Dynamic association between suicidal ambivalence and suicide risk among individuals with a history of suicide attempts.

OBJECTIVE: Suicide risk is highly fluctuating. There is a need for predictors of short-term change in suicide risk to optimize risk assessment and treatment, especially among individuals who already attempted suicide. METHODS: Based on 1776 daily assessments of 16 former psychiatric inpatients with a history of suicide attempts, we examined how suicidal ambivalence and, respectively, wish to die (WTD) and wish to live (WTL) predicted same-day and change in perceived suicide risk (i.e., next-day perceived suicide risk, controlled for same-day perceived suicide risk) in multilevel regression models. Additionally, based on the assumptions of nonlinear dynamics, we examined the associations between levels of fluctuations in the WTD/WTL and perceived suicide risk within the same time period. RESULTS: Suicidal ambivalence, WTD, and a WTL significantly correlated with same-day suicide risk. Suicidal ambivalence and WTD significantly predicted change in suicide risk. Fluctuations in WTD were significantly associated with concurrent suicide risk. CONCLUSION: The results suggest that suicidal ambivalence and WTD are drivers of suicide risk among individuals who already attempted suicide. The association between fluctuations in WTD and suicide risk was small and warrants further investigation on the practical utility as a warning sign.

'I secretly wish. . .' Caregivers' expression of wish for death of persons with severe dementia.

BACKGROUND: Qualitative evidence suggests that caregivers may express a wish for death of persons with severe dementia (PwSD). No study has assessed the extent to which it happens, stability of this wish over time and the factors associated with it. OBJECTIVES: We examined caregivers' wish for death of PwSDs overtime and the factors associated with this wish. METHODS: 215 caregivers of community dwelling PwSDs were surveyed every 4 months for 2 years. Using the mixed-effects multinomial regression model, we assessed the PwSD and caregiver factors associated with caregivers' wish for PwSDs' death. RESULTS: At baseline, 27% caregivers expressed a wish for PwSDs' life to end sooner. Overall, 43% of the caregivers expressed a wish for PwSDs' death at least once during the study period and 11% expressed it consistently. Caregivers' perception of PwSDs' lower quality of life (RRR: 1.05, 95% CI: 1.00, 1.10), higher functional dependency (RRR: 1.1, 95% CI: 1.01, 1.21), eating difficulty (RRR: 2.25, 95% CI: 1.26, 4.04) and suffering (RRR: 1.92, 95% CI: 1.05, 3.52) were associated with this wish. Caregivers who were emotionally close to PwSDs were less likely (RRR: 0.25, 95% CI: 0.11, 0.55) while those who understood that dementia is a terminal illness were more likely (RRR: 2.01, 95% CI: 1.03, 3.92) to express this wish. CONCLUSION: Caregivers' wish for PwSDs' death changed over time and was primarily driven by their perception of PwSDs' poor well-being and awareness of their illness being terminal, indicating a need for increased support in this challenging caregiving context.

[The provision of assisted death in the context of the desire to anticipate death]. / La prestación de ayuda a morir en el contexto del deseo de anticipar la muerte.

The entry into force of the Organic Law on the Regulation of Euthanasia in June 2021 obliges clinicians to reconsider their professional work, in the face of a new service that expands the limits of what was considered correct until then. This new service affects the entire healthcare system, but especially primary care professionals. Beyond the procedural and moral aspects, it is necessary to rethink the assessment of the patient who expresses a wish to die. In this review, we start with the relatively recent definition of the wish to hasten death (WTHD), its causes, epidemiology and differential diagnosis. Then, we examine the different mental frameworks found in the process of dying and the concept of a «good death¼. Finally, we analyse the paths that can lead to the provision of aid in dying within the framework of current legislation. The WTHD is specific to requests in case of «serious and advanced illness¼, not in other cases contemplated by the Law. When faced with a request to activate the Aid in Dying Prestation in the context of WTHD (that is, in the proximity of death), it becomes necessary to increase the patient's sense of control and begin to work on grief. Besides, in the face of an administrative process that will necessarily be long, adapting the therapeutic efforts and sedation should be considered as possible options. We understand that it is essential not to create false expectations for patients/families and not to overload healthcare professionals with administrative tasks that will be futile. It is difficult to balance these in the face of a request for a right to which the patient should always have access.

