Perceived Burdensomeness and the Wish for Hastened Death in Persons With Severe and Persistent Mental Illness

Background: In several European countries, medical assistance in dying (MAID) is no longer confined to persons with a terminal prognosis but is also available to those suffering from persistent and unbearable mental illness. To date, scholarly discourse on MAID in this population has been dominated by issues such as decision-making capacity, uncertainty as to when a disease is incurable, stigmatization, isolation, and loneliness. However, the issue of perceived burdensomeness has received little attention. Objective: The study explores the possible impact of perceived burdensomeness on requests for MAID among persons with severe and persistent mental illness (SPMI). Method: Using the method of ethical argumentation, we discuss the issue of access to MAID for persons with SPMI and perceived burdensomeness. Conclusion: Perceived burdensomeness may be a contributing factor in the wish for hastened death among persons with SPMI. MAID is ethically unsupportable if SPMI causes the individual to make an unrealistic assessment of burdensomeness, indicating a lack of decision-making capacity in the context of that request. However, the possibility that some individuals with SPMI may perceive burdensomeness does not mean that they should be routinely excluded from MAID. For SPMI patients with intact decision-making capacity who feel their life is not worth living, perceived burdensomeness as a component of this intolerable suffering is not a sufficient reason to deny access to MAID

Scanning reflectance spectroscopy (380-730nm): a novel method for quantitative high-resolution climate reconstructions from minerogenic lake sediments

High-resolution (annual to sub-decadal) quantitative reconstructions of climate variables are needed from a variety of paleoclimate archives across the world to place current climate change in the context of long-term natural climate variability. Rapid, high-resolution, non-destructive scanning techniques are required to produce such high-resolution records from lake sediments. In this study we explored the potential of scanning reflectance spectroscopy (VIS-RS; 380-730nm) to produce quantitative summer temperature reconstructions from minerogenic sediments of proglacial, annually laminated Lake Silvaplana, in the eastern Swiss Alps. The scanning resolution was 2mm, which corresponded to sediment deposition over 1-2years. We found correlations up to r=0.84 (p<0.05) for the calibration period 1864-1950, between six reflectance-dependent variables and summer (JJAS) temperature. These reflectance-dependent variables (e.g. slope of the reflectance 570/630nm, indicative of illite, biotite and chlorite; minimum reflectance at 690nm indicative of chlorite) indicate the mineralogical composition of the clastic sediments, which is, in turn, related to climate in the catchment of this particular proglacial lake. We used multiple linear regression (MLR) to establish a calibration model that explains 84% of the variance of summer (JJAS) temperature during the calibration period 1864-1950. We then applied the calibration model downcore to develop a quantitative summer temperature reconstruction extending back to AD 1177. This temperature reconstruction is in good agreement with two independent temperature reconstructions based on documentary data that extend back to AD 1500 and tree ring data that extend back to AD 1177. This study confirms the great potential of in situ scanning reflectance spectroscopy as a novel non-destructive technique to rapidly acquire high-resolution quantitative paleoclimate information from minerogenic lake sediment

Association between Disease Severity, Heart Rate Variability (HRV) and Serum Cortisol Concentrations in Horses with Acute Abdominal Pain

Heart rate variability (HRV) is a noninvasive technique to detect changes in the autonomous nervous system. It has rarely been investigated in horses with colic. Therefore, the objective was to assess the evolution of HRV parameters and cortisol concentrations in horses with colic. The 43 horses included in this study were categorized into three groups according to the treatment (1, surgical; 2, conservative; 3, euthanized). The HRV and laboratory variables were measured at admission (T1), the day after admission (T2), and at discharge (T3) and compared between groups and over time with an ANOVA with Bonferroni correction. Relationships between the HRV parameters themselves and the laboratory variables was assessed by Pearson correlation coefficients. Evolution of the heart rate (HR) over time, mean normal to normal R intervals (meanNN) and cortisol concentrations indicate a decreased sympathetic stimulation over time in group 1 and 2, in contrast to group 3. For group 3, the meanNN and HR differed significantly to group 2 at T1 and to group 1 and 2 at T2. Treatment induced a change in the HRV and cortisol response in horses managed conservatively or surgically but not in horses that required euthanasia. However, further studies are required to assess the validity of HRV analyses in horses with colic

Pulmonary Histoplasmosis Mimicking Metastatic Lung Cancer: A Case Report.

Histoplasmosis is a well-known endemic fungal infection but experience in non-endemic regions is often limited, which may lead to delayed diagnosis and extensive testing. The diagnosis can be especially challenging, typically when the disease first presents with pulmonary nodules accompanied by hilar and mediastinal lymphadenopathy, suggesting a much more common malignant disease. In this situation, a greater FDG uptake in draining lymph nodes in comparison with the associated lung nodule seen in [ &lt;sup&gt;18&lt;/sup&gt; F]FDG-PET/CT, the so-called "flip-flop fungus" sign, can help to orientate further diagnostic measures. We report a case of a 56-year-old woman living in Switzerland, a non-endemic region, whose diagnosis of imported histoplasmosis was delayed since the findings had been initially misinterpreted as pulmonary malignancy. Further, histological workup was inconclusive due to lack of specific fungal staining, leading to ineffective treatment and non-resolving disease. This paper intends to highlight the pitfalls in diagnosing Histoplasma capsulatum and presents images of particularities of fungal infections in [ &lt;sup&gt;18&lt;/sup&gt; F]FDG-PET/CT, which in our case showed a "flip-flop fungus" sign

