Publications by authors named "Monica Escher"

29 Publications

  • Page 1 of 1

Physicians' Views and Agreement about Patient- and Context-Related Factors Influencing ICU Admission Decisions: A Prospective Study.

J Clin Med 2021 Jul 11;10(14). Epub 2021 Jul 11.

Division of Palliative Medicine, Department of Readaptation and Geriatrics, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva, Switzerland.

Background: Single patient- and context-related factors have been associated with admission decisions to intensive care. How physicians weigh various factors and integrate them into the decision-making process is not well known.

Objectives: First, to determine which patient- and context-related factors influence admission decisions according to physicians, and their agreement about these determinants; and second, to examine whether there are differences for patients with and without advanced disease.

Method: This study was conducted in one tertiary hospital. Consecutive ICU consultations for medical inpatients were prospectively included. Involved physicians, i.e., internists and intensivists, rated the importance of 13 factors for each decision on a Likert scale (1 = negligible to 5 = predominant). We cross-tabulated these factors by presence or absence of advanced disease and examined the degree of agreement between internists and intensivists using the kappa statistic.

Results: Of 201 evaluated patients, 105 (52.2%) had an advanced disease, and 140 (69.7%) were admitted to intensive care. The mean number of important factors per decision was 3.5 (SD 2.4) for intensivists and 4.4 (SD 2.1) for internists. Patient's comorbidities, quality of life, preferences, and code status were most often mentioned. Inter-rater agreement was low for the whole population and after stratifying for patients with and without advanced disease. Kappa values ranged from 0.02 to 0.34 for all the patients, from -0.05 to 0.42 for patients with advanced disease, and from -0.08 to 0.32 for patients without advanced disease. The best agreement was found for family preferences.

Conclusion: Poor agreement between physicians about patient- and context-related determinants of ICU admission suggests a lack of explicitness during the decision-making process. The potential consequences are increased variability and inequity regarding which patients are admitted. Timely advance care planning involving families could help physicians make the decision most concordant with patient preferences.
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http://dx.doi.org/10.3390/jcm10143068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305175PMC
July 2021

Physicians' perspective on potentially non-beneficial treatment when assessing patients with advanced disease for ICU admission: a qualitative study.

BMJ Open 2021 05 21;11(5):e046268. Epub 2021 May 21.

Department of Primary Care, University Hospitals of Geneva, Geneva, Switzerland.

Objective: The use of intensive care at the end of life can be high, leading to inappropriate healthcare utilisation, and prolonged suffering for patients and families. The objective of the study was to determine which factors influence physicians' admission decisions in situations of potentially non-beneficial intensive care.

Design: This is a secondary analysis of a qualitative study exploring the triage process. In-depth interviews were analysed using an inductive approach to thematic content analysis.

Setting: Data were collected in a Swiss tertiary care centre between March and June 2013.

Participants: 12 intensive care unit (ICU) physicians and 12 internists routinely involved in ICU admission decisions.

Results: Physicians struggled to understand the request for intensive care for patients with advanced disease and full code status. Physicians considered patients' long-term vital and functional prognosis, but they also resorted to shortcuts, that is, a priori consensus about reasons for admitting a patient. Family pressure and unexpected critical events were determinants of admission to the ICU. Patient preferences, ICU physician's expertise and collaborative decision making facilitated refusal. Physicians were willing to admit a patient with advanced disease for a limited amount of time to fulfil a personal need.

Conclusions: In situations of potentially non-beneficial intensive care, the influence of shortcuts or context-related factors suggests that practice variations and inappropriate admission decisions are likely to occur. Institutional guidelines and timely goals of care discussions with patients with advanced disease and their families could contribute to ensuring appropriate levels of care.
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http://dx.doi.org/10.1136/bmjopen-2020-046268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144032PMC
May 2021

Early advance care planning in amyotrophic lateral sclerosis patients: results of a systematic intervention by a palliative care team in a multidisciplinary management programme - a 4-year cohort study.

Swiss Med Wkly 2021 Mar 18;151:w20484. Epub 2021 Mar 18.

Palliative Care Consultation, Division of Palliative Medicine, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Switzerland / Unit for Development and Research in Medical Education (UDREM), Faculty of Medicine, University of Geneva, Switzerland.

Introduction: Although recommended, the implementation of early advance care planning is suboptimal in amyotrophic lateral sclerosis (ALS) patients. Barriers to advance care planning include healthcare professionals’ and patients’ reluctance, and uncertainty about the right time to initiate a discussion.

Aim Of The Study: To determine how often advance care planning was initiated, and the content of the discussion in a first routine palliative care consultation integrated within a multidisciplinary management programme.

Methods: Between June 2012 and September 2016, a prospective cohort study was conducted in Geneva University Hospitals. Sixty-eight patients were seen every 3 months for a 1-day clinical evaluation in a day care centre.