The state of transience, and its influence on the wish to die of advanced disease patients: insights from a qualitative phenomenological study.

BACKGROUND: The experience of Wish to Die is common in patients living with Advanced Disease. It has been studied worldwide and qualitative studies have contributed to the understanding of the complexity of the phenomenon of the WTD but a deeper understanding on the individual's views is still needed. The objective of this study was to identify common characteristics of the experience of wish to die in advanced disease. METHODS: A phenomenological study was carried out with multicenter participation of patients with advanced disease who had expressed their wish to die to health professionals. Semi-structured interviews were employed to obtain an in-depth perspective of each patient's lived experience. A phenomenological analysis of the data collected was performed to describe and explore the characteristic aspects of the phenomenon under study. RESULTS: Fourteen patients with advanced disease were interviewed. Most of them had cancer. In the analysis of the patients' accounts of their experiences, three common characteristics were identified: a) experiencing a state of transience; b) the attempt to reconnect with oneself; and c) additional disease-related aspects that influence the wish to die. Patients expressed the need for a safe space to address the wish to die and the importance of receiving care that considers both 'being' and 'doing'. CONCLUSIONS: Patients with advanced disease and wish to die experience a state of transience where the patient lives and ephemeral state of existence. Interventions focused on reinforcing the intrinsic value of the individual emerge as essential components of a compassionate accompaniment of those facing the wish to die.

A bioethical perspective on the meanings behind a wish to hasten death: a meta-ethnographic review.

BACKGROUND: The expressions of a "wish to hasten death" or "wish to die" raise ethical concerns and challenges. These expressions are related to ethical principles intertwined within the field of medical ethics, particularly in end-of-life care. Although some reviews were conducted about this topic, none of them provides an in-depth analysis of the meanings behind the "wish to hasten death/die" based specifically on the ethical principles of autonomy, dignity, and vulnerability. The aim of this review is to understand if and how the meanings behind the "wish to hasten death/die" relate to and are interpreted in light of ethical principles in palliative care. METHODS: We conducted a meta-ethnographic review according to the PRISMA guidelines and aligned with Noblit and Hare's framework. Searches were performed in three databases, Web of Science, PubMed, CINAHL, with no time restrictions. Original qualitative studies exploring the meanings given by patients, family caregivers and healthcare professionals in any context of palliative and end-of-life care were included. A narrative synthesis was undertaken. PROSPERO registration CRD42023360330. RESULTS: Out of 893 retrieved articles, 26 were included in the analysis, accounting for the meanings of a total of 2,398 participants. Several factors and meanings associated with the "wish to hasten death" and/or "wish to die" were identified and are mainly of a psychosocial and spiritual nature. The ethical principles of autonomy and dignity were the ones mostly associated with the "wish to hasten death". Ethical principles were essentially inferred from the content of included articles, although not explicitly stated as bioethical principles. CONCLUSIONS: This meta-ethnographic review shows a reduced number of qualitative studies on the "wish to hasten death" and/or "wish to die" explicitly stating ethical principles. This suggests a lack of bioethical reflection and reasoning in the empirical end-of-life literature and a lack of embedded ethics in clinical practice. There is a need for healthcare professionals to address these topics compassionately and ethically, taking into account the unique perspectives of patients and family members. More qualitative studies on the meanings behind a wish to hasten death, their ethical contours, ethical reasoning, and implications for clinical practice are needed.

Driving factors in treatment decision-making of patients seeking medical assistance for infertility: a systematic review.

