Relationship between ecological condition and ecosystem services in European rivers, lakes and coastal waters.

We quantify main ecosystem services (i.e. the contribution of ecosystems to human well-being) provided by rivers, lakes, coastal waters and connected ecosystems (riparian areas and floodplains) in Europe, including water provisioning, water purification, erosion prevention, flood protection, coastal protection, and recreation. We show European maps of ecosystem service capacity, flow (actual use), sustainability and efficiency. Then we explore the relationship between the services and the ecosystem condition at the European scale, considering the ecological status of aquatic ecosystems, reported under the EU Water Framework Directive, as a measure of the ecosystem integrity and biodiversity. Our results indicate that a higher delivery of the regulating and cultural ecosystem services analysed is mostly correlated with better conditions of aquatic ecosystems. Conversely, the use of provisioning services can result in pressures on the ecosystem. This suggests the importance of maintaining good ecological condition of aquatic ecosystems to ensure the delivery of ecosystem services in the future. These results at the continental scale, although limited to the ecosystem services under analysis, might be relevant to consider when investing in the protection and restoration of aquatic ecosystems called for by the current EU water policy and Biodiversity Strategy and by the United Nations Sustainable Development Goals.

Cutaneous lumbosacral Herpes simplex virus among patients hospitalized for an advanced disease.

BACKGROUND: Cutaneous Herpes simplex virus (HSV) infections are regularly observed in lumbosacral areas, and many are refractory to appropriate initial diagnosis and management. OBJECTIVE: We aimed to evaluate the incidence of lumbosacral HSV among advanced disease patients, to estimate their survival index from HSV onset, and to describe their clinical and virological characteristics. METHODS: A prospective, descriptive study was conducted in a palliative and continuous care centre, collecting patients with suspected cutaneous HSV lesions in the lumbosacral area. RESULTS: From 2008 to 2010, 24 patients were included: 19 had HSV-2 confirmed by at least one laboratory test. Incidence of HSV-2 was 2.67% (1.73-4.33%, 95% CI). No age, gender or survival differences were observed compared to the global population in the centre. Most lesions were detected early as vesicles (14/24) or small ulcers. Sensitivity was good for all diagnostic methods (62.5% for immunofluorescence and 79.2% for culture and/or PCR). Outcome was favourable under classical antiherpetic drugs and topical antiseptic dressing. CONCLUSIONS: Cutaneous lumbosacral HSV remains uncommon in patients hospitalized with advanced diseases. Most of these patients suffer from pressure ulcers or other dermatitis; we advocate increased attention of this diagnosis to avoid skin complications and added pain.

Frail old patients as a target population for cancer trials.

The recent distinction between co-morbidity and multi-morbidity well stresses the difficulty of managing old patients with cancer whose complexity is not captured by a list of diagnoses or biological burden alone. The most adequate answer found by oncologists and geriatricians was to work together for better evaluating the physiological age and body reserve of the patient. The gold standard tool to assess old patient with cancer is named Comprehensive Geriatric Assessment. Its systematic application needs geriatric competences and time. In this context, a great number of cancer patients are considered as "frail" because they have reduced available physiological reserves. They might not withstand stress when challenged. Oncologists and geriatricians have imagined an innovative process to change the screening procedure of these patients, determine the prognosis, adapt the treatment strategy, to increase the patient's survival and his/her quality of life. The internet website "www.clinicaltrials.com" only lists 8 studies focused on frail elders with cancer. Six of them are focused on specific cancers or specific treatments, one was applied to all kind of cancers and the last was an opinion overview from oncologists and geriatricians. The selection criteria of frail patients are very diverse and probably include cancer patients who are not comparable. It is now time to try to identify new practical, reliable and accurate tools to facilitate the inclusion of the same kind of patients suffering from the same kind of cancer to be able to give more appropriate care and at the same time to constitute a valuable data base. Existing tools are reviewed and analyzed.

Role of advance directives in palliative care units: a prospective study.

