "Do not attempt resuscitation" orders should be more readily available and should be adhered to more closely.

Out-of-hospital opioid therapy of palliative care patients with "acute dyspnoea": a retrospective multicenter investigation.

BACKGROUND: Prehospital emergency physicians (EP) are often confronted with the acute care of palliative care patients. Dyspnoea is a frequent acute symptom and its causes often differ from the generally known emergency medical causes. Till now, there have been no relevant concepts for emergency care of palliative care patients for their specific symptoms. METHODS: Over a 24-month period, the authors retrospectively investigated all out-of-hospital emergency medical services for palliative care patients with acute dyspnoea at four emergency physician support points. The evaluation of these services was followed retrospectively on the basis of the therapy carried out by the EP (Group 1: therapy with morphine and oxygen; Group 2: therapy with morphine, bronchodilator effective drugs and oxygen; Group 3: therapy with bronchodilator effective drugs and oxygen; Group 4: therapy with oxygen; Group 5: no medical treatment). Moreover, EPs were interviewed about their actions and their uncertainties in the treatment of palliative care patients. RESULTS: The diagnosis of acute dyspnoea in palliative care patients occurred 121 times (116 patients were integrated in the present investigation) within the defined period. In total, 116 patients were included (Group 1: 21, Group 2: 29, Group 3: 31, Group 4: 28, and Group 5: 7). Dyspnoea was satisfactorily treated in 41 percent of the patients (Group 1: 67 percent, Group 2: 52 percent, Group 3: 22 percent, Group 4: 18 percent, and Group 5: 71 percent). Most EPs (70 percent) revealed uncertainties in emergency medical therapy for patients at the end of life. CONCLUSIONS: The current investigation showed a significant relief of acute dyspnoea when using opioids, in contrast with the established out-of-hospital emergency medical therapy for acute dyspnoea. Therefore, opioids should be recommended for emergency medical therapy of dyspnoea in palliative care patients. Clinical studies that recommend the use of effective opioids for the treatment of dyspnoea in palliative care patients are supported by the current retrospective study. Most EPs felt uncertain in the treatment of palliative care patients. Therefore, advanced training in palliative care medicine and end-of-life care should be integrated into emergency medical training.

[Expectations of relatives concerning palliative home care]. / Erwartungen Angehöriger an die spezialisierte arnbulante Palliativversorgung.

BACKGROUND: Palliative home care gains in importance in Germany. In addition to administering pain and symptom control for patients a "Palliative Care Team" (PCT) tries to address the patients' psychosocial and spiritual needs. METHODS: Retrospective analysis of caregiving relatives' expectations of the support by a PCT. RESULTS: Most relatives expected a sufficient pain therapy and support of the PCT. Additionally they wished for further outreach afterthe death of the patient. CONCLUSION: Palliative homecare is perceived as a helpful supporting factor by the care-giving relatives of palliative patients.

Quality of out-of-hospital palliative emergency care depends on the expertise of the emergency medical team--a prospective multi-centre analysis.

BACKGROUND: The number of palliative care patients who live at home and have non-curable life-threatening diseases is increasing. This is largely a result of modern palliative care techniques (e.g. specialised out-of-hospital palliative medical care services), changes in healthcare policy and the availability of home care services. Accordingly, pre-hospital emergency physicians today are more likely to be involved in out-of-hospital emergency treatment of palliative care patients with advanced disease. METHODS: In a prospective multi-centre study, we analysed all palliative emergency care calls during a 24-month period across four emergency services in Germany. Participating pre-hospital emergency physicians were rated according to their expertise in emergency and palliative care as follows--group 1: pre-hospital emergency physicians with high experience in emergency and palliative medical care, group 2: pre-hospital emergency physicians with high experience in emergency medical care but less experience in palliative medical care and group 3: pre-hospital emergency physicians with low experience in palliative and emergency medical care. RESULTS: During the period of interest, the centres received 361 emergency calls requiring a response to palliative care patients (2.8% of all 12,996 emergency calls). Ten percent of all patients were treated by group 1; 42% were treated by group 2 and 47% were treated by group 3. There was a statistically significant difference in the treatment of palliative care patients (e.g. transfer to hospital, symptom control, end-of-life decision) as a result of the level of expertise of the investigated pre-hospital emergency physicians (p< 0.01). CONCLUSIONS: In Germany, out-of-hospital emergency medical treatment of palliative care patients depends on the expertise in palliative medical care of the pre-hospital emergency physicians who respond to the call. In our investigation, best out-of-hospital palliative medical care was given by pre-hospital emergency physicians who had significant expertise in palliative and emergency medical care. Our results suggest that it may be necessary to take the core principles of palliative care into consideration when conducting out-of-hospital emergency medical treatment of palliative care patients.

Detection of human tRNAs with antisense oligonucleotides.

Regulated expression and modification of tRNA isoacceptors may play an important role in the control of gene expression during such processes as differentiation and immune activation. However, the development of techniques for the identification and quantitation of multiple tRNA isoaccepting species has been hindered by the relative physicochemical similarity among individual isoacceptors and their high degree of post-transcriptional modification. We have used antisense DNA oligonucleotides derived from the T stem to acceptor stem region of six human tRNAs and one murine tRNA to detect individual tRNA isoacceptors in slot blots, Northern blots, and dot blots of human tRNA. This hybridization protocol was used in combination with tRNA fractionation by electrophoresis on a partially denaturing gel by reversed-phase low pressure chromatography and reversed-phase HPLC to identify multiple tRNA isoacceptors in a single sample of tRNA. Using this technique, it should be possible to monitor changes in the cellular tRNA repertoire that may be involved in the regulation of gene expression.