BACKGROUND: ART differs in effectiveness, side-effects, administration, and costs. To improve the decision-making process, we need to understand what factors patients consider to be most important. OBJECTIVE AND RATIONALE: We conducted this systematic review to assess which aspects of ART treatment (effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood) are most important in the decision-making of patients with an unfulfilled wish to have a child. SEARCH METHODS: We searched studies indexed in Embase, PubMed, PsycINFO, and CINAHL prior to November 2023. Discrete choice experiments (DCEs), surveys, interviews, and conjoint analyses (CAs) about ART were included. Studies were included if they described two or more of the following attributes: effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood.Participants were men and women with an unfulfilled wish to have a child. From each DCE/CA study, we extracted the beta-coefficients and calculated the relative importance of treatment attributes or, in case of survey studies, extracted results. We assessed the risk of bias using the rating developed by the Grading of Recommendations Assessment, Development and Evaluation working group. Attributes were classified into effectiveness, safety, burden, costs, patient-centeredness, genetic parenthood, and others. OUTCOMES: The search identified 938 studies of which 20 were included: 13 DCEs, three survey studies, three interview studies, and one conjoint analysis, with a total of 12 452 patients. Per study, 47-100% of the participants were women. Studies were assessed as having moderate to high risk of bias (critical: six studies, serious: four studies, moderate: nine studies, low: one study). The main limitation was the heterogeneity in the questionnaires and methodology utilized. Studies varied in the number and types of assessed attributes. Patients' treatment decision-making was mostly driven by effectiveness, followed by safety, burden, costs, and patient-centeredness. Effectiveness was rated as the first or second most important factor in 10 of the 12 DCE studies (83%) and the relative importance of effectiveness varied between 17% and 63%, with a median of 34% (moderate certainty of evidence). Of eight studies evaluating safety, five studies valued safety as the first or second most important factor (63%), and the relative importance ranged from 8% to 35% (median 23%) (moderate certainty of evidence). Cost was rated as first or second most important in five of 10 studies, and the importance relative to the other attributes varied between 5% and 47% (median 23%) (moderate certainty of evidence). Burden was rated as first or second by three of 10 studies (30%) and the relative importance varied between 1% and 43% (median 13%) (low certainty of evidence). Patient-centeredness was second most important in one of five studies (20%) and had a relative importance between 7% and 24% (median 14%) (low certainty of evidence). Results suggest that patients are prepared to trade-off some effectiveness for more safety, or less burden and patient-centeredness. When safety was evaluated, the safety of the child was considered more important than the mother's safety. Greater burden (cycle cancellations, number of injections, number of hospital visits, time) was more likely to be accepted by patients if they gained effectiveness, safety, or lower costs. Concerning patient-centeredness, information provision and physician attitude were considered most important, followed by involvement in decision-making, and treatment continuity by the same medical professional. Non-genetic parenthood did not have a clear impact on decision-making. WIDER IMPLICATIONS: The findings of this review can be used in future preference studies and can help healthcare professionals in guiding patients' decision-making and enable a more patient-centered approach.

Definition and validation of the nursing diagnosis label "wish to die": a research protocol.

BACKGROUND: Euthanasia has been incorporated into the health services of seven countries. The legalisation of these practices has important repercussions for the competences of nurses, and it raises questions about their role. When a patient with advanced disease expresses a wish to die, what is expected of nurses? What are the needs of these patients, and what kind of care plan do they require? What level of autonomy might nurses have when caring for these patients? The degree of autonomy that nurses might or should have when it comes to addressing such a wish and caring for these patients has yet to be defined. Recognising the wish to die as a nursing diagnosis would be an important step towards ensuring that these patients receive adequate nursing care. This study-protocol aims to define and validate the nursing diagnosis wish to die in patients with advanced disease, establishing its defining characteristics and related factors; to define nursing-specific interventions for this new diagnosis. METHODS: A prospective three-phase study will be carried out. Phase-A) Foundational knowledge: an umbrella review of systematic reviews will be conducted; Phase-B) Definition and validation of the diagnostic nomenclature, defining characteristics and related factors by means of an expert panel, a Delphi study and application of Fehring's diagnostic content validation model; Phase-C) Definition of nursing-specific interventions for the new diagnosis. At least 200 academic and clinical nurses with expertise in the field of palliative care or primary health care will be recruited as participants across the three phases. DISCUSSION: The definition of the wish to die as a nursing diagnosis would promote greater recognition and autonomy for nurses in the care of patients who express such a wish, providing an opportunity to alleviate underlying suffering through nursing-specific interventions and drawing attention to the needs of patients with advanced disease. The new diagnosis would be an addition to nursing science and would provide a framework for providing care to people with advanced disease who express such a wish. Nurses would gain professional autonomy about identifying, exploring and responding clinically to such a wish.