Advance directives (ADs) might be useful in achieving improved communication and satisfaction with decision making at the end-of-life. Our aims were to better characterise patients with advanced oncological disease who decided to complete ADs and to measure the effect of ADs completion on the satisfaction level with end-of-life care from both patients and their relatives. A prospective study was conducted in three palliative care units. Patients with advanced cancer were included if they met the following criteria: an estimated life expectancy of <6 months, fluency in French, Mini Mental State Examination >20 and not yet completed ADs. All the patients received information about ADs and decided whether to complete ADs or not. The level of satisfaction with involvement in the decision process concerning end-of-life care was assessed by means of a written questionnaire. In all, 53 of 228 patients were included, and 12 decided to complete ADs. Patients who completed ADs had statistically less depression one week after inclusion (P = 0.030), had a lower anxiety score on the second week and had a lower depression score on the third week. There was a trend towards a higher satisfaction level with the involvement of the patients in end-of-life care for those completing ADs (P = 0.878). In conclusion, each patient with an advanced progressive disease should be informed about ADs and be encouraged to complete the ADs with the aim to ease many fears as well as to improve communication.

Palliative care education in Swiss undergraduate medical curricula: a case of too little, too early.

Palliative medicine education is an important strategy in ensuring that the needs of terminally ill patients are met. A review was conducted in 2007 of the undergraduate curricula of all five of Switzerland's medical schools to identify their palliative care-related content and characteristics. The average number of mandatory hours of palliative care education is 10.2 h (median 8 h; range 0-27 h), significantly short of the 40 h recommended by the European Palliative Care Association's Education Expert Group. The median time allocated to designated palliative care blocks is 3 h (range 0-8 h). Most of the education occurs before the clinical years, and there are no mandatory clinical rotations. Three schools offer optional clinical rotations but these are poorly attended (<10% of students). Although a number of domains are covered, ethics-related content predominates; 21 of a total of 51 obligatory hours (41%). Communication related to palliative care is largely limited to 'breaking bad news'. In two of the schools, the teaching is done primarily by palliative care physicians and nurses (70% or more of the teaching). In the others, it is done mostly by educators in other clinical specialties and ethics (approximately 90% of the teaching). These findings show significant deficiencies.

[Competencies in palliative care: what should the physicians be able to do?]. / Compétences en soins patiatifs: que faut-il savoir faire en tant que médecin?

Palliative patients (patients with progressive incurable illnesses) have a number of needs, early and late in their illness trajectories. This article highlights some of the most important competencies required by physicians to address these needs. They cover a broad spectrum of domains and include pain and symptom management, communication, disclosure, prognostication, and psychological, social and spiritual needs. All physicians, generalists and specialists alike, should possess the basic competencies but should also recognize that some patients, especially those not responding to initial strategies, require timely referrals to specialized palliative care teams.

Organization of the clinical activity of geriatric oncology: report of a SIOG (International Society of Geriatric Oncology) task force.

Management for elderly cancer patients world wide is far from being optimal and few older patients are entering clinical trials. A SIOG Task Force was therefore activated to analyze how the clinical activity of Geriatric Oncology is organized. A structured questionnaire was circulated among the SIOG Members. Fifty eight answers were received. All respondents identified Geriatric Oncology, as an area of specialization, however the organization of the clinical activity was variable. Comprehensive Geriatric Assessment (CGA) was performed in 60% of cases. A Geriatric Oncology Program (GOP) was identified in 21 centers, 85% located in Oncology and 15% in Geriatric Departments. In the majority of GOP scheduled case discussion conferences dedicated to elderly cancer patients took regular place, the composition of the multidisciplinary team involved in the GOP activity included Medical Oncologists, Geriatricians, Nurses, Pharmacists, Social Workers. Fellowships in Geriatric Oncology were present in almost half of GOPs. Over 60% of respondents were willing to recruit patients over 70 years in clinical trials, while the proportion of cases included was only 20%. Enrolment in clinical trials was perceived as more difficult by 52% and much more difficult in 12% of the respondents. In conclusion, a better organization of the clinical activity in Geriatric Oncology allows a better clinical practice and an optimal clinical research. The GOP which can be set up in the oncological as well as in the geriatric environment thought a multidisciplinary coordinator effort. Future plans should also concentrate on divisions, units or departments of Geriatric Oncology.

[Sensible anticancer treatment in the very old]. / Traitement oncologique raisonnable du patient agé.

