The Psychoneuroimmunological Model of Moral Distress and Health in Healthcare Workers: Toward Individual and System-Level Solutions.

Healthcare is presently experiencing a global workforce crisis, marked by the inability of hospitals to retain qualified healthcare workers. Indeed, poor working conditions and staff shortages have contributed to structural collapse and placed a heavy toll on healthcare workers' (HCWs) well-being, with many suffering from stress, exhaustion, demoralization, and burnout. An additional factor driving qualified HCWs away is the repeated experience of moral distress, or the inability to act according to internally held moral values and perceived ethical obligations due to internal and external constraints. Despite general awareness of this crisis, we currently lack an organized understanding of how stress leads to poor health, wellbeing, and performance in healthcare workers. To address this critical issue, we first review the literature on moral distress, stress, and health in HCWs. Second, we summarize the biobehavioral pathways linking occupational and interpersonal stressors to health in this population, focusing on neuroendocrine, immune, genetic, and epigenetic processes. Third, we propose a novel Psychoneuroimmunological Model of Moral Distress and Health in HCWs based on this literature. Finally, we discuss evidence-based individual- and system-level interventions for preventing stress and promoting resilience at work. Throughout this review, we underscore that stress levels in HCWs are a major public health concern, and that a combination of system-level and individual-level interventions are necessary to address preventable health care harm and foster resilience in this population, including new health policies, mental health initiatives, and additional translational research.

Effects of dignity therapy on psychological distress and wellbeing of palliative care patients and family caregivers - a randomized controlled study.

BACKGROUND: This study extended the original Dignity Therapy (DT) intervention by including partners and family caregivers (FCs) of terminally-ill cancer patients with the overall aim of evaluating whether DT can mitigate distress in both patients nearing the end of life and their FCs. METHODS: In this multicenter, randomized controlled trial (RCT), a total of 68 patients with life expectancy < 6 months and clinically-relevant stress levels (Hospital Anxiety Depression total score; HADStot ≥ 8) including their FCs were randomly assigned to DT, DT + (including their FCs), or standard palliative care (SPC) in a 1:1:1 ratio. Study participants were asked to complete a set of questionnaires pre- and post-intervention. RESULTS: The coalesced group (DT and DT +) revealed a significant increase in patients' perceived quality of life (FACIT-Pal-14) following the intervention (mean difference 6.15, SD = 1.86, p < 0.01). We found a statistically significant group-by-time interaction effect: while the HADStot of patients in the intervention group remained stable over the pre-post period, the control group's HADStot increased (F = 4.33, df = 1, 82.9; p < 0.05), indicating a protective effect of DT. Most patients and their FCs found DT useful and would recommend it to other individuals in their situation. CONCLUSIONS: The DT intervention has been well-received and shows the potential to increase HRQoL and prevent further mental health deterioration, illness burden and suffering in terminally-ill patients. The DT intervention holds the potential to serve as a valuable tool for facilitating end-of-life conversations among terminally-ill patients and their FCs. However, the implementation of DT within the framework of a RCT in a palliative care setting poses significant challenges. We suggest a slightly modified and less resource-intensive version of DT that is to provide the DT inventory to FCs of terminally-ill patients, empowering them to ask the questions that matter most to them over their loved one's final days. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov -Protocol Record NCT02646527; date of registration: 04/01/2016). The CONSORT 2010 guidelines were used for properly reporting how the randomized trial was conducted.

Characteristics and clinical challenges in patients with substance use disorder in palliative care-experience from a tertiary center in a high-income country.

