Homeopathy as Praxis: Integration of Homeopathy as Supportive Care into Daily Life in Early Breast Cancer Patients.

INTRODUCTION: Homeopathy is one of most widely used non-conventional supportive care methods used by women with breast cancer. This article aims to describe the routines and practices related to homeopathy as supportive care used by women with non-metastatic breast cancer in France. METHODS: This qualitative study used Grounded Theory. Participants were women with early breast cancer and healthcare professionals (General Practitioner homeopaths & oncologists). Inclusion depended on specific criteria and the aim of theoretical sampling until data saturation. Data were collected through individual semi-structured interviews and focus groups following evolving topic guides. Transcribed interviews underwent in-depth thematic analysis. Inclusion, interviewing, transcription and coding occurred iteratively. Data was reported according to COREQ guidelines. RESULTS: The therapeutic agency of homeopathy was distributed to different actors and ritualized material activities highly involving the patient. The choice of remedy was mostly delegated by patients to General Practitioner homeopaths (GPH) during consultations. Individualization, that is to say adaptation to the patient, differed from other modes of access to homeopathy (self-medication and oncologists). Self-medication was mostly limited to known products in a limited time frame. However, we identified a supported self-medication using trusted homeopathic protocols. Following homeopathic prescriptions involves a high level of commitment on behalf of the patient and follows different rules for homeopathy intake. This knowledge was either acquired earlier for users or discovered along breast cancer treatment for non-users. Taking homeopathy involved small daily actions for intake of different products at different times of the day. New users used strategies to ease the integration of homeopathy into their daily life. The stance toward such rules differed among patients. Some followed rules to optimize their effects while others simplified the rules and took those rituals as part of homeopathy benefits. CONCLUSION: Homeopathy as supportive care in breast cancer is distributed toward different actors and ritualized activities. Homeopathy is a supported practice where GPH played a role in the prescription. Health Literacy in homeopathy played a role to ease its integration into daily life and identify the potential benefits. The high involvement of patients in their homeopathic treatment is a form of treatment reappropriation and empowerment.

Element mobility related to rock weathering and soil formation at the westward side of the southernmost Patagonian Andes.

Rock weathering and pedogenesis are fundamental processes for element mobility in terrestrial bio-geochemical cycles and for the regulation of primary productivity in adjacent coastal marine ecosystems. Here, soils developed from volcanic ash under extreme climate conditions could play a particular role. We therefore investigated rock weathering, soil formation and the associated mobilization of trace elements and micronutrients in a pristine South Patagonian ecosystem. Weathered and unweathered basement lithologies, tephra of the 4.216 kyrs BP Mt. Burney eruption and four soil profiles are considered. The approach combines mineralogical (XRD, SEM) and inorganic geochemical (XRF, ICP-OES/MS) with organic geochemical analyses (TOC, TN, δ13C, δ15N, DOC extracts) of representative samples. Chemical weathering is quantified by mass balance calculations and 14C age constraints allow a correlation of pedogenic processes with the paleoenvironmental history of the area. Our data document that pedogenesis with initial peat formation occurred since ~2.5 kyrs BP. In these acidic peaty Andosols, intensive alteration of volcanic glass mobilized large quantities of elements, considerably surpassing leachates provided by basement rock weathering. Clay production is limited in favor of the formation of amorphous Al- and crystalline Fe-(hydr)oxides. However, tephra alteration, soil organic matter turnover rates, enhanced dissolved organic carbon export, and Fe-/Al-(hydr)oxide precipitation are closely linked and ultimately controlled by rainfall-induced water-level fluctuations, highlighting the dominant influence of the southern westerly wind belt. The transport of mobilized trace elements and micronutrients adsorbed onto suspended colloids (dissolved organic carbon, Al-humus complexes and Fe-(hydr)oxides) is redox-pH-dependent, highly variable and ultimately regulated by westerly intensity. Broader implications of this work include a new perspective on the climate-controlled micronutrient delivery for primary productivity in South Patagonian fjords, which is strongly affected by Andosol formation. Furthermore, a careful evaluation of 'ordinary' geochemical proxies in regional paleoenvironmental archives is needed to account for these unique pedogenic processes.