Identifying inhibitors of queuine modification of tRNA in cultured cells.

Altered queuine modification of tRNA has been associated with cellular development, differentiation, and neoplastic transformation. Present methods of evaluating agents for their ability to induce queuine hypomodification of tRNA are tedious, time-consuming, and not readily amenable to examining cell-type or tissue specificity. Therefore, a rapid, small-scale assay was developed to identify agents that alter queuine modification of tRNA in cultured cells. Monolayer cultures (2cm2) of Chinese hamster embryo cells depleted of queuine for 24 h were evaluated for their ability to incorporate [3H]dihydroqueuine into acid precipitable material (tRNA) in the presence and absence of potential inhibitors. Known inhibitors of the queuine modification enzyme tRNA-guanine ribosyltransferase (e.g., 7-methylguanine, 6-thio-guanine, and 8-azaguanine) were very effective in blocking incorporation of the radiolabel, and the dose-dependent results exhibited small standard deviations in independent experiments. The data indicate that the method is rapid, reliable, and potentially useful with a variety of cell types.

Inhibition of phorbol ester-mediated phenotypic changes in cultured cells by hypoxanthine.

Hypoxanthine induces the differentiation of certain transformed cells in vitro, so analyses were undertaken to determine whether this purine metabolite might influence the expression of transformed phenotypes induced in normal cells by chemical agents. Chinese hamster embryo cells and human skin fibroblasts in culture were treated with the promoting agent phorbol-12,13-didecanoate (PDD) with or without prior treatment with 3-methylcholanthrene (MCA), and various phenotypic effects were monitored. Hypoxanthine was found to inhibit significantly the formation of type III foci and the increase in saturation density observed for Chinese hamster cells treated with MCA plus the phorbol ester. Inosine and the hypoxanthine analogue allopurinol could also mediate the effect on saturation density, while xanthosine could not. An increase in the saturation density of human skin fibroblasts, which can be induced by the phorbol ester alone, was also inhibited by hypoxanthine. There was no significant effect on the growth rate or the intracellular nucleotide pools with hypoxanthine-treated cells. The results suggest that a normal purine metabolite, hypoxanthine, can modulate the expression of transformed phenotypes induced in vitro by the known tumor promotor PDD. These observations could help in elucidating the cellular basis for promotion of carcinogenesis.

Hematopoiesis and the inosine modification in transfer RNA.

Human promyelocytic leukemia (HL-60) cells were used to begin to evaluate the role in hematopoiesis of inosine biosynthesis in the tRNA anticodon wobble position; a reaction involving the enzymatic insertion of performed hypoxanthine. Dimethyl sulfoxide (DMSO) and hypoxanthine were found to induce the differentiation of HL-60 cells in a synergistic manner, and the induced differentiation was independent of changes in the purine catabolic enzymes adenosine deaminase and purine nucleoside phosphorylase. The short-term exposure of HL-60 cells to DMSO plus hypoxanthine resulted in enhanced leucine incorporation, and a model is presented showing how the inosine modification reaction in tRNA may be involved. A means by which hypoxanthine insertion into tRNA may modulate the synthesis of regulatory proteins (e.g., lymphokines and cell surface receptors) is also outlined.

Effects of quinine on K+ transport in heart mitochondria.

Quinine inhibits the respiration-dependent extrusion of K+ from Mg2+-depleted heart mitochondria and the passive osmotic swelling of these mitochondria in K+ and Na+ acetate at alkaline pH. These observations concur with those of Nakashima and Garlid (J. Biol. Chem. 257, 9252, 1982) using rat liver mitochondria. Quinine also inhibits the respiration-dependent contraction of heart mitochondria swollen passively in Na+ or K+ nitrate and the increment of elevated respiration associated with the extrusion of ions from these mitochondria. Quinine, at concentrations up to 0.5 mM, inhibits the respiration-dependent 42K+/K+ exchange seen in the presence of mersalyl, but higher levels of the drug produce increased membrane permeability and net K+ loss from the matrix. These results are all consistent with an inhibition of the putative mitochondrial K+/H+ antiport by quinine. However, quinine has other effects on the mitochondrial membrane, and possible alternatives to this interpretation are discussed.

Effect of azlocillin and piperacillin in subinhibitory and inhibitory concentrations on Staphylococcus aureus and Pseudomonas aeruginosa in broth, in serum and in the presence of human polymorphonuclear leukocytes.

The bactericidal activity of azlocillin and piperacillin was tested at concentrations of 1/4 the MIC, the MIC and four-fold the MIC agents a serum-resistant Staphylococcus aureus and a serum-resistant Pseudomonas aeruginosa strain in broth, in serum and in the presence of leukocytes. The antibacterial activity of azlocillin and piperacillin in serum against Staphylococcus aureus was slightly better than in broth (p greater than 0.05); both compounds were distinctly less active against Pseudomonas aeruginosa in serum than in broth (p less than 0.05). Both antibiotics enhanced susceptibility of Pseudomonas aeruginosa to leukocyte killing without serum (p less than 0.05), whereas leukocyte killing of Staphylococcus aureus was hardly improved even at the MIC and four-fold the MIC of both compounds. The antibacterial activity of azlocillin and piperacillin against both bacterial strains was most pronounced in the presence of leukocytes and serum. A marked bactericidal effect was achieved at 1/4 the MIC, the effect not being further significantly enhanced (p greater than 0.05) at the MIC or four-fold the MIC.