Significant numerical increase of elderly people augments in parallel the number of geriatric oncological situations. It is thus necessary to bridge between two apparently divergent worlds. This will allow to look at and evaluate the elderly cancer person with the accuracy of the specialist while remaining at the appropriate distance ordered by the geriatrician eye. It becomes then possible to undertake diagnostic and therapeutic manoeuvres in the respect of everybody's individuality. This contributes to maintain the best quality of life possible until the end. Pater(mater)nalism is to be abandoned and knowledge is to be shared. Daily interdisciplinarity, humanitarian spirit and ethical sensibility are essentials tools to make this enterprise a success.

Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine) by subcutaneous bolus injection: a phase II study.

BACKGROUND: To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria. RESULTS: Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 x 10(9)/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed. CONCLUSIONS: One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.

Response and palliation in a phase II trial of gemcitabine in hormone-refractory metastatic prostatic carcinoma. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: In a phase II trial, 43 patients with hormone-refractory prostate cancer were treated with gemcitabine at a dose of 1,200 mg/m2 over 2 hours (later decreased to 1,000 mg/m2 due to hematological toxicity) on days 1, 8 and 15 of a 28 day cycle. PATIENTS AND METHODS: Inclusion criteria were proven tumor progression after hormonal treatment and increased PSA levels, a WHO PS < or = 2, adequate bone marrow reserve, liver and renal function and age < or =, 80 years. Response criteria were based on PSA levels (CR: normalization of PSA, PR: > 50% decrease). Quality of life (QL) was assessed with the EORTC QLQ-C30 on day 1 of each treatment cycle and on day 8 of the first cycle (range of scales 0-100). Physician-rated pain intensity and use of pain medication were assessed at the same timepoints. RESULTS: Hematological toxicity of gemcitabine led to a dose-reduction in 48% of all cycles. Three of forty-three patients (RR = 7%) showed a PSA response: one CR and three PR with time to treatment failure of 8.7, 6.6 and > or = 9.3 months. Seven patients (16%) had stable disease (NC) for a median duration of 7.1 months (range 6.1-11.7 months). There was one case with objective regression of lymph node metastases. Patients reported a considerably impaired health status/QL (n = 41, median = 50) and severe fatigue (n = 41, median = 55.6) at baseline, with no change under treatment. Pain (QLQ-C30) was also severe at baseline (N=41, median=50) but was improved at the end of cycles 1 (n = 33, median change = -16.7, P = 0.0002), 2 (n = 19, median change = -33.3, P = 0.0006), 3 (n = 14, median change = -16.7, P = 0.06) and 4 (n = 9, median change = -33.3, P = 0.04). Patient-rated pain and use of analgesics as combined endpoint yielded palliation for at least 8 weeks in 14 patients (32%). Nine of these patients showed at least stable disease (CR/PR or NC by PSA level), five indicated a benefit in spite of progressive disease. CONCLUSIONS: Gemcitabine in the dose and schedule indicated above has a significant beneficial impact on pain in patients with hormone-refractory prostatic carcinoma despite its limited activity in terms of PSA response and considerable, especially hematological, toxicity.

Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies.

The feasibility of combining cladribine with cyclophosphamide and prednisone in the management of indolent lymphoid malignancies was determined. Nineteen patients [nine chronic lymphocytic leukaemia (CLL), seven non-Hodgkin's lymphoma (NHL) and three macroglobulinaemia (M))] received cladribine 0.1 mg kg(-1) per day as a subcutaneous bolus injection on days 1-3 (up to 5 injections) with intravenous cyclophosphamide 500 mg m(-2) on day 1 and oral prednisone 40 mg (m-2) on days 1-5 at 4-weekly intervals up to a maximum of six courses. A total of 80 courses were given. Overall response rate was 88%, with four patients achieving a complete clinical and haematological response and 12 achieving a partial response. Neutropenia WHO grade 4 in two patients and WHO grade 3 infection in one patient were the limiting toxicities on treatment. During the follow-up, WHO grade >3 haematological complications occurred in five patients and WHO grade >3 non-haematological complications in five patients. There were no treatment-related deaths. This study demonstrates the feasibility of the cladribine/cyclophosphamide/prednisone (CCP) combination that appears highly active and safe in the management of indolent lymphoid malignancies.

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia. Swiss Group for Clinical Cancer Research (SAKK).

PURPOSE: To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL). PATIENTS AND METHODS: In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response. RESULTS: A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P < or = 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%-52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1-4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1. CONCLUSION: Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.