Observational, prospective, phase 4 study in patients with first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and platinum-based therapy: DIRECT.

BACKGROUND: Cetuximab plus platinum-based therapy (PBT) followed by cetuximab maintenance until progression (EXTREME) is a guideline-recommended first-line treatment option in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). DIRECT (Dose Intensity RElative to CeTuximab) was the first phase 4 observational study evaluating EXTREME administration in the real-world setting. AIMS: The primary aim of this study was to assess the relative dose intensity of cetuximab in patients with R/M SCCHN treated with first-line cetuximab according to the EXTREME regimen. METHODS AND RESULTS: Patients were ≥18 years old and eligible to receive cetuximab/PBT. Primary endpoint was cetuximab relative dose intensity (RDI). Of prospectively enrolled patients (n = 157), 119 received ≥1 cycle of EXTREME. Practices differing from the EXTREME trial were 5-fluorouracil omission (14%), maintenance cetuximab given every other week (54%), prior cetuximab, disease-free interval <6 months. 64% of patients reached cetuximab RDI ≥80%; mean cetuximab RDI was 88%. 46% of patients received maintenance cetuximab (mean RDI, 91%). Median progression-free survival and overall survival were 4.5 and 9.4 months. No new/unexpected safety findings were observed. CONCLUSIONS: The DIRECT study showed that first-line cetuximab plus PBT was a feasible, beneficial first-line treatment regimen in patients with R/M SCCHN in the real-world setting.

Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 1. THR-149.

Intravitreal (IVT) injection of pharmacological agents is an established and widely used procedure for the treatment of many posterior segment of the eye diseases. IVT injections permit drugs to reach high concentrations in the retina whilst limiting systemic exposure. Beyond the risk of secondary complications such as intraocular infection, the potential of systemic adverse events cannot be neglected. Therefore, a detailed understanding of the rules governing systemic exposure following IVT drug administration remains a prerequisite for the evaluation and development of new pharmacological agents intended for eye delivery. We present here a novel mathematical model to describe and predict circulating drug levels following IVT in the rabbit eye, a species which is widely used for drug delivery, pharmacokinetic, and pharmacodynamic studies. The mathematical expression was derived from a pharmacokinetic model that assumes the existence of a compartment between the vitreous humor compartment itself and the systemic compartment. We show that the model accurately describes circulating levels of THR-149, a plasma kallikrein inhibitor in development for the treatment of diabetic macular edema. We hypothesize that the model based on the rabbit eye has broader relevance to the human eye and can be used to analyze systemic exposure of a variety of drugs delivered in the eye.

Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687.

Intravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.

A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy.

BACKGROUND: Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT3 ) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy-induced nausea and vomiting (CINV) prevention over a 5-HT3 RA plus DEX. However, studies comparing the NK1 RAs in the class are lacking. A fixed combination of a highly selective NK1 RA, netupitant, and the 5-HT3 RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long-lasting protection from CINV. This study is the first head-to-head NK1 RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS: This was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%. RESULTS: Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant. CONCLUSION: This pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA. IMPLICATIONS FOR PRACTICE: In the absence of comparative neurokinin 1 (NK1 ) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1 RA agents to be interchangeable and equivalent. This is the first head-to-head study comparing one NK1 RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single-dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard-of-care.

Does selective hormesis impact herbicide resistance evolution in weeds? ACCase-resistant populations of Alopecurus myosuroides Huds. as a case study.

