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The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1β release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response of bladder epithelial cells during infection with uropathogenic Escherichia coli (UPEC). Human bladder epithelial cells (5637) and CRISPR/Cas9 generated caspase-1, caspase-4 and NLRP3 knockdown cells were stimulated with the UPEC strain CFT073. Using Olink proteomics and real time RT-PCR, we showed that caspase-1, caspase-4 and NLRP3 are vital for the expression of many inflammatory genes and proteins from bladder epithelial cells. When investigating the effect of inflammasome-associated proteins on neutrophils, we found that conditioned medium from UPEC-infected caspase-4 knockdown cells significantly increased phagocytosis of CFT073 and significantly decreased ROS production from neutrophils. In contrast, conditioned medium from UPEC-infected NLRP3 knockdown cells significantly decreased the phagocytosis of CFT073 and significantly increased the ROS production from neutrophils. In conclusion, we showed that the inflammasome-associated proteins contribute to the host cell response during UPEC infection.

Background Traditionally, palliative care has focused on patients suffering from life-threatening somatic diseases such as cancer or progressive neurological disorders. In contrast, despite the often chronic, severely disabling, and potentially life-threatening nature of psychiatric disorders, there are neither palliative care units nor clinical guidelines on palliative measures for patients in psychiatry. Main text This paper contributes to the growing literature on a palliative approach in psychiatry and is based on the assumption that a change of perspective from a curative to a palliative approach could help promote patient-centeredness and increase quality of life for severely ill patients in psychiatry as well as in somatic medicine. To exemplify this, we offer three different clinical scenarios: severe and enduring anorexia nervosa, treatment-refractory schizophrenia, and chronic suicidality and persistent self-injury in borderline personality disorder. Conclusion We emphasize that many typical interventions for treatment-refractory psychiatric disorders may indeed be of a palliative nature. Furthermore, introducing traditional features of palliative care, e.g. so-called goals of care conversations, could aid even further in ensuring that caregivers, patients, and families agree on which treatment goals are to be prioritized in order to optimize quality of life in spite of severe, persistent mental disorder.

The NLRP3 inflammasome, estrogen and antimicrobial peptides have all been found to have a vital role in the protection of the bladder urothelium. However, the interdependence between these protective factors during a bladder infection is currently unknown. Our aim was to investigate the role of NLRP3 in the regulation of antimicrobial peptides and estrogen signaling in bladder epithelial cells during a UPEC infection. Human bladder epithelial cells and CRISPR/Cas9-generated NLRP3-deficient cells were stimulated with the UPEC strain CFT073 and estradiol. The gene and protein expression were evaluated with microarray, qRT-PCR, western blot and ELISA. Microarray results showed that the expression of most antimicrobial peptides was reduced in CFT073-infected NLRP3-deficient cells compared to Cas9 control cells. Conditioned medium from NLRP3-deficient cells also lost the ability to suppress CFT073 growth. Moreover, NLRP3-deficient cells had lower basal release of Beta-defensin-1, Beta-defensin-2 and RNase7. The ability of estradiol to induce an increased expression of antimicrobial peptides was also abrogated in NLRP3-deficient cells. The decreased antimicrobial peptide expression might be linked to the observed reduced expression and activity of estradiol receptor beta in NLRP3-deficient cells. This study suggests that NLRP3 may regulate the release and expression of antimicrobial peptides and affect estrogen signaling in bladder epithelial cells.