Results: The patients’ mean ± standard deviation age was 68.6 ± 11.9 years, 50% were women. Four patients were excluded because of dementia. Advance care planning was initiated with 49 (77%) patients in the first palliative care consultation. Interventions most often addressed were cardiopulmonary resuscitation (49%), intubation and tracheostomy (47%) and palliative sedation (36.7%). Assisted suicide was discussed with 16 patients (36.6%). Functional disability was the only factor associated with initiation of advance care planning. Nearly half of the patients wrote advance directives (45%) or designated a healthcare surrogate (41%). Bulbar onset, functional disability and noninvasive ventilation were not associated with the completion of advance directives.

Conclusion: Early initiation of advance care planning is feasible in most ALS patients during a routine consultation, and relevant treatment issues can be discussed. All ALS patients should be offered the opportunity to write advance directives as completion was not associated with disease severity. .
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http://dx.doi.org/10.4414/smw.2021.20484DOI Listing
March 2021

Physicians' predictions of long-term survival and functional outcomes do not influence the decision to admit patients with advanced disease to intensive care: A prospective study.

Palliat Med 2021 01 16;35(1):161-168. Epub 2020 Oct 16.

Division of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland.

Background: Long-term survival and functional outcomes should influence admission decisions to intensive care, especially for patients with advanced disease.

Aim: To determine whether physicians' predictions of long-term prognosis influenced admission decisions for patients with and without advanced disease.

Design: A prospective study was conducted. Physicians estimated patient survival with intensive care and with care on the ward, and the probability of 4 long-term outcomes: leaving hospital alive, survival at 6 months, recovery of functional status, and recovery of cognitive status. Patient mortality at 28 days was recorded. We built multivariate logistic regression models using admission to the intensive care unit (ICU) as the dependent variable.

Setting/participants: ICU consultations for medical inpatients at a Swiss tertiary care hospital were included.

Results: Of 201 evaluated patients, 105 (52.2%) had an advanced disease and 140 (69.7%) were admitted to the ICU. The probability of admission was strongly associated with the expected short-term survival benefit for patients with or without advanced disease. In contrast, the predicted likelihood that the patient would leave the hospital alive, would be alive 6 months later, would recover functional status, and would recover initial cognitive capacity was not associated with the decision to admit a patient to the ICU. Even for patients with advanced disease, none of these estimated outcomes influenced the admission decision.

Conclusions: ICU admissions of patients with advanced disease were determined by short-term survival benefit, and not by long-term prognosis. Advance care planning and developing decision-aid tools for triage could help limit potentially inappropriate admissions to intensive care.
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http://dx.doi.org/10.1177/0269216320963931DOI Listing
January 2021

Multidisciplinary care in amyotrophic lateral sclerosis: a 4-year longitudinal observational study.

Swiss Med Wkly 2020 Jun 9;150:w20258. Epub 2020 Jun 9.

Division of Pulmonary Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland / Faculty of Medicine, University of Geneva, Switzerland.

Over a four-year period, ALS patients complied with the modalities of the multidisciplinary management follow-up without any drop-outs. The multidisciplinary management structure also contributes to increasing the experience and knowledge of the clinicians involved in managing patients suffering from this rare disease.
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http://dx.doi.org/10.4414/smw.2020.20258DOI Listing
June 2020

Comparison of long-menu and single-best-answer multiple choice questions in computer-based summative assessments: a randomised controlled trial.

BMC Med Educ 2019 Jun 18;19(1):219. Epub 2019 Jun 18.

Department of Paediatrics, Children's Hospital, University Hospitals of Geneva, Geneva, Switzerland.

Background: Little is known regarding the psychometric properties of computerized long-menu formats in comparison to classic formats. We compared single-best-answer (Type A) and long-menu formats using identical question stems during the computer-based, summative, intermediate clinical-clerkship exams for nine disciplines.

Methods: In this randomised sequential trial, we assigned the examinees for every summative exam to either the Type A or long-menu format (four different experimental questions, otherwise identical). The primary outcome was the power of discrimination. The study was carried out at the Faculty of Medicine, University of Geneva, Switzerland, and included all the students enrolled for the exams that were part of the study. Examinees were surveyed about the long-menu format at the end of the trial.

Results: The trial was stopped for futility (p = 0.7948) after 22 exams including 88 experimental items. The long-menu format had a similar discriminatory power but was more difficult than the Type A format (71.45% vs 77.80%; p = 0.0001). Over half of the options (54.4%) chosen by the examinees in long-menu formats were not proposed as distractors in the Type A formats. Most examinees agreed that their reasoning strategy was different.

Conclusions: In a non-selected population of examinees taking summative exams, long-menu questions have the same discriminatory power as classic Type A questions, but they are slightly more difficult. They are perceived to be closer to real practice, which could have a positive educational impact. We would recommend their use in the final years of the curriculum, within realistic key-feature problems, to assess clinical reasoning and patient management skills.
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http://dx.doi.org/10.1186/s12909-019-1651-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582573PMC
June 2019

ICU physicians' and internists' survival predictions for patients evaluated for admission to the intensive care unit.

Ann Intensive Care 2018 Nov 14;8(1):108. Epub 2018 Nov 14.

Division of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland.