BACKGROUND: A field-evolved herbicide-resistant weed population can represent a heterogeneous composite of subpopulations that differ in their susceptibility and responsiveness to herbicide hormesis. Variable hormesis responsiveness can result in selection for and against certain subpopulations under low herbicide doses, and this has the potential to contribute to the evolution of resistance. The relevance of this hypothesis at practical field rates was studied for two field-collected acetyl-coenzyme A carboxylase (ACCase) target-site resistant (TSR) biotypes of Alopecurus myosuroides Huds. (haplotype Leu1781) exposed to three ACCase inhibitors. Herbicide dose responses were evaluated at the population level and at different subpopulation levels after the dissection of individual plants by herbicide selection and genotyping. RESULTS: The practical field rates of fenoxaprop-P were lower than the observed hormetic doses in the resistant subpopulation, whereas the field rates of clodinafop and cycloxydim stimulated the shoot biomass in different resistant subpopulations by 21-38% above that of the control. Because variable dose levels induced hormesis in the different subpopulations, the practical field rates showed a significant potential to selectively enhance parts of a resistant field population, but did not impact or adversely affect other parts of the population. CONCLUSION: As a consequence of population heterogeneity, herbicide hormesis may impact resistance evolution in weeds at realistic use rates via the selective promotion of individual genotypes. However, the practical relevance of this phenomenon may be influenced by many factors, such as the herbicidal active ingredient used, as indicated in this study. © 2018 Society of Chemical Industry.

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study.

PURPOSE: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. PATIENTS AND METHODS: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: "low risk" (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus "high risk" (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. RESULTS: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. CONCLUSION: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.

BACKGROUND: How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. METHODS: This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged ≥18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0·2 to less than 2·0 µg/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. FINDINGS: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. INTERPRETATION: Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. FUNDING: French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer.

A survey of clinician attitudes and self-reported practices regarding end-of-life care in heart failure.

BACKGROUND: As heart failure often follows an unpredictable clinical trajectory, there has been an impetus to promote iterative patient-provider discussions regarding prognosis and preferences for end-of-life care. AIM: To examine clinicians' practices, expectations, and personal level of confidence in discussing goals of care and providing end-of-life care to their patients with heart failure. DESIGN: Multi-site clinician survey. SETTING AND PARTICIPANTS: Physicians, nurse practitioners, and physician assistants at Mayo Clinic (Rochester, Minnesota, USA) and its surrounding health system were asked to participate in an electronic survey in October 2013. Tertiary Care Cardiology, Community Cardiology, and Primary Care clinicians were surveyed. RESULTS: A total of 95 clinicians participated (52.5% response rate). Only 12% of clinicians reported having annual end-of-life discussions as advocated by the American Heart Association. In total, 52% of clinicians hesitated to discuss end-of-life care citing provider discomfort (11%), perception of patient (21%) or family (12%) unreadiness, fear of destroying hope (9%), or lack of time (8%). Tertiary and Community Cardiology clinicians (66%) attributed responsibility for end-of-life discussions to the heart failure cardiologist, while 66% of Primary Care clinicians felt it was their responsibility. Overall, 30% of clinicians reported a low or very low level of confidence in one or more of the following: initiating prognosis or end-of-life discussions, enrolling patients in hospice, or providing end-of-life care. Most clinicians expressed interest in further skills acquisition. CONCLUSION: Clinicians vary in their views and approaches to end-of-life discussions and care. Some lack confidence and most are interested in further skills acquisition.

Determinants of continuance intention in a post-adoption satisfaction evaluation of a clinical information system.

PURPOSE: The evaluation of end-user satisfaction is an essential part of any clinical information system (CIS) project. The purpose of this study is to evaluate the determinants of CIS continuance intention in a late post-adoption phase at the Georges Pompidou University Hospital (HEGP) in Paris. METHODS: We designed an electronic survey instrument based on an IT post-adoption model (ITPAM) developed from three previous models, i.e., the Delone and McLean Information Success Model, the Davis TAM model and the Bhattacherjee information system continuance intention model. RESULTS: 419 questionnaires were collected from CIS users directly involved in patient care. The perceived CIS quality, usefulness and user satisfaction are significantly lower for medical professions than other professional groups. Continuance intention is very high within all professional subgroups. In a multiple regression analysis, the global satisfaction (R(2) = .780) was positively and significantly correlated with CIS quality, confirmation of expectations and perceived CIS usefulness. The continuance intention (R(2) = .392) was positively and significantly correlated with perceived CIS usefulness, confirmation of expectations and global satisfaction. CONCLUSION: In a late post-adoption CIS deployment phase, continuance intention does not significantly depend on individual end user characteristics but is significantly associated with the perceived CIS usefulness, confirmation of expectations and global satisfaction.