Circadian Activity Rhythms and Psychopathology in Major Depressive Episodes.

BACKGROUND: Identifying suicidal risk based on clinical assessment is challenging. Suicidal ideation fluctuates, can be downplayed or denied, and seems stigmatizing if divulged. In contrast, vitality is foundational to subjectivity in being immediately conscious before reflection. Including its assessment may improve detection of suicidal risk compared to relying on suicidal ideation alone. We hypothesized that objective motility measures would be associated with vitality and enhance assessment of suicidal risk. METHODS: We evaluated 83 adult-psychiatric outpatients with a DSM-5 bipolar (BD) or major depressive disorder (MDD): BD-I (n = 48), BD-II (20), and MDD (15) during a major depressive episode. They were actigraphically monitored continuously over 3 weekdays and self-rated their subjective states at regular intervals. We applied cosinor analysis to actigraphic data and analyzed associations of subjective psychopathology measures with circadian activity parameters. RESULTS: Actigraphic circadian mesor, amplitude, day- and nighttime activity were lower with BD versus MDD. Self-rated vitality (wish-to-live) was significantly lower, self-rated suicidality (wish-to-die) was higher, and their difference was lower, with BD versus MDD. There were no other significant diagnostic differences in actigraphic sleep parameters or in self-rated depression, dysphoria, or anxiety. By linear regression, the difference between vitality and passive suicidal ideation was strongly positively correlated with mesor (p < 0.0001), daytime activity (p < 0.0001), and amplitude (p = 0.001). CONCLUSIONS: Higher circadian activity measures reflected enhanced levels of subjective vitality and were associated with lesser suicidal ideation. Current suicidal-risk assessment might usefully include monitoring of motility and vitality in addition to examining negative affects and suicidal thinking.

Go Wish card game-exploring end-of-life wishes of patients in oncology palliative care: a qualitative study.

BACKGROUND: Among the methods that promote quality of life and care, discussing and remembering end-of-life (EOL) wishes for future care may contribute to decision-making about care and the promotion of a good death. Our aim was to investigate the most significant EOL desires among Brazilian cancer patients receiving palliative care (PC). METHODS: This was an exploratory, descriptive, and qualitative study conducted in a Palliative Care Oncology Unit. Fifteen patients played the Go Wish card game (GWCG), choosing and categorizing cards into themes as very important, more or less important, and not important at all. The ten most important cards were discussed, and categories were defined for each card. Cards with the highest frequencies of choice were described. Patients were also asked, "What did playing the cards mean to you?". All data were analyzed using Bardin's content analysis and generated a word cloud to interpret the participants' narratives. RESULTS: Out of the 36 cards, card 19, "I want my family and friends close to me", was the most frequently chosen. Out of the 15 patients studied, only one reported that they initially did not enjoy playing the cards. In this study, the GWCG was effective in fulfilling 90% of the patients' wishes, and this was only possible with the support of the researchers, members of the multi-professional team, and patients' families. CONCLUSIONS: The use of the GWCG in the oncology PC setting made an important contribution to open discussions about patients' values and preferences, as well as being an easy-to-use, understandable, and flexible tool. Prioritizing the fulfillment of patients' wishes was one of the main strengths of this study. Our study suggests working with these wishes as a framework for person-centered care.

How strong is the will-to-live in frail older persons? A survey study in acute geriatric wards and nursing homes in Belgium.

