Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates.

INTRODUCTION: Tau aggregation into paired helical filaments and neurofibrillary tangles is characteristic of Alzheimer's disease (AD) and related disorders. However, biochemical assays for the quantification of soluble, earlier-stage tau aggregates are lacking. We describe an immunoassay that is selective for tau oligomers and related soluble aggregates over monomers. METHODS: A homogeneous (single-antibody) immunoassay was developed using a novel anti-tau monoclonal antibody and validated with recombinant and brain tissue-derived tau. RESULTS: The assay signals were concentration dependent for recombinant tau aggregates in solution but not monomers, and recognized peptides within, but not outside, the aggregation-prone microtubule binding region. The signals in inferior and middle frontal cortical tissue homogenates increased with neuropathologically determined Braak staging, and were higher in insoluble than soluble homogenized brain fractions. Autopsy-verified AD gave stronger signals than other neurodegenerative diseases. DISCUSSION: The quantitative oligomer/soluble aggregate-specific assay can identify soluble tau aggregates, including oligomers, from monomers in human and in vitro biospecimens. HIGHLIGHTS: The aggregation of tau to form fibrils and neurofibrillary tangles is a key feature of Alzheimer's disease. However, biochemical assays for the quantification of oligomers/soluble aggregated forms of tau are lacking. We developed a new assay that preferentially binds to soluble tau aggregates, including oligomers and fibrils, versus monomers. The assay signal increased corresponding to the total protein content, Braak staging, and insolubility of the sequentially homogenized brain tissue fractions in an autopsy-verified cohort. The assay recognized tau peptides containing the microtubule binding region but not those covering the N- or C-terminal regions only.

Two Years with COVID-19: The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study.

INTRODUCTION: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. OBJECTIVES: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. METHODS: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. RESULTS: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (ß-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). CONCLUSION: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.

Phonology in Swedish-speaking 3-year-olds born with cleft lip and palate and the relationship with consonant production at 18 months.

BACKGROUND: Approximately 50% of children born with cleft palate present speech difficulties around 3 years of age, and several studies report on persisting phonological problems after palatal closure. However, studies on early phonology related to cleft palate are few and have so far mainly been carried out on English-speaking children. Studies on phonology related to cleft palate in languages other than English are also warranted. AIMS: To assess phonology in Swedish-speaking children born with and without unilateral cleft lip and palate (UCLP) at 3 years of age, and to identify variables at 18 months that are associated with restricted phonology at age 3 years. METHODS & PROCEDURES: Eighteen consecutive children born with UCLP and 20 children without cleft lip and palate were included. Transcriptions of audio recordings at 18 months and 3 years were used. Per cent correct consonants adjusted for age (PCC-A), the number of established phonemes, and phonological simplification processes at 3 years were assessed and compared with different aspects of consonant inventory at 18 months. OUTCOMES & RESULTS: PCC-A, the number of established phonemes, and the total number of phonological processes differed significantly at 3 years between the two groups. Total number of oral consonants, oral stops, dental/alveolar oral stops and number of different oral stops at 18 months correlated significantly with PCC-A at 3 years in the UCLP group. CONCLUSIONS & IMPLICATIONS: As a group, children born with UCLP displayed deviant phonology at 3 years compared with peers without cleft lip and palate. Measures of oral consonant and stop production at 18 months might be possible predictors for phonology at 3 years in children born with cleft palate.