BACKGROUND: Access to palliative care is often limited for challenging and vulnerable groups, including persons with substance use disorders. However, with optimized healthcare options and liberal substitution policies, this patient group is likely to increase over the upcoming years, and comorbidities will also influence the need for palliative support. Here, we aim at analyzing characteristics and specific challenges associated with substance use disorders (SUD) in palliative care. METHODS: We retrospectively reviewed all patients diagnosed with substance use disorder that were treated at our Competence Center Palliative Care within the University Hospital Zurich, Switzerland between 2015 and 2021. Patient characteristics, including age, gender, duration of hospitalization, as well as specific metrics like body mass index, distinct palliative care assessment scores, and in-hospital opioid consumption were retrieved from the electronic patient files. Demographics and clinical data were analyzed by descriptive statistics, and compared to those of a control group of palliative care patients without SUD. An opioid calculator was used to standardize opioid intake based on morphine equivalents for meaningful comparisons. RESULTS: The primary characteristics revealed that the majority of individuals were single (56%), had no children (83%), lived alone (39%), and were either unemployed or recipients of a disability pension (in total 50%). Nicotine (89%), opioids (67%), and alcohol (67%) were the most used substances. We identified various comorbidities including psychiatric illnesses alongside SUD (56%), hepatitis A, B, or C (33%), and HIV infection (17%). Patients with SUD were significantly younger (p < 0.5), predominantly male (p < 0.05), and reported a higher prevalence of pain (p < 0.5) compared to the standard cohort of palliative patients. Regarding the challenges most frequently reported by healthcare practitioners, non-compliance, multimorbidity, challenging communication, biographical trauma, lack of social support, and unstable housing situations played a key role. CONCLUSION: Patients with SUD represent a complex and vulnerable group dealing with multiple comorbidities that profoundly affect both their physical and psychological well-being. Understanding their unique characteristics is pivotal in providing precise and suitable palliative care.

Socio-economic determinants for the place of last care: results from the acute palliative care unit of a large comprehensive cancer center in a high-income country in Europe.

BACKGROUND AND INTRODUCTION: The place of last care carries importance for patients at the end of life. It is influenced by the realities of the social welfare and healthcare systems, cultural aspects, and symptom burden. This study aims to investigate the place of care trajectories of patients admitted to an acute palliative care unit. MATERIALS AND METHODS: The medical records of all patients hospitalized on our acute palliative care unit in 2019 were assessed. Demographic, socio-economic and disease characteristics were recorded. Descriptive and inferential statistics were used to identify determinants for place of last care. RESULTS: A total of 377 patients were included in this study. Median age was 71 (IQR, 59-81) years. Of these patients, 56% (n = 210) were male. The majority of patients was Swiss (80%; n = 300); about 60% (n = 226) reported a Christian confession; and 77% had completed high school or tertiary education. Most patients (80%, n = 300) had a cancer diagnosis. The acute palliative care unit was the place of last care for 54% of patients. Gender, nationality, religion, health insurance, and highest level of completed education were no predictors for place of last care, yet previous outpatient palliative care involvement decreased the odds of dying in a hospital (OR, 0.301; 95% CI, 0.180-0.505; p-value < 0.001). CONCLUSION: More than half of patients admitted for end-of-life care died on the acute palliative care unit. While socio-economic factors did not determine place of last care, previous involvement of outpatient palliative care is a lever to facilitate dying at home.

[End-of-Life Dreams and Visions]. / Traum- und Wachvisionen am Lebensende.

End-of-Life Dreams and Visions Abstract: End-of life dreams and visions (ELDVs) or so-called death bed phenomena are transcendent experiences at the end of life that can be visual, auditory and/or kinesthetic, and often include visions of (deceased) loved ones, close friends or perceptions of places, travels, bright lights, or music. ELDVs typically occur weeks to hours prior to death and may comfort the dying and prepare spiritually for the end of life. Such experiences are frequently reported by dying individuals, the prevalence varying between 30 and 80%, but in the clinical context ELDVs are usually neglected, but interpreted and treated as pathological changes in the brain that result in, and from, delirium. This article tries to enlighten the occurrence, the contents and meanings of ELDVs in dying persons as opposed to delirium and night dreams using findings from the literature and from clinical observations. Implications of these conclusions for palliative care and the therapeutic relevance of ELDVs when taking care of dying individuals and their loved ones will also be discussed.

Validation and extension of the METSSS score in a metastatic cancer patient cohort after palliative radiotherapy within the last phase of life.

Introduction and background: Choosing the right treatment for the right patient in a setting of metastatic cancer disease remains a challenge. To facilitate clinical decision-making, predictive tools have been developed to personalize treatment. Here, we aim to assess the use of the recently proposed "METSSS score" as a prognostic tool for overall survival of cancer patients after palliative radiotherapy in the last phase of life. Methods: All patients treated with palliative radiotherapy at the end-of-life at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 were included in this study. Data on demographics, diagnosis, treatment and comorbidities was extracted from the treatment planning and the electronical medical records system. To statistically assess the validity of the "METSSS score", the mortality risk score was calculated, followed by stratification of all patients to prognostic risk groups. The prediction of the 1-year overall survival estimates was subsequently calculated. Results: Over the past decade, 274 patients have received palliative radiotherapy during the end-of-life period. One third of patients was female (34%, n = 93). The most frequent primary tumor was lung cancer (n = 121, 44%), and 55% of patients (n = 152) had no comorbidities according to the Charlson-Deyo comorbidity index. The most common radiotherapy site was the brain and eye region (42%, n = 115). The median actual overall survival of all patients was 40 days from the start of radiotherapy. The "METSSS score" survival model predicted that 269 patients (98.1%) belong into the high-risk, four patients (1.5%) into the medium-risk, and one patient (0.4%) into the low-risk group. The predicted median 1-year overall survival was 10%. Discussion: The METSSS score correctly predicted the survival of our end-of-life patient cohort by assigning them into the highest risk category, and it can therefore serve as a decision-making tool when assigning patient to symptomatic radiotherapy.