Background: A higher chance of survival is a key justification for admission to the intensive care unit (ICU). This implies that physicians should be able to accurately estimate a patient's prognosis, whether cared for on the ward or in the ICU. We aimed to determine whether physicians' survival predictions correlate with the admission decisions and with patients' observed survival. Consecutive ICU consultations for internal medicine patients were included. The ICU physician and the internist were asked to predict patient survival with intensive care and with care on the ward using 5 categories of probabilities (< 10%, 10-40%, 41-60%, 61-90%, > 90%). Patient mortality at 28 days was recorded.

Results: Thirty ICU physicians and 97 internists assessed 201 patients for intensive care. Among the patients, 140 (69.7%) were admitted to the ICU. Fifty-eight (28.9%) died within 28 days. Admission to intensive care was associated with predicted survival gain in the ICU, particularly for survival estimates made by ICU physicians. Observed survival was associated with predicted survival, for both groups of physicians. The discrimination of the predictions for survival with intensive care, measured by the area under the ROC curve, was 0.63 for ICU physicians and 0.76 for internists; for survival on the ward the areas under the ROC curves were 0.69 and 0.74, respectively.

Conclusions: Physicians are able to predict survival probabilities when they assess patients for intensive care, albeit imperfectly. Internists are more accurate than ICU physicians. However, ICU physicians' estimates more strongly influence the admission decision. Closer collaboration between ICU physicians and internists is needed.
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http://dx.doi.org/10.1186/s13613-018-0456-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236006PMC
November 2018

Admission to intensive care: A qualitative study of triage and its determinants.

Health Serv Res 2019 04 25;54(2):474-483. Epub 2018 Oct 25.

Pain and Palliative Care Consultation, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.

Objective: To examine physicians' decision making and its determinants about admission to intensive care.

Data Sources/study Setting: ICU physicians (n = 12) and internists (n = 12) working in a Swiss tertiary care hospital.

Study Design: We conducted in-depth interviews.

Data Collection/extraction Methods: Interviews were analyzed using an inductive thematic approach.

Principal Findings: Admission decisions regarding seriously ill or elderly patients with comorbidities are complex. Nonmedical factors such as ICU beds availability, health care resources on the ward, information about patient preferences, and family behavior determine the decision. Code status and the quality of interaction between physicians are key determinants. The absence of code status or poor documentation of code status discussions makes decisions more difficult and laden emotionally, as physicians feel they are making a life-death decision. Mutual respect and collaborative decision making facilitate the decision. Tensions arise due to ICU physicians' postponing the decision because of lack of beds, ICU physicians' dismissive attitudes, perceived shortcomings in the other physician's completion of expected tasks, and preconceptions about the other physician.

Conclusions: Systematic documentation of code status, and fostering collaboration between ICU physicians and internists would facilitate ICU admission decisions in complex clinical situations.
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http://dx.doi.org/10.1111/1475-6773.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407353PMC
April 2019

[Would you want to be resuscitated if you heart stops Code status discussions in the hospital setting].

Rev Med Suisse 2018 Oct;14(623):1854-1858

Equipe mobile douleur et soins palliatifs, Service de pharmacologie et toxicologie cliniques, Département d'anesthésiologie, pharmacologie et soins intensifs, HUG, 1211 Genève 14.

Doctors are responsible for code status discussions with patients in the hospital setting. However, several barriers are associated with these discussions, relating to both doctors and patients. Inadequate or insufficient communication can lead to inappropriate care, contrary to patients' preferences and, subsequently, to a suboptimal use of health care resources. Ways to improve these discussions have been identified, such as doctor-targeted educational programs and inserting decisions about code status within a more general discussion of patients' goals of care. These interventions could allow a better understanding and consideration of patients' values and preferences, hence improving shared-decision making about cardiopulmonary resuscitation.
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October 2018

Internists' and intensivists' roles in intensive care admission decisions: a qualitative study.

BMC Health Serv Res 2018 08 8;18(1):620. Epub 2018 Aug 8.

Pain and Palliative Care Consultation, Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland.

Background: Intensive care Unit (ICU) admission decisions involve collaboration between internists and intensivists. Clear perception of each other's roles is a prerequisite for good collaboration. The objective was to explore how internists and intensivists perceive their roles during admission decisions.

Methods: Individual in-depth interviews with 12 intensivists and 12 internists working at a Swiss teaching hospital. Interviews were analyzed using a thematic approach.

Results: Roles could be divided into practical roles and identity roles. Internist and intensivists had the same perception of each other's practical roles. Internists' practical roles were: recognizing signs of severity when the patient becomes acutely ill, calling the intensivist at the right moment, having the relevant information about the patient and having determined the goals of care. Intensivists' practical roles were: assessing the patient on the ward, giving expert advice, making quick decisions, managing access to the ICU, having the final decision power and, sometimes, deciding whether or not to limit treatment. In complex situations, perceived flaws in performing practical roles could create tensions between the doctors. Intensivists' identity roles included those of leader, gatekeeper, life-death decision maker, and supporting colleague doctors (consultant, senior and helper). These roles could be perceived as emotionally burdensome. Internists' identity roles were those of leader and partner.