Palliative psychiatry in a narrow and in a broad sense: A concept clarification

Even with optimal treatment, some persons with severe and persistent mental illness do not achieve a level of mental health, psychosocial functioning and quality of life that is acceptable to them. With each unsuccessful treatment attempt, the probability of achieving symptom reduction declines while the probability of somatic and psychological side effects increases. This worsening benefit-harm ratio of treatment aiming at symptom reduction has motivated calls for implementing palliative approaches to care into psychiatry (palliative psychiatry). Palliative psychiatry accepts that some cases of severe and persistent mental illness can be irremediable and calls for a careful evaluation of goals of care in these cases. It aims at reducing harm, relieving suffering and thus improving quality of life directly, working around irremediable psychiatric symptoms. In a narrow sense, this refers to patients likely to die of their severe and persistent mental illness soon, but palliative psychiatry in a broad sense is not limited to end-of-life care. It can - and often should - be integrated with curative and rehabilitative approaches, as is the gold standard in somatic medicine. Palliative psychiatry constitutes a valuable addition to established non-curative approaches such as rehabilitative psychiatry (which focuses on psychosocial functioning instead of quality of life) and personal recovery (a journey that persons living with severe and persistent mental illness may undertake, not necessarily accompanied by mental health care professionals). Although the implementation of palliative psychiatry is met with several challenges such as difficulties regarding decision-making capacity and prognostication in severe and persistent mental illness, it is a promising new approach in caring for persons with severe and persistent mental illness, regardless of whether they are at the end of life. Keywords: Severe and persistent mental illness; end of life; futility; goals of care; irremediability; palliative psychiatry; quality of life; sufferin

The notion of free will and its ethical relevance for decision-making capacity.

Obtaining informed consent from patients is a moral and legal duty and, thus, a key legitimation for medical treatment. The pivotal prerequisite for valid informed consent is decision-making capacity of the patient. Related to the question of whether and when consent should be morally and legally valid, there has been a long-lasting philosophical debate about freedom of will and the connection of freedom and responsibility. The scholarly discussion on decision-making capacity and its clinical evaluation does not sufficiently take into account this fundamental debate. It is contended that the notion of free will must be reflected when evaluating decision-making capacity. Namely, it should be included as a part of the appreciation-criterion for decision-making capacity. The argumentation is mainly drawn on the compatibilism of Harry Frankfurt. A solution is proposed which at the same time takes the notion of free will seriously and enriches the traditional understanding of decision-making capacity, strengthening its justificatory force while remaining clinically applicable

Genomics of the new species Kingella negevensis: diagnostic issues and identification of a locus encoding a RTX toxin.

Kingella kingae, producing the cytotoxic RTX protein, is a causative agent of serious infections in humans such as bacteremia, endocarditis and osteoarticular infection, especially in young children. Recently, Kingella negevensis, a related species, has been isolated from the oral cavity of healthy children. In this study, we report the isolation of K. negevensis strain eburonensis, initially misidentified as K. kingae with MALDI-TOF MS, from a vaginal specimen of a patient suffering of vaginosis. The genome sequencing and analysis of this strain together with comparative genomics of the Kingella genus revealed that K. negevensis possesses a full homolog of the rtx operon of K. kingae involved in the synthesis of the RTX toxin. We report that a K. kingae specific diagnostic PCR, based on the rtxA gene, was positive when tested on K. negevensis strain eburonensis DNA. This cross-amplification, and risk of misidentification, was confirmed by in silico analysis of the target gene sequence. To overcome this major diagnostic issue we developed a duplex real-time PCR to detect and distinguish K. kingae and K. negevensis. In addition to this, the identification of K. negevensis raises a clinical issue in term of pathogenic potential given the production of a RTX hemolysin

Identification and Characterization of Mediators of Fluconazole Tolerance in Candida albicans.

Candida albicans is an important human pathogen and a major concern in intensive care units around the world. C. albicans infections are associated with a high mortality despite the use of antifungal treatments. One of the causes of therapeutic failures is the acquisition of antifungal resistance by mutations in the C. albicans genome. Fluconazole (FLC) is one of the most widely used antifungal and mechanisms of FLC resistance occurring by mutations have been extensively investigated. However, some clinical isolates are known to be able to survive at high FLC concentrations without acquiring resistance mutations, a phenotype known as tolerance. Mechanisms behind FLC tolerance are not well studied, mainly due to the lack of a proper way to identify and quantify tolerance in clinical isolates. We proposed here culture conditions to investigate FLC tolerance as well as an easy and efficient method to identity and quantify tolerance to FLC. The screening of C. albicans strain collections revealed that FLC tolerance is pH- and strain-dependent, suggesting the involvement of multiple mechanisms. Here, we addressed the identification of FLC tolerance mediators in C. albicans by an overexpression strategy focusing on 572 C. albicans genes. This strategy led to the identification of two transcription factors, CRZ1 and GZF3. CRZ1 is a C2H2-type transcription factor that is part of the calcineurin-dependent pathway in C. albicans, while GZF3 is a GATA-type transcription factor of unknown function in C. albicans. Overexpression of each gene resulted in an increase of FLC tolerance, however, only the deletion of CRZ1 in clinical FLC-tolerant strains consistently decreased their FLC tolerance. Transcription profiling of clinical isolates with variable levels of FLC tolerance confirmed a calcineurin-dependent signature in these isolates when exposed to FLC