Prevalence and predictors for 72-h mortality after transfer to acute palliative care unit.

PURPOSE: Accurate prediction of survival is important to facilitate clinical decision-making and improve quality of care at the end of life. While it is well documented that survival prediction poses a challenge for treating physicians, the need for clinically valuable predictive factors has not been met. This study aims to quantify the prevalence of patient transfer 72 h before death onto the acute palliative care unit in a tertiary care center in Switzerland, and to identify factors predictive of 72-h mortality. METHODS: All patients hospitalized between January and December 2020 on the acute palliative care unit of the Competence Center Palliative Care of the Department of Radiation Oncology at the University Hospital Zurich were assessed. Variables were retrieved from the electronic medical records. Univariable and multivariable logistic regressions were used to identify predictors of mortality. RESULTS: A total of 398 patients were screened, of which 188 were assessed. Every fifth patient spent less than 72 h on the acute palliative care unit before death. In multivariable logistic regression analysis, predictors for 72-h mortality after transfer were no prior palliative care consult (p = 0.011), no advance care directive (p = 0.044), lower performance status (p = 0.035), lower self-care index (p = 0.003), and lower blood albumin level (p = 0.026). CONCLUSION: Late transfer to the acute palliative care unit is not uncommon, which can cause additional distress to patients and caretakers. Though clinically practical short-term survival predictors remain largely unidentified, early integration of palliative care should be practiced more regularly in patients with life-limiting illness.

Quality-of-life and toxicity in cancer patients treated with multiple courses of radiation therapy.

Background: Treatment of metastatic cancer patients with multiple repeat courses of radiotherapy has become more frequent due to their improved overall survival. However, very little is known about their long-term outcome. This analysis reports on the quality-of-life, hematologic toxicity, patient-reported experiences and satisfaction, and psychological distress of cancer patients treated with multiple repeat radiotherapy. Methods: All patients treated with ≥5 courses of radiotherapy between 2011 and 2019 at the Department of Radiation Oncology, University Hospital Zurich (USZ) were screened for this study. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. All patients completed two questionnaires: EORTC QLQ-C30 questionnaire for quality-of-life and a questionnaire evaluating psychological distress and patient-reported experiences. Hematologic toxicities were assessed via a recent blood sample. Results: Of n = 33 patients treated with ≥5 radiotherapy courses and being alive, 20 (60.6%) participated in this study. The most common primary tumor was non-small cell lung cancer (n = 14, 42.4%). The most common sites of irradiation were brain (n = 78, 37.1%) and bone metastases (n = 59, 28.1%). All participating patients reported that they had experienced a subjective benefit from multiple repeat radiotherapy and denied increased side effects in later radiotherapy courses. Yet, 45% (n = 9) of the patients reported an increase of psychological distress with increasing numbers of radiotherapy treatments. While global health status was stable, patients having received multiple repeat radiotherapy reported increased fatigue (p = <0.006). Blood analysis showed significantly reduced hemoglobin and lymphocyte levels compared to the healthy population (p = <0.03). Discussion and conclusion: Patient-reported experiences and satisfaction of long-term cancer patients treated with multiple repeat radiotherapy are positive. However, increased levels of fatigue and significantly reduced hemoglobin and lymphocyte levels were observed. These data indicate the need to further investigate the effects of multiple courses of radiotherapy in chronic cancer patients.

Discharge Destinations of Delirious Patients: Findings From a Prospective Cohort Study of 27,026 Patients From a Large Health Care System.