Charting Health Challenges for Digital Preventive Interventions Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: National Long-Term Follow-Up Survey of Self-Rated Health Outcomes.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, but the prognosis has remarkably improved over the last 50 years in high-income countries, and thus, there is a focus on long-term health outcomes following survival and how to best provide health care support to adult long-term survivors of childhood ALL to prevent and handle potential health problems. Digital health interventions are promising to deliver feasible health promotion and prevention programs. This is particularly relevant for ensuring long-term follow-up in cases where continuous contact with oncology care may be disrupted. Moreover, these interventions are beneficial in reaching geographically dispersed target groups and overcoming the time constraints of everyday life that often hinder participation in such programs. OBJECTIVE: This study aimed to fill the gaps in existing research on adult long-term survivors of childhood ALL and provide formative data that can inform the development of formalized follow-up services designed to meet the needs of these survivors in ways that align with their preferences for digital health interventions. METHODS: In this cross-sectional national study, adult survivors (aged ≥18 years) of childhood ALL for over 10 years after diagnosis were compared to their siblings in terms of mental and physical health-related factors, including sleep, stress, anxiety, and depression (Depression Anxiety and Stress Scale 21 [DASS-21]); several dimensions of fatigue (Multidimensional Fatigue Inventory 20 [MFI-20]); work ability (Work Ability Index); chronic pain; and prevalences of diabetes, cardiovascular disease, headache or migraine, and rheumatic disease. RESULTS: Overall, 426 of 855 eligible ALL survivors responded (mean age 30.9, SD 7.7 years), and they participated at an average of 24 (SD 6.9) years after ALL diagnosis. Siblings (n=135; mean age 31.5, SD 7.7 years) acted as controls. Sleep quality, sleep quantity, and mean work ability scores were significantly lower, and physical fatigue, reduced motivation, and reduced activity scores were higher in ALL survivors than in siblings. There were no significant differences between the groups in terms of BMI and prevalence of chronic pain, depression, anxiety, or stress. Physical and psychological complications were more frequent among adult ALL survivors who had received hematopoietic stem cell transplantation (HSCT) than among those who had not received HSCT. CONCLUSIONS: Our nationwide cross-sectional study addressed the scarcity of knowledge regarding the self-reported health outcomes of adult long-term survivors of childhood ALL. We highlighted significant disparities within this population and emphasized the potential of comprehensive digital interventions that target vitality, sleep quality, fatigue, and psychosocial well-being to enhance well-being and bolster the capacity for managing chronic health conditions in this target group. Such an intervention would align with the needs of this target group, which is a prerequisite for successfully incorporating technology into the daily lives of survivors of childhood ALL.

Co-creation of a digital platform for peer support in a community of adolescent and young adult patients during and after cancer.

PURPOSE: Adolescents and young adults (AYAs) diagnosed with cancer report psychological challenges and social isolation. Peer support has been shown to be a valuable resource for coping with these experiences. The aim of this study was through co-creation map the needs for peer support among AYA cancer patients in Sweden; and building on these results to develop and test a prototype of a digital tool for peer support. METHOD: The study was conducted in co-creation in a team consisting of AYA cancer patients, researchers, and a health tech company in Sweden. Through interviews the needs for emotional support were investigated. Based on this information, a prototype of a digital platform for peer support was co-created by the team. The platform was tested and evaluated through an online survey and follow-up interviews as part of the development process. RESULTS: AYAs expressed feelings of loneliness and a desire to process their cancer experiences with peers. A prerequisite for a digital platform for peer support was the assurance of a high degree of security. Piloting the prototype, 87% reported feeling secure, all participants found it valuable to interact with peers on the platform. In the follow-up interviews, AYAs emphasizing the need to simplify this process while maintaining stringent security measures. CONCLUSION: Co-creating tools for support together with AYAs ensures relevance and usability. A secure digital platform for peer support represents a complement to other existing forms of support. The presence of moderators was found to enhance security. Further development of the platform's log-in procedure is necessary.

Adult survivors' perceptions of their childhood and the influences of being treated for acute lymphoblastic leukaemia with allogeneic hematopoietic stem cell transplantation as a child: A phenomenographic study.