INTRODUCTION: Will-to-live is defined as the psychological expression of one's commitment to life and the desire to continue living. It is an important indicator of subjective wellbeing. This study aimed to assess the will-to-live in frail older hospitalized patients and nursing home residents as well as to evaluate its association with physical frailty, tiredness of life, depression and wish-to-die. METHODS: Between March and September 2021, we interviewed 186 older adults in six nursing homes and two acute geriatric wards across Belgium. Will-to-live was assessed using a single-item numeric rating scale from 0 to 5. A linear regression analysis was performed to assess the association between will-to-live and frailty (Clinical Frailty Scale) with adjustment for age, gender and setting. Mann-Whitney U test was used to evaluate the association between will-to-live and depression, tiredness of life and wish-to-die. RESULTS: Mean age was 85 (± 6.2) years. Mean score on the Clinical Frailty Scale was five (± 1.5) and four on the will-to-live (± 1.3). No statistical significant association was found between will-to-live and age (p = 0.991), gender (p = 0.272), setting (p = 0.627) and frailty (p = 0.629). Multiple linear regression showed no significant association with Clinical Frailty Scale (p = 0.660), after adjustment for age, gender and setting. Will-to-live was negatively associated with tiredness of life (p = 0.020) and wish-to-die (p < 0.001), but not with depression (p = 0.186). DISCUSSION: Both nursing home residents and older hospitalized patients expressed a strong or very strong will-to-live. Will-to-live was not associated with physical frailty as measured by the Clinical Frailty Scale. Nursing home residents with a weak will-to-live were more likely to have depressive symptoms. Most nursing home residents with a wish-to-die had also a low will-to-live, although some residents had both a high will-to-live and wish-to-die.

Whole-Mount In Situ Hybridization in Large Sexual Schmidtea mediterranea.

Whole-mount in situ hybridization (WISH), colorimetric or fluorescent (FISH), allows for the visualization of endogenous RNA. For planarians, robust WISH protocols exist for small-sized animals (>5 mm) of the model species Schmidtea mediterranea and Dugesia japonica. However, the sexual strain of Schmidtea mediterranea studied for germline development and function reaches much larger body sizes in excess of 2 cm. The existing whole-mount WISH protocols are not optimal for such large specimens, owing to insufficient tissue permeabilization. Here, we describe a robust WISH protocol for 12-16 mm long sexually mature Schmidtea mediterranea individuals that could serve as a starting point for adapting WISH to other large planarian species.

Colorimetric Whole-Mount In Situ Hybridization in Planarians.

Whole-mount in situ hybridization (WISH) is an extremely useful technique for visualizing specific mRNA targets and solving many biological questions. In planarians, this method is really valuable, for example, for determining gene expression profiles during whole-body regeneration and analyzing the effects of silencing any gene to determine their functions. In this chapter, we present in detail the WISH protocol routinely used in our lab, using a digoxigenin-labelled RNA probe and developing with NBT-BCIP. This protocol is basically that already described in Currie et al. (EvoDevo 7:7, 2016), which put together several modifications developed from several laboratories in recent years that improved the original protocol developed in the laboratory of Kiyokazu Agata in 1997. Although this protocol, or slight modifications of it, is the most common protocol in the planarian field for NBT-BCIP WISH, our results show that key steps such as the use and time of NAC treatment to remove the mucus need to be taken into account depending on the nature of the gene analyzed, especially for the epidermal markers.

Within-person change in patient-reported outcomes and their association with the wish to undergo joint surgery during a digital first-line intervention for osteoarthritis.