OBJECTIVES: Delirium is known to contribute to increased rates of institutionalization and mortality. The full extent of adverse outcomes, however, remains understudied. We aimed to systematically assess the discharge destinations and mortality risk in delirious patients in a large sample across all hospital services. DESIGN: Pragmatic prospective cohort study of consecutive admissions to a large health care system. SETTING AND PARTICIPANTS: A total of 27,026 consecutive adults (>18 years old) with length of stay of at least 24 hours in a tertiary care center from January 1 to December 31, 2014. METHODS: Presence of delirium determined by routine delirium screening. Clinical characteristics, discharge destination, and mortality were collected. Calculation of odds ratios (ORs) with logistic regression with adjustment for age, sex, and Charlson comorbidity index (CCI). RESULTS: Delirium was detected in 19.7% of patients (5313 of 27,026), median age of delirious patients was 56 years (25-75 interquartile range = 37-70). The electronic health record (DSM-5-based) delirium algorithm correctly identified 93.3% of delirium diagnoses made by consultation-liaison psychiatrists. Across services, the odds of delirious patients returning home was significantly reduced [OR 0.12; confidence interval (CI) 0.10-0.13; P < .001]. Rather, these patients were transferred to acute rehabilitation (OR 4.15; CI 3.78-4.55; P < .001) or nursing homes (OR 4.12; CI 3.45-4.93; P < .001). Delirious patients had a significantly increased adjusted mortality risk (OR 30.0; CI 23.2-39.4; P < .001). CONCLUSIONS AND IMPLICATIONS: This study advances our understanding of the discharge destination across all services in adults admitted to a large hospital system. Delirium was associated with reduced odds of returning home, increased odds of discharge to a setting of higher dependency, and excess mortality independent of comorbidity, age, and sex. These findings emphasize the potentially devastating outcomes associated with delirium and highlight the need for timely diagnosis and hospital-wide management.

[Delirium Management in Palliative Care]. / Delirmanagement in der Palliative Care.

Delirium Management in Palliative Care Abstract. Delirium is one of the most common neuropsychiatric complications in patients with advanced incurable disease. End-of-life delirium is common but is often overlooked, undiagnosed or incorrectly diagnosed/untreated. Delirium should also be treated in a palliative situation - as far as possible - because persistent delirious states increase the patient's fragility, limit physical functionality and shorten the lifespan. In addition, acute states of confusion trigger high levels of distress in affected patients and their relatives, impair the quality of life and a dignified dying process. While hallucinations and visions at the end of life are interpreted as delirium in medicine and treated as such, this phenomenon is interpreted by philosophical and theological hermeneutics as a resource that can help patients and their relatives to reconcile with past life events and to deal with the process of dying. However, the occurrence of end-of-life visions as opposed to delirium has not yet been studied very much and requires more detailed exploration.

Continuity and coordination of care in highly selected chronic cancer patients treated with multiple repeat radiation therapy.

INTRODUCTION AND BACKGROUND: As cancer is developing into a chronic disease due to longer survival, continuity and coordination of oncological care are becoming more important for patients. As radiation oncology departments are an integral part of cancer care and as repeat irradiation becomes more commonplace, the relevance of continuity and coordination of care in operating procedures is increasing. This study aims to perform a single-institution analysis of cancer patients in which continuity and coordination of care matters most, namely the highly selected group with multiple repeat course radiotherapy throughout their chronic disease. MATERIALS AND METHODS: All patients who received at least five courses of radiotherapy at the Department of Radiation Oncology at the University Hospital Zurich from 2011 to 2019 and who were alive at the time of the initiation of this project were included into this study. Patient and treatment characteristics were extracted from the hospital information and treatment planning systems. All patients completed two questionnaires on continuity of care, one of which was designed in-house and one of which was taken from the literature. RESULTS: Of the 33 patients identified at baseline, 20 (60.6%) participated in this study. A median of 6 years (range 3-13) elapsed between the first and the last visit at the cancer center. The median number of involved primary oncologists at the radiation oncology department was two (range 1-5). Fifty-seven percent of radiation therapy courses were preceded by a tumor board discussion. Both questionnaires showed high levels of experienced continuity of care. No statistically significant differences in experienced continuity of care between groups with more or less than two primary oncologists was found. DISCUSSION AND CONCLUSION: Patients treated with multiple repeat radiation therapy at our department over the past decade experienced high levels of continuity of care, yet further efforts should be undertaken to coordinate care among oncological disciplines in large cancer centers through better and increased use of interdisciplinary tumor boards.

Single-institution analysis of the prevalence, indications and outcomes of end-of-life radiotherapy.

