Monica Escher

Effect of Topical Morphine (Mouthwash) on Oral Pain Due to Chemotherapy- and/or Radiotherapy-Induced Mucositis: A Randomized Double-Blinded Study

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.

Admission of incompetent patients to intensive care : Doctors' responsiveness to family wishes

Objective:When a patient is incompetent, the family is often considered to be a natural surrogate. The doctors’ responsiveness to family wishes may vary. We explored if doctors’ personal characteristics were associated with responsiveness to the relatives’ wishes when admission to the intensive care unit (ICU) is considered. Methods:In a mail survey, we asked all Swiss ICU doctors to decide on the admission of a hypothetical incompetent patient presenting with hemolytic uremic syndrome. Each participant was randomly allocated to a version of the scenario in which the family asked either that “everything be done” or that the patient be “spared useless suffering.” Main Results:Overall, 232 (60.9%) questionnaires were returned. When the family asked that “everything be done,” 60% of doctors chose to admit the hypothetical patient, but when the family asked that she be spared useless suffering, only 39% did so (odds ratio [OR] 2.6, confidence interval 1.5–4.6). This OR captures responsiveness to family wishes. It varied across subgroups of ICU doctors. Characteristics associated with greater responsiveness to family wishes were older age (OR 6.0 vs. 1.2, p = 0.002), nonuniversity work setting (OR 4.2 vs. 1.0, p = 0.012), less time devoted to intensive care practice (OR 4.0 vs. 1.5, p = 0.036), and greater self-confidence in ethical knowledge (OR 3.4 vs. 1.7, p = 0.044). Conclusions:Older doctors and those working in regional hospitals were more responsive to family wishes when assessing an incompetent patient for ICU admission. These findings emphasize the need for effective advance care planning.

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

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 6 juillet 2013

Preventive Treatments for Rheumatoid Arthritis: Issues Regarding Patient Preferences

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.

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

BackgroundVoriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.Case presentationA 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.ConclusionThe integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.

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

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.

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

Herbal remedies (HR) are used worldwide with a prevalence of use in the USA of 18 % [1]. They were shown to be the cause of 16 % of drug-induced liver injury (DILI) cases [2]. DILI was lethal in 10 % of patients and 17 % developed chronic liver injury. Both patient and drug characteristics can increase the risk of DILI. We report here the case of a severe liver injury after treatment by a HR in a patient characterized as a rapid CYP3A metabolizer. A 43-year-old woman presented 10 days after the onset of fatigue, nausea, vomiting, and jaundice. She denied consuming any alcohol or illicit drugs. She had no palmar erythema, spider nevi, or ascites that would have been suggestive of chronic liver disease and no fever. She had taken a total of five tablets of 500 mg of paracetamol during the 3 days before for headaches but no other medication. On admission, laboratory values were as follows: normal blood count, INR 1.18, AST 1971 IU/l (normal range 11–42), ALT 2940 IU/l (9–42), normal alkaline phosphatase, γ-glutamyltransferase 98 IU/l (9–35), serum bilirubin 71 μmol/l (7–25). She tested negative for hepatitis A to E as well as CMVand Epstein-Barr viruses. She had no hypergammaglobulinemia, and smooth muscle antibodies were undetectable. At abdominal ultrasonography, the liver was normal in size without biliary tract obstruction. Serum bilirubin continued to rise to 138 μmol/l (Fig. 1). A liver biopsy was performed on day 5 after admission. Histological examination revealed extensive hepatocellular necrosis predominantly lobular, with portal inflammation composed of mononuclear cells and numerous polynuclear eosinophils, focal portal vein endothelitis, and signs of cholestasis. When questioned again, the patient reported having taken one tablespoon of flower pollen daily for seasonal fatigue over a period of 3 to 4 weeks prior to the development of symptoms. Her husband collected the pollen in his fields and made the preparation, which he had previously taken without any problem. The patient received IV N-acetylcysteine and vitamin K. She left the hospital after 10 days. Liver enzymes returned to normal after 2 months. The flower pollen was analyzed. It contained a high concentration of echimidine (104.0 ± 20.8 μg/kg), a pyrrolizidine alkaloid (PA) with known hepatotoxicity. Hepatotoxicity is due to the formation of a reactive metabolite via CYP2B6 and CYP3A4 [3]. Phenotyping of CYP3Awas performed using a specific probe approach with the administration of 0.1 mg of midazolam (MDZ) and evaluation of the metabolic ration between OHmidazolam (OH-MDZ) and MDZ in the plasma [4]. The patient had a high CYP3A enzyme activity (OH-MDZ/MDZ 12.2, normal range 0.48±0.16), which may have led to increased formation of the hepatotoxic metabolite. This case of severe herbal induced liver injury underlines that herbal remedies can be harmful in susceptible individuals. High CYP3A activity was a likely risk factor in our patient, although other mechanisms may have been involved, such as a variation in CYP2B6 activity or in other detoxifying metabolic pathways. CYP3A4 expression in the liver varies widely between individuals (>100-fold). While CYP3A phenotypes are highly variable, they show a unimodal distribution [5]. * Victoria Rollason victoria.rollason@hcuge.ch