Aims To examine attitudes towards physician-assisted suicide (PAS) among physicians in Sweden and compare these with the results from a similar cross-sectional study performed in 2007. Participants A random selection of 250 physicians from each of six specialties (general practice, geriatrics, internal medicine, oncology, surgery and psychiatry) and all 127 palliative care physicians in Sweden were invited to participate in this study. Setting A postal questionnaire commissioned by the Swedish Medical Society in collaboration with Karolinska Institute in Stockholm. Results The total response rate was 59.2%. Slightly fewer than half [47.1% (95% CI 43.7–50.5)] of the respondents from the six specialties accepted PAS, which is significantly more than accepted PAS in the 2007 study [34.9% (95% CI 31.5–38.3)]. Thirty-three percent of respondents were prepared to prescribe the needed drugs. When asked what would happen to the respondent’s own trust in healthcare, a majority [67.1% (95% CI 63.9–70.3)] stated that legalizing PAS would either not influence their own trust in healthcare, or that their trust would increase. This number is an increase compared to the 2007 survey, when just over half [51.9% (95% CI 48.0–55.2)] indicated that their own trust would either not be influenced, or would increase. Conclusions The study reveals a shift towards a more accepting attitude concerning PAS among physicians in Sweden. Only a minority of the respondents stated that they were against PAS, and a considerable proportion reported being prepared to prescribe the needed drugs for patient self-administration if PAS were legalized.

Objectives: Person‐centered care emphasizes patient choice and autonomy and is considered an important means for improving the quality of care and quality of life for older adults with multiple chronic conditions and functional limitations. In implementing person‐centered care, goals of care based on the patient’s preferences are considered fundamental. Psychiatry is generally practiced in a curative paradigm, and little is known about the goals of care in geriatric psychiatric settings. In this study, goals of care as documented in care plans and medical records in geriatric psychiatric outpatient care have been explored, with a special focus on the end of life. Methods: This study was based on a descriptive qualitative content analysis of medical records of patients enrolled at an outpatient clinic for geriatric psychiatry at the time of death. It was complemented by a basic quantitative analysis of patient characteristics. Results: A total of 66 medical records were included, with a male/female ratio of 41/59% and a mean age of 83 years (66–104 years). Among psychiatric diagnoses, depression predominated. The dataset was generally limited, and clearly defined goals of care were sparsely presented. Therefore, the included medical records were analyzed twice: first regarding goals of care and second regarding patient wishes and requests. In both cases, the highest level of abstraction in terms of themes was achieved. Analysis of goals of care resulted in the themes patient well‐being and care arrangements. Analysis of patient wishes resulted in the themes active patienthood and living and being. Conclusion: Goals of care were often disease‐oriented, focusing on recovery or symptom management, whereas analysis of patients’ wishes revealed personal goals other than remission, including outspoken existential needs. The results call for further research on the interplay between person‐centered care and the goal‐planning process and point to the potential of a palliative approach in geriatric psychiatric care involving patients with complex comorbidities and multilevel needs.

Women with disabilities are at increased risk of violence and neglect, and the physical and psychological barriers to seeking help often lead to prolonged periods of abuse. In addition to being a leading cause of acute injuries and numerous chronic diseases, exposure to violence also negatively affects mental health. The aim of this cross-sectional quantitative data analysis was to investigate potentially distinct experiences of violence among women with disabilities resulting from cerebral palsy (CP), multiple sclerosis (MS), traumatic brain injury (TBI), stroke, arthritis as well as isolated sensory disabilities including visual- or hearing impairment. Indeed, our data shows that type of mistreatment, perpetrators and required personal assistance differ between disability groups. Interestingly, the highest frequency of violence/abuse was observed among women with hearing impairment. Together with MS, this type of disability was also more frequently associated with denial of help with basic needs or prevented use of assistive devices comparing to the other groups. Our results provide an insight into the types of abuse characteristic for certain disability groups, which can help develop more targeted preventive strategies. Furthermore, our findings indicate that prevalence of violence in certain disability groups remains unchanged despite societal efforts, hence calling for further research and more targeted interventions to prevent mistreatment of vulnerable populations.

