Voluntary stopping of eating and drinking: is medical support ethically justified?

Background Physician-assisted dying has been the subject of extensive discussion and legislative activity both in Europe and North America. In this context, dying by voluntary stopping of eating and drinking (VSED) is often proposed, and practiced, as an alternative method of self-determined dying, with medical support for VSED being regarded as ethically and legally justified. Argument In our opinion, this view is flawed. First, we argue that VSED falls within the concept of suicide, albeit with certain unique features (non-invasiveness, initial reversibility, resemblance to the natural dying process). Second, we demonstrate, on the basis of paradigmatic clinical cases, that medically supported VSED is, at least in some instances, tantamount to assisted suicide. This is especially the case if a patient’s choice of VSED depends on the physician’s assurance to provide medical support. Conclusion Thus, for many jurisdictions worldwide, medically supported VSED may fall within the legal prohibitions on suicide assistance. Physicians, lawmakers, and societies should discuss specific ways of regulating medical support for VSED in order to provide clear guidance for both patients and healthcare professionals

Neurological Symptoms in Palliative Care Patients

Background: Neurological expertise in palliative care may be required not only for patients with primary neurological disorders but also for patients with non-neurological diseases suffering from burdensome neurological symptoms. The aim of this study was to determine the prevalence of neurological diagnoses and symptoms in palliative care patients, as well as the related burden and impact on everyday life. Methods: We analyzed retrospectively the medical records of 255 consecutive patients from a tertiary medical center, at the time point of referral to an inpatient palliative care consultation service. In addition, 100 patients prospectively answered a questionnaire which included the assessment of neurological symptoms, as well as numeric rating scales for quality of life, symptom-specific burden, and restrictions in everyday life. Results: Forty-one patients (16%) suffered from a primary neurological disease. Most decisions regarding the termination of life-sustaining measures concerned this group (20/22, 91%). Neurological symptoms (excluding pain) were documented in 122 patients (48%) with an underlying non-neurological disease. In the questionnaire study, 98/100 patients reported at least one neurological or neuropsychiatric symptom, most frequently sleeping problems (N = 63), difficulty concentrating (N = 55), and sensory symptoms (N = 50). Vertigo/dizziness (N = 19) had the greatest impact on everyday life (7.57/10 +/- 2.17) and the highest symptom-specific burden (7.14 +/- 2.51). Difficulty concentrating (restrictions in everyday life/burden) and pain intensity were the only symptoms significantly correlated with quality of life (r = -0.36, p = 0.009/r = -0.32; p = 0.04; r = -0.327, p = 0.003). Conclusion: Neurological diseases and symptoms are frequent among palliative care patients and are often associated with a high symptom burden, which may severely affect the patients' lives. It is thus of paramount importance to implement neurological expertise in palliative care

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS

Needs, expectations, and concerns of medical students regarding end-of-life issues before the introduction of a mandatory undergraduate palliative care curriculum.

BACKGROUND: In the past, implementation of effective palliative care curricula has emerged as a priority in medical education. In order to gain insight into medical students' needs and expectations, we conducted a survey before mandatory palliative care education was introduced in our faculty. METHODS: Seven hundred nine students answered a questionnaire mainly consisting of numeric rating scales (0-10). RESULTS: Participants attributed a high importance to palliative care for their future professional life (mean, 7.51 ± 2.2). For most students, symptom control was crucial (7.72 ± 2.2). However, even higher importance was assigned to ethical and legal issues (8.16 ± 1.9). "Self-reflection regarding their own role as a physician caring for the terminally ill along with psychological support" was also regarded as highly important (7.25 ± 2.4). Most students were moderately concerned at the prospect of being confronted with suffering and death (5.13 ± 2.4). This emotional distress was rated significantly higher by female students (5.4 ± 2.4 versus 4.6 ± 2.4; p < 0.001). Seventeen percent of all students rated their distress as being 7 of 10 or higher, which indicates a considerable psychological strain in terms of dealing with end-of-life issues in the future. Professional or personal experience with terminally ill persons lowered these anxieties significantly (4.99 ± 2.34 versus 5.47 ± 2.5, p < 0.05). CONCLUSIONS: Medical students stated a remarkably high interest in learning palliative care competencies. Responding to their specific concerns and needs-especially with regard to the acquisition of emotional coping skills-may be key for the development of successful palliative care curricula

Meta-analysis of VEGF variations in ALS: increased susceptibility in male carriers of the -2578AA genotype

BACKGROUND: Targeted delivery of the angiogenic factor, VEGF, to motor neurons prolongs survival in rodent models of ALS, while mice expressing reduced VEGF levels develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred an increased susceptibility to ALS in humans, but later studies challenged this initial finding. Methods and Findings: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (-2578C/A, -1154G/A and -634G/C) increase the risk of ALS. Over 7,000 individuals from 8 European and 3 American populations were included in the analysis. Pooled odds ratios were calculated using fixed and random effect models and 4 potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analyses by gender revealed, however, that the -2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR=1.46 males versus females; CI=1.19-1.80; p=7.8 10E-5), even after correction for publication bias and multiple testing. CONCLUSION: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with an increased susceptibility to ALS in male subjects reappraises the link between reduced VEGF levels and ALS, as originally revealed by the fortuitous mouse genetic studies.status: publishe

Meta-analysis of VEGF variations in ALS: increased susceptibility in male carriers of the -2578AA genotype

BACKGROUND: Targeted delivery of the angiogenic factor, VEGF, to motor neurons prolongs survival in rodent models of ALS, while mice expressing reduced VEGF levels develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred an increased susceptibility to ALS in humans, but later studies challenged this initial finding. Methods and Findings: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (-2578C/A, -1154G/A and -634G/C) increase the risk of ALS. Over 7,000 individuals from 8 European and 3 American populations were included in the analysis. Pooled odds ratios were calculated using fixed and random effect models and 4 potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analyses by gender revealed, however, that the -2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR=1.46 males versus females; CI=1.19-1.80; p=7.8 10E-5), even after correction for publication bias and multiple testing. CONCLUSION: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with an increased susceptibility to ALS in male subjects reappraises the link between reduced VEGF levels and ALS, as originally revealed by the fortuitous mouse genetic studies.status: publishe