PURPOSE: Adults who had acute lymphoblastic leukaemia (ALL) as children and were treated with allogeneic hematopoietic stem cell transplantation (aHSCT) may have been affected in their lives due to several long-term complications. From a clinical point of view, it is of interest to study how survivors describe their perceptions of their childhood today. The aim was therefore to describe how adults perceived their childhood and the influences of being treated for ALL with aHSCT as a child. METHOD: Semi-structured telephone interviews were undertaken with 18 adults who had been treated for childhood ALL with aHSCT and were included in a national cohort of childhood ALL survivors, diagnosed between 1985 and 2007 at an age between 0 and 17 years. A phenomenographic analysis was used. RESULTS: Three categories emerged: Feeling different, Feeling security and Feeling guilty. The informants felt that they had been different from other children but had felt security with the healthcare professionals and in care. They felt guilty because both their siblings' and parents' lives had been affected, but at the same time many perceived that they and their family members had become closer to one another. CONCLUSIONS: The results emphasised that adults who had been treated for childhood ALL with aHSCT were affected both in negative and positive ways during their childhood. This indicates the importance for early psychosocial care interventions directed to children during their treatment, but also the need for person-centred psychological care in long-term outpatient clinics.

A thematic analysis of how men and women post 56 years, unwind from work during their free time.

BACKGROUND: Recent research indicates that as men age, their tendency to ruminate about work decreases, while ruminating remains high in women, which poses an increased risk for impaired health among older women. OBJECTIVE: This study explored gender differences/similarities in the process of unwinding from work in men and women aged between 56-65 years. METHODS: Semi-structured qualitative interviews were conducted online with eight men and eight women, recruited from a UK leading organization that provides health care solutions between May and June 2022. Participants were asked about their job role and responsibilities, their leisure time activities, how they unwind post work, and their experiences of thinking about work related thoughts outside of work. Transcripts were analyzed using an inductive analysis. RESULTS: Three superordinate themes were identified that underpinned their ability to unwind: 'Work style', 'Creating work-life balance' and 'Switching off from one's responsibilities'. Women reported a more perfectionist approach, they set high standards for themselves, were worried about making mistakes, and demonstrated, if in a supervisory role, a more nurturing and holistic approach to their colleagues/subordinates, while men, were more focused on task completion. Most women, but not men, also described difficulties in psychologically switching off from work, and stated they could only truly relax outside the home, when they are away from household activities. CONCLUSION: The study provides nuanced insights into the experiences of unwinding from work, and the findings suggest the need for person-centric approaches in developing interventions to help workers over 56 years to psychologically disengage from work.

Tau protein profiling in tauopathies: a human brain study.

Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature of several neurodegenerative diseases called tauopathies, including Alzheimer's disease (AD). In AD, this pathological change is reflected by highly specific cerebrospinal fluid (CSF) tau biomarkers, including both phosphorylated and non-phosphorylated variants. Interestingly, despite tau pathology being at the core of all tauopathies, CSF tau biomarkers remain unchanged in certain tauopathies, e.g., progressive supranuclear palsy (PSP), Pick's disease (PiD), and corticobasal neurodegeneration (CBD). To better understand commonalities and differences between tauopathies, we report a multiplex assay combining immunoprecipitation and high-resolution mass spectrometry capable of detecting and quantifying peptides from different tau protein isoforms as well as non-phosphorylated and phosphorylated peptides, including those carrying multiple phosphorylations. We investigated the tau proteoforms in soluble and insoluble fractions of brain tissue from subjects with autopsy-confirmed tauopathies, including sporadic AD (n = 10), PSP (n = 11), PiD (n = 10), and CBD (n = 10), and controls (n = 10). Our results demonstrate that non-phosphorylated tau profiles differ across tauopathies, generally showing high abundance of microtubule-binding region (MTBR)-containing peptides in insoluble protein fractions compared with controls; the AD group showed 12-72 times higher levels of MTBR-containing aggregates. Quantification of tau isoforms showed the 3R being more abundant in PiD and the 4R isoform being more abundant in CBD and PSP in the insoluble fraction. Twenty-three different phosphorylated peptides were quantified. Most phosphorylated peptides were measurable in all investigated tauopathies. All phosphorylated peptides were significantly increased in AD insoluble fraction. However, doubly and triply phosphorylated peptides were significantly increased in AD even in the soluble fraction. Results were replicated using a validation cohort comprising AD (n = 10), CBD (n = 10), and controls (n = 10). Our study demonstrates that abnormal levels of phosphorylation and aggregation do indeed occur in non-AD tauopathies, however, both appear pronouncedly increased in AD, becoming a distinctive characteristic of AD pathology.