AIM: To study the association between within-person changes in patient-reported outcomes (PROMs) and wish for joint surgery during participation in a digital first-line intervention comprising exercise and education for knee/hip osteoarthritis (OA). METHODS: Retrospective observational registry study. Participants enrolled between June 1, 2018 and October 30, 2021, with follow-up data at three months (n = 13,961). We used asymmetric fixed effect (conditional) logistic regressions to study the association between change in wish to undergo surgery at last available time point (3, 6, 9, or 12 months) and improvement or worsening of PROMs pain (0-10), quality of life (QoL) (EQ5D-5L, 0.243-0.976), overall health (0-10), activity impairment (0-10), walking difficulties (yes/no), fear of movement (yes/no), and Knee/Hip injury and Osteoarthritis Outcome Score 12 Items (KOOS-12/HOOS-12, 0-100) function and QoL subscales. RESULTS: The proportion of participants wishing to undergo surgery declined by 2% (95% CI: 1.9, 3.0), from 15.7% at the baseline to 13.3% at 3 months. Generally, improvements in PROMs were associated with reduced likelihood of wishing for surgery, while worsening was associated with increased likelihood. For pain, activity impairment EQ-5D and KOOS/HOOS QoL, a worsening led to a change in the probability of wish for surgery of larger absolute magnitude than an improvement in the same PROM. CONCLUSIONS: Within-person improvements in PROMs are associated with reduced wish for surgery while worsenings with an increased wish for surgery. Larger improvements in PROMs may be needed to match the magnitude of the change in wish for surgery associated with a worsening in the same PROM.

Healthy Diets from Sustainable Food Systems: Calculating the WISH Scores for Women in Rural East Africa.

Diets should be healthy for the benefits of both humans and the environment. The World Index for Sustainability and Health (WISH) was developed to assess both diets' healthiness and environmental sustainability, and the index was applied in this study. Food intake quantities for single foods were calculated based on the data collected from four 24-h recalls during two seasons in 2019/2020 with women of reproductive age in two rural areas each in Kenya, Tanzania and Uganda (n = 1152). Single foods were grouped into 13 food groups, and the amount of each food group consumed was converted to an overall WISH score and four sub-scores. The food groups with a low WISH score were fruits, vegetables, dairy foods, fish, unsaturated oils and nuts, meaning that their consumption was outside the recommended range for a healthy and sustainable diet. Contrariwise, the intake of red meat and poultry was partly above the recommended intake for those women who consumed them. The overall WISH score and sub-scores showed that the consumption of "protective" food groups needed to increase in the study population, while the consumption of "limiting" food groups was sufficient or should decrease. For future application, we recommend dividing food groups that are critical for nutrition, e.g., vegetables, into sub-groups to further understand their contribution to this index.

Validation of the Mexican version of the Schedule of Attitudes Toward Hastened Death in patients undergoing palliative care in Mexico.

OBJECTIVES: The Schedule of Attitudes Toward Hastened Death (SAHD) has emerged as a valid and reliable tool to assess the wish to hasten death (WTHD) among patients diagnosed with advanced cancer; however, the instrument has never been culturally adapted and validated for patients in Mexico. This study sought to validate and abbreviate the SAHD tool for use among patients attending the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico. METHODS: The SAHD was culturally adapted from a previously published validation in patients from Spain. Eligible patients included Spanish literate subjects treated as outpatients in the Palliative Care Service, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Patients were asked to answer the Mexican version of SAHD (SAHD-Mx) instrument and the Brief Edinburgh Depression Scale (BEDS). RESULTS: A total of 225 patients were included in the study. Median positive response in the SAHD-Mx was 2 (range 0-18). Positive correlation was identified between the SAHD-Mx scale and ECOG performance status (r = 0.188, p = 0.005), as well as BEDS (r = 0.567, p < 0.001). SAHD-Mx displayed strong internal consistency (alpha = 0.85) and adequate reliability from test-retest phone interviews (r = 0.567, p < 0.001). Using the confirmatory factor analysis model, a factor was identified and the number of items was reduced to 6, including items 4, 5, 9, 10, 13, and 18. SIGNIFICANCE OF RESULTS: The SAHD-Mx emerges as an adequate tool, with appropriate psychometric characteristics, for assessing WTHD among patients diagnosed with cancer undergoing palliative care in Mexico. .

The Temporal Dynamics of Wish to Live, Wish to Die, and Their Short-Term Prospective Relationships With Suicidal Desire.