Conclusions: Despite a common perception of each other's practical roles, tensions can arise between internists and intensivists in complex situations of ICU admission decisions. Training in communication skills and interprofessional education interventions aimed at a better understanding of each other roles would improve collaboration.
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http://dx.doi.org/10.1186/s12913-018-3438-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083517PMC
August 2018

[Pain management in adult medico-surgical wards : practical guidelines].

Rev Med Suisse 2018 Jun;14(612):1296-1300

Service de pharmacologie et toxicologie cliniques, HUG, 1211 Genève 14.

Guidelines for pain management in the medical and surgical departments of the Geneva University Hospitals (GUH) have been systematically developed using a multidisciplinary approach. These guidelines are aimed towards improving healthcare quality. We point to the ways the pain network of the GUH has elected to deal with the ever-increasing progression of concepts regarding pain management. This is of importance at a time when the risks related to the patients' transitions between the different departments, to the specificities of the clinical practices, and to the need for personalized care have never been so high.
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June 2018

Feelings of Burden in Palliative Care: A Qualitative Analysis of Medical Records.

J Palliat Care 2018 Jan 4;33(1):32-38. Epub 2018 Jan 4.

1 Institute for Biomedical Ethics, University of Basel, Basel, Switzerland.

Background: Care for palliative care patients is often provided by unpaid caregivers (eg, family members) who take care of the patient's daily needs (eg, bathing, dressing). Family members of palliative care patients are involved in numerous ways. These tasks and responsibilities can make them feel burdened and even overburdened.

Aim: We specifically looked at patients' medical records to determine what is being reported about burden and overburden and who seems to be mostly affected. Burden was understood as a weight or task that is difficult to accept or carry, whereas overburden indicates that this weight or task cannot be carried anymore.

Methods: We looked at 300 medical records of palliative care patients written by health-care professionals. Written notes were analyzed using latent content analysis as it helps to analyze large amounts of textual data qualitatively and to understand the underlying concepts of what was said.

Results: Most (73.5%) patients had a cancer diagnosis. Mean age was 67.6 years (range, 22-98 years). Burden and overburden were identified as main categories and further divided into the following subcategories: for patients and families. According to the written notes, patients often felt burdened by their disease, financial problems, situation at home, and families' reactions to their disease. By and large, patients felt overburdened by their own disease. Families often felt burdened because of issues related to patients' medical condition, providing home care, or financial and social aspects. Families mentioned home care and the decision-making process as being overburdening.

Conclusion: Findings in the palliative care patients' medical records are inasmuch important, as they point at the health-care staff's awareness of possible weights and tasks that might be burdensome for patients and their families. Attention should be drawn to the documentation of medical records in order to identify recurrent difficulties and to help discuss these.
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http://dx.doi.org/10.1177/0825859717750522DOI Listing
January 2018

Validation of the French Version of the Edmonton Symptom Assessment System.

J Pain Symptom Manage 2017 11 25;54(5):721-726.e1. Epub 2017 Jul 25.

Pain and Palliative Care Consultation, Division of Pharmacology and Toxicology, University Hospital Geneva and Geneva University, Geneva, Switzerland.

Context: The Edmonton Symptom Assessment System (ESAS) is a brief, widely adopted, multidimensional questionnaire to evaluate patient-reported symptoms.

Objectives: The objective of this study was to define a standard French version of the ESAS (F-ESAS) to determine the psychometric properties in French-speaking patients.

Methods: In a first pilot study, health professionals (n = 20) and patients (n = 33) defined the most adapted terms in French (F-ESAS). In a prospective multicentric study, palliative care patients completed the three forms of F-ESAS (F-ESAS-VI, F-ESAS-VE, and F-ESAS-NU, where VI is visual, VE, verbal, and NU, numerical), the Hospital Anxiety and Depression Scale. All patients had a test-retest evaluation during the same half-day. Standardized distraction material was used between each scale.

Results: One hundred twenty-four patients were included (mean age [±SD]: 68.3 ± 12; 70 women; 54 men). Test-retest reliability was high for all three F-ESAS, and the correlation between these scales was nearly perfect (Spearman rs = 0.66-0.91; P < 0.05). F-ESAS-VI, F-ESAS-VE, and F-ESAS-NU performed similarly and were equally reliable, although there was a trend toward lower reliability for F-ESAS-VI. Correlation between F-ESAS depression and anxiety and HADS depression and anxiety, respectively, were positive (Spearman rs = 0.38-0.41 for depression; Spearman rs = 0.48-0.57 for anxiety, P < 0.05). Among patients, 59 (48%), 45 (36%), and 20 (16%) preferred to assess their symptoms with F-ESAS-VE, F-ESAS-NU, and F-ESAS-VI, respectively.

Conclusion: The F-ESAS is a valid and reliable tool for measuring multidimensional symptoms in French-speaking patients with an advanced cancer. All forms of F-ESAS performed well with a trend for better psychometric performance for F-ESAS-NU, but patients preferred the F-ESAS-VE.
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http://dx.doi.org/10.1016/j.jpainsymman.2017.07.032DOI Listing
November 2017

[Admission to intensive care of palliative care patients : the stakes and factors influencing the decision].