Did Descriptive and Prescriptive Norms About Gender Equality at Home Change During the COVID-19 Pandemic? A Cross-National Investigation.

Using data from 15 countries, this article investigates whether descriptive and prescriptive gender norms concerning housework and child care (domestic work) changed after the onset of the COVID-19 pandemic. Results of a total of 8,343 participants (M = 19.95, SD = 1.68) from two comparable student samples suggest that descriptive norms about unpaid domestic work have been affected by the pandemic, with individuals seeing mothers' relative to fathers' share of housework and child care as even larger. Moderation analyses revealed that the effect of the pandemic on descriptive norms about child care decreased with countries' increasing levels of gender equality; countries with stronger gender inequality showed a larger difference between pre- and post-pandemic. This study documents a shift in descriptive norms and discusses implications for gender equality-emphasizing the importance of addressing the additional challenges that mothers face during health-related crises.

Nurses' Perceptions of the Impact of a National Educational Program in Pediatric Oncology Nursing: A Cross-Sectional Evaluation.

Background: Specific knowledge is required in pediatric oncology, and specialization of nurses has been identified as a priority. In Sweden, a national program in pediatric oncology nursing has been offered since 2003. The aim of this study was to gain knowledge of nurses' perceptions of the impact of this educational program. Methods: Eighty nurses who had completed the educational program in three cohorts (2012-2019) were invited to participate in this cross-sectional survey. An electronic study-specific questionnaire containing multiple-choice questions was used. Data were analyzed using descriptive statistics and correlation tests. Results: Fifty-nine (74%) nurses completed the survey, of whom 98% responded that they would recommend the program to a large/fairly large extent. At the time of the survey, 15 (25%) participants had left pediatric oncology care. Among the remaining 44, 31 (71%) of the nurses were working bedside, and 13 (42%) of these combined this with a special position (e.g., consultant nurse). The education resulted in career advancement, as the number of nurses with special positions increased following completion of the program, from 20% to 59%. The vast majority stated that the knowledge gained from the education contributed to increased confidence in interactions with the children/families. Discussion: Continuing education of nurses in pediatric oncology has an impact on career opportunities in clinical practice and contributes to nurses' confidence and professional work. However, education is not enough to retain competent nurses. Employers need to be aware of the role of the work environment, aspects of work-life balance and career paths.

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations.

Alzheimer's disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input-output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.

Temporal trends in hospitalizations and 30-day mortality in older patients during the COVID pandemic from March 2020 to July 2021.

BACKGROUND: A reduction in mortality risk of COVID-19 throughout the first wave of the pandemic has been reported, but less is known about later waves. This study aimed to describe changes in hospitalizations and mortality of patients receiving inpatient geriatric care for COVID-19 or other causes during the pandemic. METHODS: Patients 70 years and older hospitalized in geriatric hospitals in Stockholm for COVID-19 or other causes between March 2020-July 2021 were included. Data on the incidence of COVID-positive cases and 30-day mortality of the total ≥ 70-year-old population, in relation to weekly hospitalizations and mortality after hospital admissions were analyzed. Findings The total number of hospitalizations was 5,320 for COVID-19 and 32,243 for non-COVID-cases. In COVID-patients, the 30-day mortality rate was highest at the beginning of the first wave (29% in March-April 2020), reached 17% at the second wave peak (November-December) followed by 11-13% in the third wave (March-July 2021). The mortality in non-COVID geriatric patients showed a similar trend, but of lower magnitude (5-10%). During the incidence peaks, COVID-19 hospitalizations displaced non-COVID geriatric patients. INTERPRETATION: Hospital admissions and 30-day mortality after hospitalizations for COVID-19 increased in periods of high community transmission, albeit with decreasing mortality rates from wave 1 to 3, with a probable vaccination effect in wave 3. Thus, the healthcare system could not compensate for the high community spread of COVID-19 during the pandemic peaks, which also led to displacing care for non-COVID geriatric patients.