The internal debate hypothesis (Kovacs & Beck, 1977) suggests that those at risk for suicidal thoughts and behaviors may experience fluctuations in both the wish to live (WTL) and wish to die (WTD). Previous research has investigated this hypothesis using various cross-sectional (Goods et al., 2019 [cf. Page & Stritzke, 2020]) and longitudinal methodologies (e.g., Bryan et al., 2016). No investigations have determined the within-day temporal dynamics of WTL and WTD using ecological moment assessment (EMA), however. N = 49 undergraduate university students recruited from a research participant pool from a large southeastern university in the United States with a lifetime history of suicide ideation completed the current 10-day EMA investigation. Results demonstrated that WTL, WTD, and resulting suicidal ambivalence (i.e., relatively equal WTL/WTD ratings) demonstrated similar within-person person variability; however, WTD scores appeared to demonstrate higher average variability compared to WTL and ambivalence scores. Although state WTL and WTD were concurrently related to state suicidal desire, only WTD prospectively predicted suicidal desire when controlling for the influence of the outcome variable at the previous timepoint. Ambivalence scores also prospectively predicted suicidal desire when controlling for suicidal desire at the previous timepoint. Results support the clinical and theoretical utility of separate WTL and WTD assessment. WTD was relatively stable within this sample but may be closely related to risk for future suicidal thinking. Changes in WTL may reduce state risk for suicidal desire but could be more trait-like in nature compared to WTD. Future research that investigates these hypotheses should consider the study limitations outlined.

Leptomeningeal Carcinomatosis and Palliative Care: A Case Report.

Leptomeningeal carcinomatosis (LC) is a rare but serious complication of cancer in which cancer cells spread to the leptomeninges, the membranes that surround the brain and spinal cord. The diagnosis and treatment of LC can be challenging due to the non-specific symptoms and the difficulty of accessing the leptomeninges for a biopsy. In this case report, we describe a patient with advanced breast cancer who was diagnosed with LC and underwent treatment with chemotherapy. Despite aggressive treatment, the patient's condition worsened over time, and she was referred to palliative care, where adequate symptom control was achieved, and she was discharged to her home country as per her wish. Our case highlights the difficulties associated with the diagnosis and treatment of LC and the need for continued research to improve outcomes for patients with this condition. It specifically highlights the approach a palliative care team can take for this condition.

Regulation of branched versus linear Arp2/3-generated actin filaments.

Activation of the Arp2/3 complex by VCA-motif-bearing actin nucleation-promoting factors results in the formation of "daughter" actin filaments branching off the sides of pre-existing "mother" filaments. Alternatively, when stimulated by SPIN90, Arp2/3 directly nucleates "linear" actin filaments. Uncovering the similarities and differences between these two mechanisms is fundamental to understanding how actin cytoskeleton dynamics are regulated. Here, analysis of individual filaments reveals that, unexpectedly, the VCA motifs of WASP, N-WASP, and WASH destabilize existing branches, as well as SPIN90-Arp2/3 at linear filament ends. Furthermore, branch stabilizer cortactin and destabilizer GMF each have a similar impact on SPIN90-activated Arp2/3. However, unlike branch junctions, SPIN90-Arp2/3 at the ends of linear filaments is not destabilized by piconewton forces and does not become less stable with time. It thus appears that linear and branched Arp2/3-generated filaments respond similarly to the regulatory proteins we have tested, albeit with some differences, but significantly differ in their responses to aging and mechanical stress. These kinetic differences likely reflect the small conformational differences recently reported between Arp2/3 in branch junctions and linear filaments and suggest that their turnover in cells may be differently regulated.

Effect of a single dose of intravenous ketamine on the wish to hasten death in palliative care: A case report in advanced cancer.

