Decision making at the end of life--cancer patients' and their caregivers' views on artificial nutrition and hydration.

PURPOSE: Deciding on artificial nutrition and hydration (ANH) at the end of life (EoL) may cause concerns in patients and their family caregivers but there is scarce evidence regarding their preferences. Therefore, the aim of this study was to assess the impact of factors associated with ANH decision making. METHODS: Prospective, Cross-sectional survey. Adult patients admitted to hospital for symptoms of advanced cancer as well as their family caregivers completed a self-administered questionnaire. Items included personal views and concerns about ANH. Family caregivers additionally recorded their preference for their loved one and, if applicable, previous experience with ANH decisions. RESULTS: Thirty-nine out of sixty-five patients and 30/72 relatives responded. Higher age of the patient was significantly correlated with both the patient's and the relative's decision to forgo ANH (Kruskal-Wallis test, p < 0.01). Thirty-nine percent of patients, 37 % of relatives if deciding for themselves, and 24 % of relatives if deciding on behalf of their loved one opted against ANH; 36, 40 and 52 % preferred artificial hydration (AH) only (χ (2) test, p <0.001), while 23, 23 and 24 %, respectively, wished to receive ANH. Patients felt more confident about decisions on artificial nutrition (AN) than caregivers (T test, p < 0.05) and less concerned about adverse effects of forgoing ANH on pain, agitation and sensation of hunger and thirst (χ (2) test, p < 0.05). Satisfaction of patients with communication regarding forgoing ANH (5.0 ± 2.8 on a Likert scale from 0 to 10) correlated with their confidence (Spearman's rho, p < 0.01). A thorough consultation with the attending physician on ANH issues was the favoured source of support for 77 % of patients and 97 % of relatives. A majority of patients considered their relatives' opinion (67 %) and their own advance directives (62 %) as crucial for making ANH decisions, and 46 % of them had such a document completed. CONCLUSION: Cancer patients and their relatives have similar preferences regarding ANH at the EoL, but relatives are reluctant to withhold AH if deciding for their loved one. While patients seem to be confident with ANH decision making, their caregivers may particularly benefit from discussing ANH options to dissipate fears.

[Drug therapy of anxiety and fear in palliative care patients with cancer or other illnesses : a systematic review]. / Medikamentöse therapie der angst bei patienten mit fortgeschrittenen tumorerkrankungen bzw. Patienten in der palliativen situation : systematische literaturübersicht.

BACKGROUND: Pharmacological treatment of anxiety is an important part of drug treatment in palliative care. In this review we searched for the current evidence of pharmacological treatment of anxiety in palliative care. MATERIALS AND METHODS: A systematic search of PubMed, Embase, PsycLIT, PsycINFO, CINAHL for studies of anxiety in palliative care was carried out in January 2012. Furthermore we searched the Cochrane Library, references of literature and leading textbooks. Studies were identified and information was filled in a standardized extraction sheet. Studies have been categorized and anxiety as an endpoint determined. RESULTS: A total of four controlled studies, three uncontrolled studies, two retrospective studies, one case report, two surveys, one systematic Cochrane review and one unsystematic review were analyzed and included in this review. This indicates an overall low number of studies for the pharmacological treatment of anxiety in palliative care. According to our results, benzodiazepines are the most commonly used drugs in palliative care. However, based on our review, there is no evidence-based recommendation for the therapeutic use in palliative care. CONCLUSIONS: With the existing evidence no general recommendations for pharmacological treatment of anxiety in palliative care can be given. Even for the commonly used benzodiazepines, neuroleptics, antidepressants, antihistamines and beta blockers for the treatment of anxiety no evidence based recommendations can be made. However, these medications are commonly used to treat anxiety in other patient populations and can also be used in palliative care patients. According to our review we cannot recommend a single drug or give recommendations regarding the dosage of drugs. There is a strong need for randomized controlled trials to evaluate the effect of drug treatment of anxiety in palliative care patients. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

A review of German Scedosporium prolificans cases from 1993 to 2007.

Scedosporium prolificans is one of the most life-threatening fungal opportunistic pathogens due to its high resistance to common systemic antifungal agents. While a close relative of Pseudallescheria boydii, S. prolificans has a more limited geographic range being primarily found in Australia, USA and Spain. Infections have also been reported from several other European countries and from Chile. Twenty patients with Scedosporium prolificans infection or colonization from August 1993 to May 2007 were retrospectively reviewed in Germany. They had all been identified at or reported to the Reference Laboratory for Pseudallescheria/Scedosporium spp. in Berlin. Twelve of 13 patients with haematological disorders and/or on immunosuppressive therapy developed a fatal invasive scedosporiosis. Colonization of the respiratory tract was reported for one patient after heart-lung-transplantation, all six patients with cystic fibrosis and one with chronic sinusitis. Molecular studies of the S. prolificans isolates confirmed that parts of the 18S, the Internal Transcribed Spacer (ITS) regions and the D1/D2 domain of the 28S region of rDNA are monomorphic. However, sequencing of parts of the translation elongation factor EF1-alpha (EF-1alpha) and the chitin synthase (CHS-1) genes revealed the presence of three and two distinct genotypes, respectively. Two informative mutations were found in EF-1alpha and a single nucleotide exchange in the CHS-1 gene.