Rev Med Suisse 2017 Feb;13(548):323-325

Service des soins intensifs, HUG, 1211 Genève 14.

Palliative care patients have limited prospects of survival and the benefit of intensive care is uncertain. To make a decision there are considerations other than survival probabilities. Patients should receive appropriate care and be spared suffering. End of life in the intensive care unit has an impact on families, who may develop psychological problems or complicated grief. End of life care can be a source of conflicts and cause burnout in health providers. Finally, intensive care is an expensive resource, which must be fairly allocated. In these complex situations, patient preferences help make a decision. However, they have often not been discussed with the physicians. General practitioners have a role to play by promoting advance care planning with their patients.
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February 2017

Should gratitude be a requirement for access to live organ donation?

J Med Ethics 2017 11 29;43(11):762-765. Epub 2017 Mar 29.

Clinical Ethics Council, Geneva University Hospitals, Geneva, Switzerland.

Gratitude is both expected and problematic in live organ donation. Are there grounds to require it, and to forbid access to live donor transplantation to a recipient who fails to signal that he feels any form of gratitude? Recipient gratitude is not currently required for organ donation, but it is expected and may be a moral requirement. Despite this, we argue that making it a condition for live organ transplantation would be unjustified. It would constitute a problematic and disproportionate punishment for perceived immoral behaviour on the part of the recipient. It would also bar the donor from positive aspects of organ donation that remain even in the absence of recipient gratitude. A potential recipient's lack of gratitude should be explored as a possible symptom of other morally problematic issues and integrated into the information provided to the potential donor. Recognition of the donor's gift and gratitude for it may also need to be expressed in part by others. This last aspect is relevant even in cases where the recipient feels and expresses gratitude.
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http://dx.doi.org/10.1136/medethics-2016-103698DOI Listing
November 2017

Preventive Treatments for Rheumatoid Arthritis: Issues Regarding Patient Preferences.

Curr Rheumatol Rep 2016 08;18(8):51

School of Population and Public Health, University of British Columbia, Vancouver, Canada.

The detection of biomarkers in the preclinical phase of rheumatoid arthritis (RA) and recent therapeutic advances suggest that it may be possible to identify and treat persons at high risk and to prevent the development of RA. Several trials are ongoing to test the efficacy of a therapeutic intervention in primary prevention. This paper reviews potential populations that might be considered for preventative medication. Further, we review the medications that are being explored to treat individuals considered at high risk of developing RA. Finally, in a group of asymptomatic individuals at high risk of developing RA, we assessed which factors mattered most when considering a preventive therapeutic intervention and what type of preventive treatment would be most acceptable to them. Understanding subjects' perceptions of risks and benefits and willingness to undergo preventive therapy will be important in designing and implementing screening and preventive strategies.
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http://dx.doi.org/10.1007/s11926-016-0598-4DOI Listing
August 2016

Severe liver injury due to a homemade flower pollen preparation in a patient with high CYP3A enzyme activity: a case report.

Eur J Clin Pharmacol 2016 Apr 8;72(4):507-8. Epub 2016 Jan 8.

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, CH-1211, Geneva, Switzerland.

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http://dx.doi.org/10.1007/s00228-015-1986-9DOI Listing
April 2016

Severe Vincristine-induced Neuropathic Pain in a CYP3A5 Nonexpressor With Reduced CYP3A4/5 Activity: Case Study.

Clin Ther 2016 Jan 10;38(1):216-20. Epub 2015 Nov 10.

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland. Electronic address:

Purpose: Peripheral neuropathy is a frequent vincristine-induced adverse effect. Vincristine is a substrate of P-glycoprotein and is metabolized by the cytochrome P-450 (CYP) 3A5 and 3A4 isoforms, with CYP3A5 contributing to 75% of the intrinsic clearance of vincristine. Alterations in the function of these proteins may lead to an increase in vincristine toxicity. CYP3A5 nonexpressor status has been associated with vincristine-induced peripheral neuropathy. The severity of neuropathy has been reported to be inversely correlated to vincristine metabolite concentrations. Recently, the presence of a mutation in the CEP72 gene, which encodes for a protein involved in microtubule formation, has also been associated with vincristine-induced peripheral neuropathy. However, a clear correlation between genetic polymorphisms and vincristine toxicity has not been established.

Methods: Here we report the case of a 21-year old patient in whom severe neuropathic pain developed after vincristine treatment.

Findings: The patient was a CYP3A5 nonexpressor and presented with reduced CYP3A4/5 functional activity, a likely reason for the occurrence of the adverse event, as genotyping showed that his status was wild type for the ABCB1 and CEP72 genes.

Implications: CYP phenotype and genotype may explain the occurrence of severe neuropathy in some patients treated with vincristine.
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http://dx.doi.org/10.1016/j.clinthera.2015.10.017DOI Listing
January 2016

Doctors' decisions when faced with contradictory patient advance directives and health care proxy opinion: a randomized vignette-based study.

J Pain Symptom Manage 2015 Mar 15;49(3):637-45. Epub 2014 Aug 15.

Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.