BACKGROUND: Radiotherapy plays an important role for symptom control in advanced stage cancer patients. Yet patients need to be carefully selected, and its use and benefits must be weighed against time spent under treatment and patient priorities in the last phase of life. In this study, we assess prevalence, indications and outcomes of radiotherapy close to death. METHODS: We screened all radiotherapy treatments performed at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 to identify those which occurred near patients' end-of-life. Analyzed data was extracted from the database of the Comprehensive Cancer Center Zurich, the treatment planning system Aria® and the electronical medical records system KISIM®. RESULTS: Within 60 days of death, 377 radiotherapy courses were prescribed to 280 patients, which constitutes 3.4% of all radiotherapy courses administered over the last decade at our department. Within 60-31, 30-8, and 7-0 days to death 164, 159, and 54 radiotherapy courses were prescribed, respectively. The most frequent treatment sites were brain (N = 122, 32%) and bone (N = 119, 32%), and there was no statistically significant difference in treatment site between the three sub-groups. The most common regimen was 10x3Gy (N = 130, 35%) in all three sub-groups (p = 0.23). Radiotherapy finished more than one week before death was associated with high completion rates (>80%) and treatment benefit (>55%). CONCLUSION: Patient selection and survival prognostication remains challenging for radiation oncologists. While radiotherapy achieved high completion and success rates until one week before death, treatment within one week of death should be restricted to carefully selected patients or avoided altogether.

The Actualization of the Transplantation Complex on the Axis of Psychosomatic Totality-Results of a Qualitative Study.

Although transplantation medicine is not new, there is a clinically justified gap in the existing literature with respect to the psychological processing of lung transplants. The present study aims to examine whether lung transplantation leads to an actualization of psychological, e.g., oral-sadistic fantasies. Following a qualitative approach, 38 lung transplant patients were interviewed three times within the first six months after transplantation. Data analysis focused on identifying unconscious and conscious material. The inter-rater reliability for all codes was calculated using Krippendorff's Alpha (c-α-binary = 0.94). Direct and implicit evidence of a so-called transplantation complex was detected e.g., regarding the "incorporation" of the dead donor and his lungs. These processes occur predominantly at an imaginary level and are related to the body. Our findings emphasize that such psychological aspects should be borne in mind in the psychological treatment of lung-transplant patients in order to improve the processing of lung transplants, and that this might have a positive effect on patient adherence.

Delirium is associated with an increased morbidity and in-hospital mortality in cancer patients: Results from a prospective cohort study.

OBJECTIVE: Delirium is a frequent complication in advanced cancer patients, among whom it is frequently underdiagnosed and inadequately treated. To date, evidence on risk factors and the prognostic impact of delirium on outcomes remains sparse in this patient population. METHOD: In this prospective observational cohort study at a single tertiary-care center, 1,350 cancer patients were enrolled. Simple and multiple logistic regression models were utilized to identify associations between predisposing and precipitating factors and delirium. Cox proportional-hazards models were used to estimate the effect of delirium on death rate. RESULTS: In our patient cohort, the prevalence of delirium was 34.3%. Delirium was associated inter alia with prolonged hospitalization, a doubling of care requirements, increased healthcare costs, increased need for institutionalization (OR 3.22), and increased mortality (OR 8.78). Predisposing factors for delirium were impaired activity (OR 10.82), frailty (OR 4.75); hearing (OR 2.23) and visual impairment (OR 1.89), chronic pneumonitis (OR 2.62), hypertension (OR 1.46), and renal insufficiency (OR 1.82). Precipitating factors were acute renal failure (OR 7.50), pressure sores (OR 3.78), pain (OR 2.86), and cystitis (OR 1.32). On multivariate Cox regression, delirium increased the mortality risk sixfold (HR 5.66). Age ≥ 65 years and comorbidities further doubled the mortality risk of delirious patients (HR 1.77; HR 2.05). SIGNIFICANCE OF RESULTS: Delirium is common in cancer patients and associated with increased morbidity and mortality. Systematically categorizing predisposing and precipitating factors might yield new strategies for preventing and managing delirium in cancer patients.

Death in delirious palliative-care patients occurs irrespective of age: A prospective, observational cohort study of 229 delirious palliative-care patients.