Applicability of different hydraulic parameters to describe soil detachment in eroding rills.

This study presents the comparison of experimental results with assumptions used in numerical models. The aim of the field experiments is to test the linear relationship between different hydraulic parameters and soil detachment. For example correlations between shear stress, unit length shear force, stream power, unit stream power and effective stream power and the detachment rate does not reveal a single parameter which consistently displays the best correlation. More importantly, the best fit does not only vary from one experiment to another, but even between distinct measurement points. Different processes in rill erosion are responsible for the changing correlations. However, not all these procedures are considered in soil erosion models. Hence, hydraulic parameters alone are not sufficient to predict detachment rates. They predict the fluvial incising in the rill's bottom, but the main sediment sources are not considered sufficiently in its equations. The results of this study show that there is still a lack of understanding of the physical processes underlying soil erosion. Exerted forces, soil stability and its expression, the abstraction of the detachment and transport processes in shallow flowing water remain still subject of unclear description and dependence.

Cancer after heart transplant: implications for practice.

Cancer after heart transplant is recognized as a leading cause of morbidity and mortality. A man's clinical course after receiving a heart transplant is described, with emphasis on important clinical considerations in the care of heart transplant recipients.

Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01.

PURPOSE: To assess the benefit and toxicity and quality-of-life (QOL) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients. PATIENTS AND METHODS: Between December 1998 and June 2004, 444 patients with T1b-T3, N0 pNx, M0 prostate carcinoma were randomly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only. Patients were stratified according to the prognostic factor of lymph node involvement (LNI). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group. The pelvic dose was 46 Gy. The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy. Criteria for progression-free survival (PFS) included biologic prostate-specific antigen recurrences or a local or metastatic evolution. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective, Objective, Management, and Analytic scales, respectively. The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30, the International Prostatic Symptom Score, and the Sexual Function Index scales. RESULTS: With a 42.1-month median follow-up time, the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group. On multivariate analysis, low LNI risk and hormonal therapy were statistically associated with increased PFS. However, subgroup analyses based on these factors did not show any benefit for pelvic irradiation. There were no significant differences in acute and late digestive toxicities and in QOL outcomes. CONCLUSION: Pelvic node irradiation was well tolerated but did not improve PFS.

Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults.

PURPOSE: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study. METHODS AND MATERIALS: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004. Radiologists or surgeons assessed disease characteristics, such as volume and extension. Patients were classified as having either high- or standard-risk disease. Prognostic factors were analyzed. RESULTS: Median patient age was 29 years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5- and 10-year overall survival rates were 72% and 55%. Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF). By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors. In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of >or=34 Gy and patients treated with craniospinal doses <34 Gy plus chemotherapy. CONCLUSION: We report the largest series of medulloblastoma in adults. Prognostic factors were similar to those observed in children. Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF. The role of chemotherapy for this group is still unclear. A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult.

[For a coordination of the supportive care for people affected by severe illnesses: proposition of organization in the public and private health care centres]. / Coordination des soins de support pour les personnes atteintes de maladies graves: proposition d'organisation dans les etablissements de soins publics et privés.