Successful treatment of disseminated mucormycosis with a combination of liposomal amphotericin B and posaconazole in a patient with acute myeloid leukaemia.

The combination of resection of infected tissue and antifungal therapy is the treatment of choice in mucormycosis. In disseminated mucormycosis, where surgery is impossible, the mortality is almost 90%. We report the first case of disseminated mucormycosis that was cured with a combination therapy of liposomal amphotericin B and posaconazole without surgical intervention.

Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients by seminested PCR assay of tissue samples.

Aspergillosis and mucormycosis are the most common mold infections in patients with hematological malignancies. Infections caused by species of the genus Aspergillus and the order Mucorales require different antifungal treatments depending on the in vitro susceptibility of the causative strain. Cultures from biopsy specimens frequently do not grow fungal pathogens, even from histopathologically proven cases of invasive fungal infection. Two seminested PCR assays were evaluated by amplifying DNA of zygomycetes and Aspergillus spp. from organ biopsies of 21 immunocompromised patients. The PCR assays correctly identified five cases of invasive aspergillosis and six cases of mucormycosis. They showed evidence of double mold infection in two cases. Both assays were negative in five negative controls and in two patients with yeast infections. Sequencing of the PCR products was in accordance with culture results in all culture-positive cases. In six patients without positive cultures but with positive histopathology, sequencing suggested a causative organism. Detection of fungal DNA from biopsy specimens allows rapid identification of the causative organism of invasive aspergillosis and mucormycosis. The use of these PCR assays may allow guided antifungal treatment in patients with invasive mold infections.

Primary cytomegalovirus infection in an outpatient setting--laboratory markers and clinical aspects.

BACKGROUND: Occasionally, primary cytomegalovirus (CMV) infection may give rise to more or less severe clinical illness in immunocompetent adults. We retrospectively analyzed cases of acute CMV infection in medical outpatients. PATIENTS AND METHODS: Over a 6-year period, we identified 22 patients with a febrile illness and hepatitis suffering from primary CMV infection. This was diagnosed on the basis of a strongly positive CMV IgM antibody test result and/or CMV IgG seroconversion. Clinical features as well as relevant laboratory results were analyzed. We also tested available samples for CMV glycoprotein B-specific antibodies and CMV IgG avidity and analyzed results of Epstein-Barr virus (EBV)-specific antibody assays. In addition, current age-specific CMV IgG seroprevalence rates were determined using 9,870 routine patient samples. RESULTS: At presentation, all patients complained of malaise and fever higher than 38 degrees C, and many also complained of cephalgia. Most patients who underwent abdominal ultrasonography had an enlargement of the spleen. Most patients had a relative lymphocytosis but only three had a mild leukocytosis. C-reactive protein was only slightly elevated in 13 patients; all 22 patients had elevated levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Half the patients reported travel to areas outside western Europe, mostly to tropical and subtropical areas, within 3 weeks before onset of illness. Primary CMV infection was confirmed by negative anti-gB antibody test results and the absence of high-avidity CMV antibodies. In contrast, despite past EBV infection demonstrated by positive anti-EBNA-1 results, 15 out of 21 patients tested for EBV markers had positive or nonspecific IgM test results. The overall CMV IgG seroprevalence rate in the routine samples was 64.4%, with marked age-dependent increases. CONCLUSION: CMV is a relevant differential diagnosis in feverish illnesses accompanied by hepatitis in otherwise healthy adults, about 40% of whom are CMV-naïve. Half our patients seem to have acquired their CMV infection abroad, so that a diagnosis of CMV infection needs to be taken into account in travelers, in addition to infectious illnesses more commonly considered in this context, such as dengue or hepatitis A. For diagnosis, both CMV and EBV antibody studies should be performed and the inclusion of assays able to demonstrate past infection is helpful for achieving a definite diagnosis.

Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis.

Aspergillus fumigatus is often found in the respiratory tract secretions of patients with cystic fibrosis (CF), although the role of the fungus for progression of pulmonary disease remains unclear. This study aimed to investigate the frequency of A. fumigatus and other fungi in sputum of adult CF patients using different methods for culture and microscopy. Results from the analysis of 369 samples from 94 patients showed that A. fumigatus could be isolated in 45.7% of patients. Other moulds were rare, but the yeast Candida albicans was another frequent isolate, detected in 75.5% of patients. A comparison of different culture media showed no difference between a selective medium developed to specifically inhibit Pseudomonas aeruginosa and a standard fungal culture medium for growth of A. fumigatus, although both were more efficient for detection of fungi than other bacterial culture media. Fluorescent microscopy with calcofluor white was more sensitive for detection of fungal hyphae in undiluted sputum than standard methylene blue staining. This study shows that A. fumigatus and C. albicans have a high frequency in adult CF patients. Microbiological analysis should routinely include methods for specific identification of fungi to monitor for potential complications arising from fungal disease in these patients.