Background The aim of this paper is to critically discuss some of the ethically controversial issues regarding continuous deep palliative sedation at the end of life that are addressed in the EAPC recommended framework for the use of sedation in palliative care. Discussion We argue that the EAPC framework would have benefited from taking a clearer stand on the ethically controversial issues regarding intolerable suffering and refractory symptoms and regarding the relation between continuous deep palliative sedation at the end of life and euthanasia. It is unclear what constitutes refractory symptoms and what the relationship is between refractory symptoms and intolerable suffering, which in turn makes it difficult to determine what are necessary and sufficient criteria for palliative sedation at the end of life, and why. As regards the difference between palliative sedation at the end of life and so-called slow euthanasia, the rationale behind stressing the difference is insufficiently demonstrated, e.g. due to an overlooked ambiguity in the concept of intention. It is therefore unclear when palliative sedation at the end of life amounts to abuse and why. Conclusions The EAPC framework would have benefited from taking a clearer stand on some ethically controversial issues regarding intolerable suffering and refractory symptoms and regarding the relation between continuous deep palliative sedation at the end of life and euthanasia. In this text, we identify and discuss these issues in the hope that an ensuing discussion will clarify the EAPC's standpoint.

Objective: Health education programs using group learning sessions for patients with long-term conditions have been tested, but not evaluated. In order to evaluate such sessions, the purpose was to explore experiences from patients with long-term conditions after participating in group learning sessions. Methods: A descriptive design based on qualitative content analysis was used. Interviews were conducted with 19 patients with different long-term conditions, and participants were asked about their experiences after taking part in the group learning sessions. Results: Sharing experiences with one another gave them opportunities for learning. Patients described a metaphorical “expanded window,” which opens in the group learning sessions; comparable to encounters during regular visits to health care providers. The nature of the learning environment that follows the educational model, together with describing lived experiences, allowed patients to share capability and resources, which was found to be foundational. Conclusions: The health education program as a format was important for shared learning. The facilitator can support the learning by structuring the format, but most essential was sharing experiences that facilitated each patient’s learning that can aid the support of individual self-management.

Background Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient’s choices will be addressed in the current debate. Main text In this article we show how the legal and medical frameworks of Germany, Poland and Sweden differ with regard to end-of-life decisions for patients with a fatal progressive disease. Taking Amyotrophic Lateral Sclerosis (ALS) as an example, we systematically compare clinical guidelines and healthcare law, pointing out the country-specific differences most relevant for existential decision-making. A fictional case report discusses the implications of these differences for a patient with ALS living in either of the three countries. Patients with ALS in Germany, Poland and Sweden are confronted with a similar spectrum of treatment options. However, the analysis of the normative frameworks shows that the conditions for making existential decisions differ considerably in Germany, Poland and Sweden. Specifically, these differences concern (1) the legal status of advance directives, (2) the conditions under which life-sustaining therapies are started or withheld, and (3) the legal regulations on assisted dying. Conclusion According to the presented data, regulations of terminating life-sustaining treatments and the framework of “informed consent” are quite differently understood and implemented in the legal setting of the three countries. It is possible, and even likely, that these differences in the legal and medical frameworks have a considerable influence on existential decisions of patients with ALS.

Background The LUCAS™ device delivers mechanical chest compressions that have been shown in experimental studies to improve perfusion pressures to the brain and heart as well as augmenting cerebral blood flow and end tidal CO 2, compared with results from standard manual cardiopulmonary resuscitation (CPR). Two randomised pilot studies in out-of-hospital cardiac arrest patients have not shown improved outcome when compared with manual CPR. There remains evidence from small case series that the device can be potentially beneficial compared with manual chest compressions in specific situations. This multicentre study is designed to evaluate the efficacy and safety of mechanical chest compressions with the LUCAS™ device whilst allowing defibrillation during on-going CPR, and comparing the results with those of conventional resuscitation. Methods/design This article describes the design and protocol of the LINC-study which is a randomised controlled multicentre study of 2500 out-of-hospital cardiac arrest patients. The study has been registered at ClinicalTrials.gov ( http://clinicaltrials.gov/ct2/show/NCT00609778?term=LINC&rank=1 ). Results Primary endpoint is four-hour survival after successful restoration of spontaneous circulation. The safety aspect is being evaluated by post mortem examinations in 300 patients that may reflect injuries from CPR. Conclusion This large multicentre study will contribute to the evaluation of mechanical chest compression in CPR and specifically to the efficacy and safety of the LUCAS™ device when used in association with defibrillation during on-going CPR.