The concept of continuous and global care is acknowledged today by all as inherent to modern medicine. A working group gathered to propose models for the coordination of supportive care for all severe illnesses in the various private and public health care centres. The supportive care are defined as: "all care and supports necessary for ill people, at the same time as specific treatments, along all severe illnesses". This definition is inspired by that of "supportive care" given in 1990 by the MASCC (Multinational Association for Supportive Care in Cancer): "The total medical, nursing and psychosocial help which the patients need besides the specific treatment". It integrates as much the field of cure with possible after-effects as that of palliative care, the definition of which is clarified (initial and terminal palliative phases). Such a coordination is justified by the pluridisciplinarity and hyperspecialisation of the professionals, by a poor communication between the teams, by the administrative difficulties encountered by the teams participating in the supportive care. The working group insists on the fact that the supportive care is not a new speciality. He proposes the creation of units. departments or pole of responsibility of supportive care with a "basic coordination" involving the activities of chronic pain, palliative care, psycho-oncology, and social care. This coordination can be extended, according to the "history" and missions of health care centres. Service done with the implementation of a "unique counter" for the patients and the teams is an important point. The structure has to comply with the terms and conditions of contract (Consultation, Unit or Centre of chronic pain, structures of palliative care, of psycho-oncology, of nutrition, of social care). A common technical organization is one of the interests. The structure has to set up strong links with the private practitioners, the networks, the home medical care (HAD) and the nurses services at home (SSIAD), when they exist, to guarantee the continuity of the supportive care under all its aspects and in order to take into account the preferences of the patients. According to Hospital 2007 propositions, the extended, flexible and general purpose Group of Sanitary Cooperation (GCS) meets the necessities inherent to the structures of supportive care within the territories of health because it can be established between one or several health care centres and the private health professionals, thus favouring the cooperation between public and private health care centres. PSPH and general medicine.

[Standards, options and recommendations for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer (update 2002): opioid analgesics with the exception of morphine by mouth and the rotation]. / Standards, Options et Recommandations 2002 pour les traitements antalgiques médicamenteux des douleurs cancéreuses par excès de nociception chez l'adulte, mise à jour : place des opioïdes forts (morphine orale exclue) et rotation des opioïdes.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the federation of French Cancer Centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the use of opioid analgesics with the exception of oral morphine and for opioid rotation related to the treatment of nociceptive pain in adults with cancer according to the definitions of the Standards, Options and Recommendations project. METHODS: In 1996, a working group, set up by the FNCLCC published clinical practice guidelines for pain management in adult and paediatric patients with cancer: In the light of the evolution of knowledge, and practice these guidelines need to be updated The section on "médical analgesic treatments" in the document published in 1996 was examined by the working group to identify which questions should be updated. These questions and the relevant key words were used to develop a search strategy which was used to search Medline, and for particular questions, Embase, from January 1994 to March 1999, for relevant references, published in English or French. RESULTS: For this update, only a few randomised clinical trials were identified, and their conclusions were generally weak. Thus much of the information in this document is based on the World Health Organisation (WHO) guidelines and represents the "state of the art" on this subject in France and is supported by expert agreement. Some changes to the original SOR are presented, particularly for the prescription of new opioids and opioid rotation. The full text of this SOR is available on the FNCLCC web site (http ://www.fnclcc.fr).

A phase II study of docetaxel-irinotecan combination in advanced pancreatic cancer.

BACKGROUND/AIMS: Chemotherapy provides dismal results in advanced pancreatic cancer patients, even when new compounds, such as gemcitabine, are used. Phase I studies of single-drug therapy with docetaxel or irinotecan suggested a response rate of about 15% in these patients. We report here a phase II study of docetaxel-irinotecan combination in advanced pancreatic cancer patients. METHODOLOGY: Docetaxel 60 mg/m2 was given in combination with irinotecan 250 mg/m2 every 3 weeks. Prednisolone premedication and anti-HT3 drugs were systematically administered. Hematopoietic growth factors were given in case of febrile neutropenia or grade 4 neutropenia at the previous cycle. Endpoints were response rate, progression-free survival, and tolerance. RESULTS: Twenty-seven patients were enrolled, of whom 25 had metastatic disease. We observed 3 partial responses and 11 stabilizations. The median progression-free survival was 4.3 months. Myelosuppression was the main toxicity with 18% of patients experiencing a grade 3-4 event. One patient died of neglected febrile neutropenia. Gastrointestinal toxicity was well controlled. Other toxicities were mild. CONCLUSIONS: This combination has acceptable tolerance and, despite an 11% response rate, some partial responses and prolonged stabilizations were observed. The treatment induced clinical benefit in 33% of the patients. Further trials should focus on docetaxel or irinotecan, possibly used in combination with more conventional strategies (gemcitabine).