Context: Sometimes a written advance directive contradicts the opinion of a health care proxy. How this affects doctors' decision making is unknown.

Objectives: To quantify the influence of contradictory instructions on doctors' decisions.

Methods: All the generalists and internists in French-speaking Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three vignettes that described medical decisions for incapacitated patients. Each vignette was produced in four versions: one with an advance directive, one with a proxy opinion, one with both, and one with neither (control). In the first vignette, the directive and proxy agreed on the recommendation to forgo a medical intervention; in the second, the advance directive opposed, but the proxy favored the intervention; and in the third, the roles were reversed. Each doctor received one version of each vignette, attributed at random. The outcome variables were the doctor's decision to forgo the medical intervention and the rating of the decision as difficult.

Results: Written advance directives and proxy opinions significantly influenced doctors' decision making. When both were available and concordant, they reinforced each other (odds ratio [OR] of forgoing intervention 35.7, P < 0.001 compared with no instruction). When the directive and proxy disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2 for the two discordant vignettes, both P < 0.001). Discordance between instructions was associated with increased odds of doctors rating the decision as difficult (both ORs 2.0, P ≤ 0.001).

Conclusion: Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision.
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http://dx.doi.org/10.1016/j.jpainsymman.2014.06.012DOI Listing
March 2015

Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity.

AIDS Res Ther 2014 4;11:25. Epub 2014 Aug 4.

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.

Background: Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.

Case Presentation: A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range.

Conclusion: The integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.
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http://dx.doi.org/10.1186/1742-6405-11-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130425PMC
August 2014

Volunteers trained in palliative care at the hospital: an original and dynamic resource.

Palliat Support Care 2015 Jun 24;13(3):601-7. Epub 2014 Apr 24.

Division of Clinical Pharmacology and Toxicology,Consultation for Pain and Palliative Care Center,University Hospitals of Geneva Faculty of Medicine,Geneva,Switzerland.

Objective: Volunteers trained in palliative care are increasingly present in acute care units in general hospitals. Nevertheless, there still are few available data on this topic, especially concerning the integration of volunteers outside the palliative structures. Our present study aimed to describe the experience of volunteers trained in palliative care in the context of a primary care hospital. In particular, the difficulties and the benefits of this specific position were evaluated according to volunteers' own perceptions and words.

Method: We employed a qualitative method. Various aspects of the volunteer's role were explored by means of semistructured questions, addressing their activity, their motivations, and their feelings. Participants were volunteers (n = 19) trained in palliative care and working at a university hospital. After giving written consent, they completed the semistructured questionnaire at home. Content analysis was used to identify the main categories of answers and the principal themes reported by the volunteers.

Results: The main difficulties were related to uncertainty of the context. As every situation is different, volunteers could not define their role once and for all. However, they derived great satisfaction from their activity. A supporting frame and a good balance between constraints and autonomy were facilitating factors. Besides, the complexity related to the context contributed to make the position valuable and challenging.

Significance Of Results: Integrating a voluntary service in a primary care hospital is partly based on active participation of the volunteers in developing their position in a more adequate way. In return, this relative autonomy implies a rigorous and supportive attitude from the institution.
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http://dx.doi.org/10.1017/S1478951514000169DOI Listing
June 2015

Is tracheostomy still an option in amyotrophic lateral sclerosis? Reflections of a multidisciplinary work group.

Swiss Med Wkly 2013 7;143:w13830. Epub 2013 Aug 7.

Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals, Switzerland.

Question Under Study: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis. Survival and quality of life of ALS patients have improved through the implementation of multidisciplinary approaches, the use of percutaneous gastrostomy and of noninvasive (NIV) or invasive ventilation. The question of whether or not to propose invasive ventilation (by tracheostomy: TPPV) to ALS patients remains a matter of debate.

Methods: The study reviews the medical literature, the practice in three Swiss and two large French ALS expert centres and reports the results of a workgroup on invasive ventilation in ALS.

Results: Improved management of secretions and use of different interfaces allows NIV to be used 24-hours-a-day for prolonged periods, thus avoiding TPPV in many cases. TPPV is frequently initiated in emergency situations with lack of prior informed consent. TPPV appears associated with a lesser quality of life and a higher risk of institutionalisation than NIV. The high burden placed on caregivers who manage ALS patients is a major problem with a clear impact on their quality of life.

Conclusions: Current practice in Switzerland and France tends to discourage the use of TPPV in ALS. Fear of a "locked-in syndrome", the high burden placed on caregivers, and unmasking cognitive disorders occurring in the evolution of ALS are some of the caveats when considering TPPV. Most decisions about TPPV are taken in emergency situations in the absence of advance directives. One exception is that of young motivated patients with predominantly bulbar disease who "fail" NIV.
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http://dx.doi.org/10.4414/smw.2013.13830DOI Listing
December 2013

Primary prevention of rheumatoid arthritis: a qualitative study in a high-risk population.

Joint Bone Spine 2013 Dec 5;80(6):673-4. Epub 2013 Jul 5.

Université de Genève, Geneva, Switzerland.