OBJECTIVES: Patients with terminal illness are at high risk of developing delirium, in particular, those with multiple predisposing and precipitating risk factors. Delirium in palliative care is largely under-researched, and few studies have systematically assessed key aspects of delirium in elderly, palliative-care patients. METHODS: In this prospective, observational cohort study at a tertiary care center, 229 delirious palliative-care patients stratified by age: <65 (N = 105) and ≥65 years (N = 124), were analyzed with logistic regression models to identify associations with respect to predisposing and precipitating factors. RESULTS: In 88% of the patients, the underlying diagnosis was cancer. Mortality rate and median time to death did not differ significantly between the two age groups. No inter-group differences were detected with respect to gender, care requirements, length of hospital stay, or medical costs. In patients ≥65 years, exclusively predisposing factors were relevant for delirium, including hearing impairment [odds ratio (OR) 3.64; confidence interval (CI) 1.90-6.99; P < 0.001], hypertension (OR 3.57; CI 1.84-6.92; P < 0.001), and chronic kidney disease (OR 4.84; CI 1.19-19.72; P = 0.028). In contrast, in patients <65 years, only precipitating factors were relevant for delirium, including cerebral edema (OR 0.02; CI 0.01-0.43; P = 0.012). SIGNIFICANCE OF RESULTS: The results of this study demonstrate that death in delirious palliative-care patients occurs irrespective of age. The multifactorial nature and adverse outcomes of delirium across all age in these patients require clinical recognition. Potentially reversible factors should be detected early to prevent or mitigate delirium and its poor survival outcomes.

The prevalence rates and sequelae of delirium at age older than 90 years.

OBJECTIVE: Although age and pre-existent dementia are robust risk factors for developing delirium, evidence for patients older than 90 years is lacking. Therefore, this study assesses the delirium prevalence rates and sequelae in this age group. METHOD: Based on a Diagnostic and Statistical Manual (DSM)-5, Delirium Observation screening scale (DOS), and Intensive Care Delirium Screening Checklist (ICDSC) construct, in this prospective cohort study, the prevalence rates and sequelae of delirium were determined in 428 patients older than 90 years by simple logistic regressions and corresponding odds ratios (ORs). RESULTS: The overall prevalence delirium rate was 45.2%, with a wide range depending upon specialty: intermediate and intensive care services (83.1%), plastic surgery and palliative care (75%), neurology (72%), internal medicine (69%) vs. dermatology (26.5%), and angiology (14.5%). Delirium occurred irrespective of age and gender; however, pre-existent dementia was the strongest delirium predictor (OR 36.05). Delirious patients were less commonly admitted from home (OR 0.47) than from assisted living (OR 2.24), indicating functional impairment. These patients were more severely ill, as indicated by emergency (OR 3.25) vs. elective admission (OR 0.3), requirement for intensive care management (OR 2.12) and ventilation (OR 5.56-8.33). At discharge, one-third did not return home (OR 0.22) and almost half were transferred to assisted living (OR 2.63), or deceased (OR 47.76). SIGNIFICANCE OF RESULTS: At age older than 90 years, the prevalence and sequelae of delirium are substantial. In particular, functional impairment and pre-existent dementia predicted delirium and subsequently, the loss of independence and death were imminent.

The Psychobiology of Bereavement and Health: A Conceptual Review From the Perspective of Social Signal Transduction Theory of Depression.

Losing a spouse is considered one of the most stressful life events a person can experience. Particularly in the immediate weeks and months after the loss, bereavement is associated with a significantly increased risk of morbidity and mortality. Despite an abundance of research aimed at identifying risk factors for adverse health outcomes following marital death, the mechanisms through which mental and physical health problems emerge following bereavement remain poorly understood. To address this issue, the present review examines several pathways that may link bereavement and health, including inflammation and immune dysregulation, genetic and epigenetic changes, gut microbiota activity, and biological aging. We then describe how these processes may be viewed from the perspective of the Social Signal Transduction Theory of Depression to provide a novel framework for understanding individual differences in long-term trajectories of adjustment to interpersonal loss. Finally, we discuss several avenues for future research on psychobiological mechanisms linking bereavement with mental and physical health outcomes.

Sex-specific and gender-specific aspects in patient-reported outcomes.

Patient-reported outcomes (PROs) are important tools in patient-centred medicine and allow for individual assessment of symptom burden and aspects of patients' quality of life. While sex and gender differences have emerged in preclinical and clinical medicine, these differences are not adequately represented in the development and use of patient-reported outcome measures. However, even in personalised approaches, undesirable biases may occur when samples are unbalanced for certain characteristics, such as sex or gender. This review summarises the current status of the literature and trends in PROs with a focus on sex and gender aspects.