Amyloid-ß metabolism in Niemann-Pick C disease models and patients.

Niemann-Pick type C (NPC) is a progressive neurodegenerative lysosomal disease with altered cellular lipid trafficking. The metabolism of amyloid-ß (Aß) - previously mainly studied in Alzheimer's disease - has been suggested to be altered in NPC. Here we aimed to perform a detailed characterization of metabolic products from the amyloid precursor protein (APP) in NPC models and patients. We used multiple analytical technologies, including immunoassays and immunoprecipitation followed by mass spectrometry (IP-MS) to characterize Aß peptides and soluble APP fragments (sAPP-α/ß) in cell media from pharmacologically (U18666A) and genetically (NPC1 ( -/- ) ) induced NPC cell models, and cerebrospinal fluid (CSF) from NPC cats and human patients. The pattern of Aß peptides and sAPP-α/ß fragments in cell media was differently affected by NPC-phenotype induced by U18666A treatment and by NPC1 ( -/- ) genotype. U18666A treatment increased the secreted media levels of sAPP-α, AßX-40 and AßX-42 and reduced the levels of sAPP-ß, Aß1-40 and Aß1-42, while IP-MS showed increased relative levels of Aß5-38 and Aß5-40 in response to treatment. NPC1 ( -/- ) cells had reduced media levels of sAPP-α and Aß1-16, and increased levels of sAPP-ß. NPC cats had altered CSF distribution of Aß peptides compared with normal cats. Cats treated with the potential disease-modifying compound 2-hydroxypropyl-ß-cyclodextrin had increased relative levels of short Aß peptides including Aß1-16 compared with untreated cats. NPC patients receiving ß-cyclodextrin had reduced levels over time of CSF Aß1-42, AßX-38, AßX-40, AßX-42 and sAPP-ß, as well as reduced levels of the axonal damage markers tau and phosphorylated tau. We conclude that NPC models have altered Aß metabolism, but with differences across experimental systems, suggesting that NPC1-loss of function, such as in NPC1 ( -/- ) cells, or NPC1-dysfunction, seen in NPC patients and cats as well as in U18666A-treated cells, may cause subtle but different effects on APP degradation pathways. The preliminary findings from NPC cats suggest that treatment with cyclodextrin may have an impact on APP processing pathways. CSF Aß, sAPP and tau biomarkers were dynamically altered over time in human NPC patients.

Visualizing the Invisible-The Needs and Wishes of Childhood Cancer Survivors for Digitally Mediated Emotional Peer Support.

This study aims to identify the needs and wishes of childhood cancer long-term survivors for digitally mediated emotional peer support. Survivors of childhood cancer (six men, seven women) aged 19-33, participated in semi-structured interviews (November-December 2020). Age of diagnosis ranged from 1 to 13 years. The interviews lasted between 45 and 85 min. A thematic analysis was used to identify three themes for needs: processing long-term complications of cancer treatment, processing psychosocial health and meeting others who share similar experiences; and another three themes reflecting wishes: digital tools for connecting with people who had had similar experiences, different modes of communication and a safe place with varying degrees of anonymity. The findings emphasized the needs and wishes of childhood cancer survivors to meet others who had had similar experiences using a digital tool that offered a secure place, with options for a variety of communication methods and levels of anonymity. Peer support can serve as an important complement to professional psychosocial support.

Health-related quality of life in adults treated for paediatric acute lymphoblastic leukaemia: a cross-sectional and longitudinal cohort study.

INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is the most common form of cancer in children. Although treatment methods have improved and resulted in significant improvement of survival and reduction in late effects and late mortality risk, the health-related quality of life (HRQOL) of survivors might be affected. To introduce new interventions in clinical practice with the potential to support positive HRQOL outcomes, more knowledge is needed on how HRQOL in this group is constructed and stimulated. The purpose of this study is to investigate how HRQOL is affected in adults treated for paediatric ALL, in a long-term perspective and possible factors influencing this relationship. METHODS AND ANALYSIS: This cohort of young adult ALL survivors allows for investigations of factors influencing HRQOL outcomes on a national level. Eligible participants are obtained from the Swedish Childhood Cancer quality registry. Data collection includes both a follow-up of data collected in 2012 (n=224) and recruitment of new eligible participants to the cohort (n=601). The cohort will cover survivors of paediatric ALL, diagnosed between 1985 and 2007, at an age between 0 and 15 years. Data will be collected using validated, multidimensional, self-administered instruments, designed to measure HRQOL (SF-36), social support, sense of coherence and resilience. ETHICS AND DISSEMINATION: The study will be carried out in accordance with the ethics permit obtained from the Swedish ethics review authority (Dnr 2019-05181). Dissemination of study results will take place through research articles and reports to the national patient organisation and the national network for consultancy nurses for this target group and to the working group for the Swedish national long-term care programme for childhood cancer. Results will also reach practical application within the follow-up clinic for adult childhood cancer survivors at Sahlgrenska Hospital in Gothenburg.

Development of an Electronic Frailty Index for Hospitalized Older Adults in Sweden.

BACKGROUND: Frailty assessment in the Swedish health system relies on the Clinical Frailty Scale (CFS), but it requires training, in-person evaluation, and is often missing in medical records. We aimed to develop an electronic frailty index (eFI) from routinely collected electronic health records (EHRs) and assess its association with adverse outcomes in hospitalized older adults. METHODS: EHRs were extracted for 18 225 patients with unplanned admissions between 1 March 2020 and 17 June 2021 from 9 geriatric clinics in Stockholm, Sweden. A 48-item eFI was constructed using diagnostic codes, functioning and other health indicators, and laboratory data. The CFS, Hospital Frailty Risk Score, and Charlson Comorbidity Index were used for comparative assessment of the eFI. We modeled in-hospital mortality and 30-day readmission using logistic regression; 30-day and 6-month mortality using Cox regression; and length of stay using linear regression. RESULTS: Thirteen thousand one hundred and eighty-eight patients were included in analyses (mean age 83.1 years). A 0.03 increment in the eFI was associated with higher risks of in-hospital (odds ratio: 1.65; 95% confidence interval: 1.54-1.78), 30-day (hazard ratio [HR]: 1.43; 1.38-1.48), and 6-month mortality (HR: 1.34; 1.31-1.37) adjusted for age and sex. Of the frailty and comorbidity measures, the eFI had the highest area under receiver operating characteristic curve for in-hospital mortality of 0.813. Higher eFI was associated with longer length of stay, but had a rather poor discrimination for 30-day readmission. CONCLUSIONS: An EHR-based eFI has robust associations with adverse outcomes, suggesting that it can be used in risk stratification in hospitalized older adults.

"A rewarding conclusion of the relationship": staff members' perspectives on providing bereavement follow-up.