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http://dx.doi.org/10.1016/j.jbspin.2013.05.005DOI Listing
December 2013

Impact of advance directives and a health care proxy on doctors' decisions: a randomized trial.

J Pain Symptom Manage 2014 Jan 4;47(1):1-11. Epub 2013 Jun 4.

Division of General Internal Medicine, University Hospitals of Geneva, Geneva, Switzerland.

Context: Advance directives or proxy designations are widely recommended, but how they affect doctors' decision making is not well known.

Objectives: The aim of this study was to quantify the influence of advance directives and proxy opinions on doctors' decisions.

Methods: We mailed to all the generalists and internists in French-speaking Switzerland (N = 1962) three vignettes describing difficult decisions involving incapacitated patients. In each case, the advance directive requested that further care be withheld. One vignette tested the impact of a written advance directive vs. a proxy. Another compared the impact of a handwritten directive vs. a formalized document. The third vignette compared the impact of a family member vs. a doctor as a proxy. Each vignette was prepared in three or four versions, including a control version in which no directive or proxy was present. Vignettes were randomly allocated to respondents. We used logistic regression to predict the decision to forgo a medical intervention.

Results: Compared with the control condition, the odds of forgoing a medical intervention were increased by the written advance directive (odds ratio [OR] 7.3; P < 0.001), the proxy (OR 7.9; P < 0.001), and the combination of the two (OR 35.7; P < 0.001). The handwritten directive had the same impact (OR 13.3) as the formalized directive (OR 13.8). The effect of proxy opinion was slightly stronger when provided by a doctor (OR 11.3) rather than by family (OR 7.8).

Conclusion: Advance directives and proxy opinions are equally effective in influencing doctors' decisions, but having both has the strongest effect. The format of the advance directive and the identity of the proxy have little influence on decisions.
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http://dx.doi.org/10.1016/j.jpainsymman.2013.03.010DOI Listing
January 2014

[Self medication with analgesics: what are the risks?].

Rev Med Suisse 2010 Jun;6(255):1338-41

Clinique de Carouge I, Avenue Cardinal-Mermillod, 1227 Carouge.

Analgesics are among the most widely consumed drugs, whether they have been prescribed by a healthcare provider or used as self-medication. Their use can be associated with a toxicity risk, in particular in elderly patients with comorbid conditions and polypharmacy, which is synonymous with potential drug interactions. These risks are particularly high given the fact that patients are usually unaware of them, which highlights the necessity for thorough counselling and a precise drug history. In this article, we discuss the risks that are inherent to self-medication with paracetamol, nonsteroidal antiinflammatory drugs and opioids. The particular case of medication overuse headache is mentioned as an entity which is characterized by a dependency-like behaviour towards the concerned analgesics.
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June 2010

Effect of topical morphine (mouthwash) on oral pain due to chemotherapy- and/or radiotherapy-induced mucositis: a randomized double-blinded study.

J Palliat Med 2010 Feb;13(2):125-8

Division of Internal Medicine, Lucerne, Switzerland.

Purpose: The objective of the study was to determine if mouthwashes with a morphine-containing solution decrease oral pain associated with radiotherapy- and/or chemotherapy-induced oral mucositis (OM).

Methods: Randomized double-blinded crossover study to evaluate the effect of topical oral application of 2 per thousand morphine solution in patients suffering from radiotherapy- and/or chemotherapy-induced OM. Participants assigned to either the morphine solution or a placebo mouthwash received one of the solutions days 1-3 and were then switched over to the other treatment for days 4-6.

Results: Nine patients were randomized in both groups. All patients (mean age, 55.1 +/- 3.0) except one had head and neck cancers. Mean intensity of pain associated with mucosal injury (World Health Organization [WHO] mucositis > or =2) was on a 10-point visual analogue scale: 6.0 +/- 2.7). The analysis of variance (ANOVA) model that included morphine or placebo, day and time of mouthwash, and mouthwash effect shows that pain alleviation 1 hour after mouthwash was significantly influenced by the gesture of the mouthwash (p < 0.001 with either morphine or placebo) and almost by the efficiency of morphine (p = 0.020). Duration of pain relief was 123.7 (standard deviation [SD] +/- 98.2) minutes for morphine. Most other reported symptoms were present at the baseline and were probably associated with the main disease and not secondary to the morphine mouthwash.

Conclusions: Our results suggest a possible analgesic effect of topical morphine in line with previous studies. However, more efforts must be made for the adjustment of systemic analgesics and the development of new alternatives to treat locally OM-associated pain.
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http://dx.doi.org/10.1089/jpm.2009.0195DOI Listing
February 2010

Pharmacokinetic and pharmacodynamic properties of buprenorphine after a single intravenous administration in healthy volunteers: a randomized, double-blind, placebo-controlled, crossover study.

Clin Ther 2007 Aug;29(8):1620-31

Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.

Background: Buprenorphine is used as an analgesic for postoperative and chronic pain. The usual sublingual dose is 0.2 to 0.8 mg, and the usual parenteral dose is 0.3 mg for acute postoperative pain. The pharmacokinetic and related pharmacodynamic properties of buprenorphine at these doses have not been characterized.