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

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.

The variety of hope: findings in palliative care patients’ medical records

There is a widespread consensus about the importance of hope for human life (Dalferth 2016). However, opinions diverge greatly when it comes to defining the essence, the function and the value of hope (Woschitz 1979). The ancient Greek culture illustrates the different perspectives on hope (elpis) eloquently: according to the Greek myth of Pandora’s Box, hope is the only blessing mankind has left to bear the toil and suffering of life. Interestingly, the ancient narrative recalls the harshness of life, and less the extraordinary human capacity not only to endure suffering, but also to make sense of it (Most 2006). A similarly negative evaluation of hope is to be found in the Greek fabulist Aesop. The moral lessons of his fables is that it is unreasonable to give up a present good – how small it may be – for the sake of something we do not have yet, i.e., we hope to get (Aesop 2008). But Theognis of Megara and the Hippocratic writings give a more favourable account of hope by stressing the supporting effect of hope. According to the Greek physician, hoping that patients recover or feel better is the doctors’ raison d’être (Gallois 2005). The following essay is an attempt to understand what hope is in the context of palliative care: wishful thinking, i.e., a reactive attitude or coping strategy to face bad news, as it is often mentioned in the literature (Shirado et al. 2013; Olsman et al. 2014; Koopman et al. 2016) an active will for something to happen, an expression of faith or trust in a beneficent transcendence, a form of inborn optimism, a positive feeling (Hilpert 2017; Wienand et al. submitted)? Sometimes we associate hope with denial of reality, for example when a person says they continue hoping for their complete recovery despite their imminent death. In a palliative care context, a similar tension is noticed time and again: despite prognosis of death, some patients and their family do not give up their hope of complete cure. But this example illustrates only one particular – and in fact relatively rare – form of hope qua wishful thinking. Yet, there is a variety of hope as our study has documented. The analysis of hope in a palliative care context should therefore be undertaken with greater interpretative caution in order to understand the patient’s inner perspective (Dalferth 2016). In other words, a preconceived opinion on hope prevents from grasping what patients and family actually mean when they speak about hope (Bühler & Peng-Keller 2014). This stumbling block drew our attention while reading and analysing 300 palliative patients’medical records collected at three Swiss university hospitals between April and September 2016. Since qualitative research design helps to investigate medical staff’s written statements about patients in more depth than quantitative research (Green and Britten 1998), we used this approach to understand patients’ perspective. More precisely, we used content analysis for analysing the data (Vaismoradi et al. 2013). Details on the data extraction sheet and data collection are described elsewhere (Rakic et al. under revision). The quotes cited in this essay are verbatim texts written by the medical team into the patients’ medical records. The passages were copied and translated from French or German into English. We obtained the ethical approval from the local research ethics committee ([EKNZ]; Nr. EK 2015–197).

Should gratitude be a requirement for access to live organ donation

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 recipients 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 donors 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.