GOALS OF WORK: Staff members in palliative home care play an important role in supporting bereaved family members. The aim of this study was to explore staff members' perspectives on providing such support. MATERIAL AND METHODS: Staff members in six units responded (n=120; response rate 58%) to a postal questionnaire with Likert-type and open-ended questions. The responses were analyzed using statistics and manifest content analysis. MAIN RESULTS: None of the respondents stated that bereavement follow-up was "most often difficult," 23% "most often rather difficult," 52.5% "most often rather easy," and 12.5% "most often easy." Apart from a tendency for age to be linked to perceived difficulty, there were no apparent patterns. Bereavement follow-up was a positive opportunity to support the family member's coping with their bereavement and to get feedback on the palliative care provided. Critical aspects concerned the question of whose needs actually were being met at bereavement follow-up, i.e., the staff members' needs for getting feedback on the care provided versus the risk of burdening the family members' by reminding them of the deceased's dying trajectory. Aspects that negatively influenced the staff members' experiences were complex and related, e.g., to the family member's dissatisfaction with the care provided, to the staff member's perceived lack of competence, and to the staff member's relationship to the family member. CONCLUSIONS: Bereavement follow-up was perceived as a rewarding conclusion to the relationship with the family member. The findings suggest that meaning-based coping might be an appropriate framework when understanding staff members' experiences with providing bereavement follow-up.

Early consonant production in Swedish infants with and without unilateral cleft lip and palate and two-stage palatal repair.

OBJECTIVE: To investigate consonant production at 12 and 18 months of age following early soft palate repair in infants with unilateral cleft lip and palate (UCLP), and to compare it with typically developing children without clefts. DESIGN: Randomized study with comparison group. PARTICIPANTS: Twenty Swedish infants born with UCLP and 21 without clefts (COMP) were included in a randomized trial of palatal surgery (Scandcleft project). Soft palate closure was completed at age 5 months; hard palate closure was performed in 11 of the infants with UCLP at 1 year of age (HPC) and was left open in nine (HPO). METHOD: Audio recordings at 12 months (UCLP  =  9, COMP  =  21) and at 18 months (UCLP  =  18, COMP  =  21) were phonetically transcribed. Consonant inventory, frequency of manner and place of articulation, true canonical babbling (TCB), and impact of hearing status were analyzed. RESULTS: At 12 months of age, all children had reached the stage of TCB. Mild hearing impairment was significantly correlated with fewer consonant types. A lower frequency of dentals and oral stops was found in the UCLP group than in the COMP group. However, the number of oral stops was high compared with what has been previously reported. CONCLUSIONS: Early soft palate closure seems to give a relatively high number of oral stops even with the hard palate unrepaired, although with significantly fewer dentals/alveolars than are seen in peers without clefts. Differences in consonant inventory were correlated with hearing function.

Worrying About Death: An Initial Analysis of Young Adult Cancer Patients' Needs.

Young adults (YAs) with cancer may have a need to develop strategies to cope with their worries about death. This brief report presents findings from a pilot study on YAs' needs with regard to such issues. An anonymous, web-based questionnaire was posted with a total of 83 cancer patients taking the questionnaire (71 females and 12 males). Almost half of the participants thought about death every day. Since most of the participants had ended their treatment, this would appear to show that matters related to death remain an important issue after the YAs' cancer treatment has ended. The results show a need for YAs to talk about death, either with professionals or with peers.

The hers and his of prosociality across 10 countries.

Is there a 'more helpful' gender? The present research assessed gender differences in prosocial self-perceptions, prosocial behavioural intentions, and prosocial (transfer) behaviour in same- and other-gender interactions in 10 countries (N = 1,915). The present results showed negligible differences in the degree to which women and men saw themselves as prosocial. However, larger gender differences emerged in regard to prosocial behavioural intentions and prosocial (transfer) behaviours across different help contexts (i.e., same- vs. other-gender interactions). In a hypothetical work scenario, women reported greater prosocial behavioural intentions than men when the recipient of the help was of the same gender. In contrast, when the recipient of the help was of the other gender, men reported greater prosocial behavioural intentions than women. In addition, men transferred more than women to both same- and other-gender interaction partners in a prisoner's dilemma game. Taken together, the present findings suggest that there is no 'more helpful' gender. Instead, gender differences in prosociality are dynamic and contextual. Different theoretical perspectives are taken into consideration in discussing gender differences in the present research.