Objective: The aim of this study was to assess the pharmacokinetic properties of buprenorphine 0.002 mg/kg IV (0.15 mg/70 kg) and its antinociceptive and psychomotor effects.

Methods: Healthy male volunteers received 0.002 mg/kg buprenorphine IV in a randomized, double-blind, placebo-controlled, crossover design. Blood samples were collected at 0.5, 1, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, and 8 hours for the determination of plasma concentrations. Pharmacokinetic parameters were estimated by a compartmental model using specialized software. Antinociceptive and psychomotor effects were determined for 8 hours. Quantitative sensory testing with thermal and electrical (nociceptive flexion RIII reflex) stimulations was performed. The cold pressor test was used to assess pain tolerance to a tonic, intense pain stimulation. Psychomotor performance was assessed by the digit symbol substitution test (DSST). Participants also rated sedation on an 11-point numeric scale (0 = none to 10 = severe). A selective liquid chromatography-tandem mass spectrometry assay was developed for the determination of buprenorphine; the limit of quantification was 0.05 ng/mL using a 0.25-mL plasma aliquot. Participants were instructed to report adverse effects, which were recorded for type, time of onset, seriousness, and duration.

Results: The study enrolled 12 participants, all of whom were white. Mean (SD) age was 26 (3.5) years, and mean weight was 67 (9) kg. None of the participants had a history of opiate abuse. Buprenorphine significantly increased the objective (nociceptive flexion RIII reflex) and subjective pain thresholds for >4 hours and pain tolerance (cold pressor test) for 2 hours. The mean (SD) RIII reflex threshold and subjective threshold at baseline were 31.6 (9.5) mA and 45.5 (22.3) mA, respectively. The maximum increases (mean [SD]) were +14.1 (17.5) mA for the RIII reflex (P = 0.02) and +24.2 (21.7) mA for the subjective threshold (P = 0.02), corresponding to mean (SEM) percentages of 53.7% (20.2%) and 74.7% (20.4%) of the baseline values, respectively. The maximum increases were observed at 120 minutes for both measures. The effect of buprenorphine on pain tolerance peaked at 30 minutes. Mean (SEM) latency before withdrawal of the hand was 69 (10) seconds, corresponding to a mean increase of 63.8% (14.4%) from baseline (P = 0.003). Buprenorphine had a significant effect on the DSST. The mean maximum decrease in the total number of symbols drawn was -6 (14.5%; P = 0.005) at 1 hour. The participants reported high levels of sedation: at peak effect (120 minutes), mean scores increased from 2.9 to 6.4 (SEM 0.7) (P = 0.005). Levels returned to baseline values by the end of the session, unlike for the nociceptive tests. The onset of effects occurred during the distribution phase for all the measures, and their duration was observed across a wide range of concentrations during the elimination phase. The most likely explanation for this finding is the high affinity of buprenorphine at mu-opioid receptors, and possibly distribution to the brain. Buprenorphine t(l/2) was 2.75 hours. A secondary peak in concentration was observed at 90 minutes, suggesting enterohepatic circulation of buprenorphine. A 2-compartment model adequately described buprenorphine pharmacokinetics.

Conclusions: A clinically relevant analgesic dose of 0.002 mg/kg (0.15 mg/70 kg) of buprenorphine had a significant effect on nociception and psychomotor performance in these healthy male volunteers. A 2-compartment model satisfactorily characterized buprenorphine pharmacokinetics, and we found evidence of enterohepatic circulation.
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http://dx.doi.org/10.1016/j.clinthera.2007.08.007DOI Listing
August 2007

National questionnaire survey on what influences doctors' decisions about admission to intensive care.

BMJ 2004 Aug;329(7463):425

Pain and Palliative Care Consultation, Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, CH-1211 Geneva 14, Switzerland.

Objective: To determine what influences doctors' decisions about admission of patients to intensive care.

Design: National questionnaire survey using eight clinical vignettes involving hypothetical patients.

Setting: Switzerland.

Participants: 402 Swiss doctors specialising in intensive care.

Main Outcome Measures: Rating of factors influencing decisions on admission and response to eight hypothetical clinical scenarios.

Results: Of 381 doctors agreeing to participate, 232 (61%) returned questionnaires. Most rated as important or very important the prognosis of the underlying disease (82%) and of the acute illness (81%) and the patients' wishes (71%). Few considered important the socioeconomic circumstances of the patient (2%), religious beliefs (3%), and emotional state (6%). In the vignettes, underlying disease (cancer versus non-cancerous disease) was not associated with admission to intensive care, but four other factors were: patients' wishes (odds ratio 3.0, 95% confidence interval 2.0 to 4.6), "upbeat" personality (2.9, 1.9 to 4.4), younger age (1.5, 1.1 to 2.2), and a greater number of beds available in intensive care (1.8, 1.2 to 2.5).

Conclusions: Doctors' decisions to admit patients to intensive care are influenced by patients' wishes and ethically problematic non-medical factors such as a patient's personality or availability of beds. Patients with cancer are not discriminated against.
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http://dx.doi.org/10.1136/bmj.329.7463.425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514202PMC
August 2004
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