OBJECTIVES: The suffering experienced by some patients at the end of their lives can lead to a wish to hasten death (WTHD). It is sometimes an existential suffering, refractory to palliative care even if well conducted, which leads to this desire. Since several years, in psychiatry, the rapid anti-suicidal effects of a single injection of ketamine have been proven. WTHD and suicidal ideation have similarities. The injection of a single dose of ketamine could have an efficiency on the desire to hasten death. METHODS: We report the case of a woman with advanced breast cancer expressing a WTHD, treated by ketamine. RESULTS: A 78-year-old woman expressed a WTHD (request for euthanasia) because of existential suffering following a loss of autonomy related to cancer. The suicide item was 4 on the Montgomery-Åsberg Depression Rating Scale (MADRS). She had no associated pain or depression. A single dose of intravenous ketamine 1 mg/kg over 40 min plus 1 mg of midazolam was injected. She had no adverse effects. From D1 post-injection to D3, the WTHD disappeared completely with a MADRS suicide item at 0. At D5, the WTHD started to reappear, and at D6, the previous speech was completely back. SIGNIFICANCE OF THE RESULTS: These results suggest an effect of ketamine on WTHD. This opens up the possibility of treating existential suffering at the end of life. The optimal dosage of this treatment would have to be determined as well as a maintenance of efficacy scheme.

Text4Hope Effectiveness in Reducing Psychological Symptoms among Young Adults in Canada: Longitudinal and Naturalistic Controlled Program Evaluation.

BACKGROUND: Chronic stress, anxiety, and depression are psychological problems that can hurt young adults, interfering with their everyday function, academic achievement, and interpersonal relationships. This study aimed to assess the impact of Text4Hope, an online mental health service, on the psychological well-being of young adults. METHODS: This study adopted both longitudinal and naturalistic controlled trial designs. It examined clinical outcomes in young adult (≤26 years old) subscribers of Text4Hope who completed surveys at baseline and six weeks and compared clinical parameters in two groups of subscribers. The first group comprised the intervention group (IG) (young adult subscribers who received once-daily supportive text messages for six weeks and completed sixth-week evaluation measures between 26 April and 12 July 2020), and the second group was the control group (CG) (young adult subscribers who joined Text4Hope in the same time frame and completed a baseline survey and were yet to receive any text messages). The prevalence of moderate to high stress, anxiety, and depression was measured at baseline and six weeks in the longitudinal study and between the two groups for the naturalistic controlled study using the Perceived Stress Scale (PSS-10), Generalized Anxiety Disorder 7-item (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Inferential statistics, including the t-test, McNemar test, chi-square, and binary logistic regression analyses, were used to evaluate the differences in the prevalence and severity of the psychological symptoms. RESULTS: In the longitudinal study, of the 9214 subscribers to Text4Hope who completed the baseline survey, 1047 (11.4%) were identified as youth. For the young adult subscribers who completed both the baseline and sixth-week surveys (n = 114), a significant reduction in the prevalence of moderate to high stress (8%) and likely GAD (20%) from baseline to six weeks was reported. Similarly, there was a significant reduction in the mean scores on the PSS-10, GAD-7, and Composite Mental Health score but not the PHQ-9 from baseline to six weeks. The largest reduction in mean scores was for the GAD-7 scale (18.4%), with a small effect size overall. For the naturalistic study, the IG included 173 young adult subscribers of Text4Hope who completed the sixth-week survey compared to 92 subscribers in the CG who completed the baseline survey during the designated period. There was a significantly lower prevalence for likely Moderate Depressive Disorder (MDD) (25.2%) and suicidal thoughts/thoughts of self-harm (48.4%), with a small effect size in the IG compared to the CG. Similarly, lower mean scores were reported for all outcome variables in the IG compared to the CG, with a small to medium effect size. The receipt of daily supportive text messages for six weeks resulted in significantly lower odds of both likely GAD and experiencing thoughts of self-harm or death wish while controlling for sociodemographic characteristics. CONCLUSIONS: The Text4Hope service is an effective tool for mental health support for young adult subscribers. Young adults receiving the service exhibited a reduction in psychological symptoms, including thoughts of self-harm or death wish. This population-level intervention program can be used to effectively support young adult mental health and in suicide prevention programs.