Clinicopathological features of cutaneous histoplasmosis in human immunodeficiency virus-infected patients in Zimbabwe.

Reports of disseminated Histoplasma infection in African AIDS patients are scanty. In Zimbabwe, 12 patients presented in 1994-2000 with facial nodular/papular cutaneous lesions, which became umbilicated and finally ulcerated. Histology revealed non-granulomatous inflammation and macrophages stuffed with Histoplasma. Recognition of these clinical features may lead to more rapid diagnosis of disseminated histoplasmosis in Africa.

Diagnosis of disseminated zygomycosis using a polymerase chain reaction assay.

Invasive pulmonary zygomycosis is an uncommon opportunistic infection in patients with haematological malignancies. Clinical manifestations are in distinguishable from the more frequent invasive aspergillosis. Standard diagnostic methods like culture and microscopy from respiratory secretions have a low diagnostic sensitivity. A case in which proven invasive pulmonary zygomycosis was confirmed using a panfungal polymerase chain reaction assay in blood is presented. Since zygomycosis requires more aggressive treatment than aspergillosis (high-dose amphotericin B and surgical intervention), the polymerase chain reaction assay may improve the outcome of these often fatal infections by guiding the therapeutic approach through an early, non-invasive diagnosis.

Influence of antimicrobial treatment on mortality in septicemia.

OBJECTIVE: To determine the influence of antimicrobial therapy and of predisposing illness on the septicemia mortality rate. METHOD: All blood-culture-positive episodes of septicemia in the Department of Medicine at the University Hospital in Frankfurt between 1989 and 1993 were entered on a database. Underlying illnesses were classified as immunocompromising diseases (hematological malignancies, AIDS and others), severe chronic and chronic illnesses and no predisposing illnesses. Therapy was judged on the basis of the in-vitro-susceptibility of the organism ('appropriate') and the interval (no. of days) between the onset of septicemia and start of appropriate treatment noted. For mortality all deaths within 28 days after the onset of septicemia were counted. RESULTS: Overall mortality due to septicemia was 18.1%, ranging from 9.4% (organ transplantation) to 50% (liver cirrhosis) according to the underlying illness. Mortality in patients receiving appropriate treatment (83.1%) was 16% as opposed to 28%, if no appropriate treatment was given (p<0.001). Comparison of appropriate treatment started within and after 48 hours revealed a reduction in mortality from 30.9% to 15.4% for early appropriate therapy in patients with hematological malignancies (p<0.002). For septicemia in patients with AIDS and chronic illnesses mortality was significantly higher (p<0.05) if treatment remained inappropriate (AIDS 28.6%, chronic illness 33.3%), but was similar when early and delayed appropriate therapy were compared (AIDS: 13% vs. 12.8%, chronic illness 11.8% vs. 11.1%). CONCLUSION: First-line treatment regimens for septicemia in patients with hematological malignancies should include the greatest possible part of the spectrum of causative organisms. In contrast to that it may be acceptable to rely to some extent on a change of treatment, when treating septicemia in patients with chronic illnesses or AIDS. These considerations are of value in the debate on rising health care costs. Several other facts, such as the stable mortality rate of 8 - 12% in previously healthy patients and the range of mortality from 9.4 - 50%, if predisposing illnesses are present, indicate the existence of adverse factors influencing the outcome of septicemia in spite of appropriate therapy. These pathophysiological factors will have to be studied in detail in order to improve the prognosis of septicemia further.

Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies.

The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of systemic mycoses was investigated in granulocytopenic patients with haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic efficacy, and 214 for adverse events. Patients with similar characteristics receiving oral amphotericin B as antifungal prophylaxis, observed over 15 months before introduction of itraconazole, served as control group (n = 223). With itraconazole prophylaxis, 13 cases of aspergillosis (9 proven, 1 probable, 3 possible; 7%) and no systemic yeast infection occurred, compared with 14 episodes of aspergillosis (9 proven, 2 probable, 3 possible; 6%) and 3 proven systemic yeast infections (Candida albicans, Candida norvegensis, Trichosporon beigelii) in the historical group. Adverse events were observed in 13% of evaluable patients receiving itraconazole. In four patients with acute lymphoblastic leukaemia receiving itraconazole and vincristine simultaneously, severe vinca alkaloid-induced neurotoxicity occurred. Plasma concentrations of itraconazole and hydroxyitraconazole were measured in 64 patients. After eight days of itraconazole the median drug concentration was adequate (700 ng/mL), but there was a marked individual variation (229-2861 ng/mL). In comparison with a historical group, antifungal prophylaxis with itraconazole reduced the incidence of systemic yeast infections, but the frequency of aspergillosis was similar. However, a general increasing incidence of aspergillus infections at our hospital over the last four years should be considered in the assessment of study results.