Clinical predictors of exercise capacity 1 year after cardiac transplantation.

BACKGROUND: The exercise capacity of cardiac transplant recipients is reduced compared with normal controls. However, clinical variables predictive of post-transplant exercise capacity have not been well defined. The objective of the present study was to identify clinical features predictive of post-transplant exercise capacity. METHODS: Ninety-five cardiac transplant recipients underwent cardiopulmonary testing at 1 year after transplant. The exercise parameters were compared with both pre-transplant values and normal subjects. The relationships between exercise parameters and clinical characteristics were analyzed. RESULTS: Mean peak oxygen consumption (VO(2)) and exercise test duration at 1-year post-transplant improved significantly from 16.4 to 19.9 ml/kg/min and 5.5 to 7.6 minutes, respectively (p < 0.001), but were significantly lower than for normal controls (peak VO(2) 34.0 ml/kg/min; exercise duration 11.2 minutes; p < 0.001). Age- and gender-adjusted VO(2) was 54% of predicted. Pre-operative body weight correlated strongly with post-transplant weight (r = 0.80, p < 0.001). Significant recipient predictors of 1-year post-transplant peak VO(2) identified by multivariate regression analysis were age, male gender, body mass index, exercise peak heart rate and duration of post-operative intensive care. Donor variables did not contribute significantly to post-transplant peak VO(2). CONCLUSIONS: Peak VO(2) improved after cardiac transplantation but remained significantly impaired compared with normal subjects. In estimating the impact of cardiac transplantation on exercise capacity the most important pre-transplant factors to consider are age, gender and height and weight (or, alternatively, body mass index).

Partial normalization of the heart rate response to exercise after cardiac transplantation: frequency and relationship to exercise capacity.

OBJECTIVE: To determine the frequency of partial normalization of the heart rate response to graded exercise and its relationship to exercise capacity in cardiac transplant recipients. SUBJECTS AND METHODS: The study subjects were 95 adults (77 men, 18 women) who were available to perform a cardiopulmonary exercise test 1 year after orthotopic cardiac transplantation, which occurred between June 1988 and September 1998. All subjects received standard immunosuppressant medications. At the time of the exercise tests, the mean +/- SD age of the subjects was 49+/-14 years. The mean +/- SD resting left ventricular ejection fraction was 62%+/-8%. All subjects participated in a 6- to 8-week supervised exercise program, starting no later than 1 month after surgery. Subjects were given an exercise prescription for independent exercise training after finishing the supervised program. Self-reported weekly exercise training had a median value of 90 minutes (interquartile range, 0-210 minutes). Symptom-limited graded exercise was performed on a treadmill, with breath-by-breath analysis of expired air. RESULTS: For the entire cohort, peak exercise oxygen uptake was 19.9+/-4.8 mL x kg(-1) x min(-1) (61%+/-15% of age and sex predicted). Thirty-two subjects (34%) had a partially normalized heart rate response to graded exercise. The frequency was similar for men (25/77 [33%]) and for women (7/18 [39%]) and was independent of recipient or donor age. Peak exercise heart rate (147+/-18 vs 134+/-21 beats/min; P=.008) and heart rate reserve (46+/-15 vs 33+/-15 beats/min; P<.001) were greater for subjects with a partial normalization of heart rate response. Peak exercise oxygen uptake was similar for subjects with or without partial normalization of the heart rate response (20.9+/-5.8 vs 19.4+/-4.2 mL x kg(-1) x min(-1); P=.22). Submaximal exercise oxygen uptake during the first few minutes of exercise was also not affected by normalization of the heart rate response. CONCLUSION: At 1 year after cardiac transplantation, approximately one third of subjects had partial normalization of the heart rate response to graded exercise. However, a higher peak exercise heart rate and a larger heart rate reserve did not result in better aerobic exercise capacity.