Ultrafast structural changes within a photosynthetic reaction centre.

Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography1 using an X-ray free-electron laser2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions.

Virtual discovery of melatonin receptor ligands to modulate circadian rhythms.

The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light-dark cycle1-4. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep5,6 and depression1-4,7-9. Despite their importance, few in vivo active MT1-selective ligands have been reported2,8,10-12, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT1 crystal structure, prioritizing structural fit and chemical novelty. Of these compounds, 38 high-ranking molecules were synthesized and tested, revealing ligands with potencies ranging from 470 picomolar to 6 micromolar. Structure-based optimization led to two selective MT1 inverse agonists-which were topologically unrelated to previously explored chemotypes-that acted as inverse agonists in a mouse model of circadian re-entrainment. Notably, we found that these MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3-1.5 h when given at subjective dusk, an agonist-like effect that was eliminated in MT1- but not in MT2-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT1-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries.

Publisher Correction: Structural basis of ligand recognition at the human MT1 melatonin receptor.

Change history: In this Letter, the rotation signs around 90°, 135° and 15° were missing and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online.

XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity.

The human MT1 and MT2 melatonin receptors1,2 are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns3. Drug development efforts have targeted both receptors for the treatment of insomnia, circadian rhythm and mood disorders, and cancer3, and MT2 has also been implicated in type 2 diabetes4,5. Here we report X-ray free electron laser (XFEL) structures of the human MT2 receptor in complex with the agonists 2-phenylmelatonin (2-PMT) and ramelteon6 at resolutions of 2.8 Å and 3.3 Å, respectively, along with two structures of function-related mutants: H2085.46A (superscripts represent the Ballesteros-Weinstein residue numbering nomenclature7) and N862.50D, obtained in complex with 2-PMT. Comparison of the structures of MT2 with a published structure8 of MT1 reveals that, despite conservation of the orthosteric ligand-binding site residues, there are notable conformational variations as well as differences in [3H]melatonin dissociation kinetics that provide insights into the selectivity between melatonin receptor subtypes. A membrane-buried lateral ligand entry channel is observed in both MT1 and MT2, but in addition the MT2 structures reveal a narrow opening towards the solvent in the extracellular part of the receptor. We provide functional and kinetic data that support a prominent role for intramembrane ligand entry in both receptors, and suggest that there might also be an extracellular entry path in MT2. Our findings contribute to a molecular understanding of melatonin receptor subtype selectivity and ligand access modes, which are essential for the design of highly selective melatonin tool compounds and therapeutic agents.

Structural basis of ligand recognition at the human MT1 melatonin receptor.

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms1 by synchronization to environmental cues and is involved in diverse physiological processes2 such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function3. Melatonin is formed in the pineal gland in a light-regulated manner4 by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2)3,6. Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden7. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids8,9, and is one of the most popular supplements in the United States10. Here, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon11, two melatonin analogues, and the mixed melatonin-serotonin antidepressant agomelatine12,13. The structure of MT2 is described in an accompanying paper14. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer. The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Our structures provide an unexpected example of atypical ligand entry for a non-lipid receptor, lay the molecular foundation of ligand recognition by melatonin receptors, and will facilitate the design of future tool compounds and therapeutic agents, while their comparison to 5-HT receptors yields insights into the evolution and polypharmacology of G-protein-coupled receptors.

Post-diagnostic support for persons with young-onset dementia - a retrospective analysis based on data from the Swedish dementia registry SveDem.

BACKGROUND: Approximately 3.9 million persons worldwide have young-onset dementia. Symptoms related to young-onset dementia present distinct challenges related to finances, employment, and family. To provide tailored support, it is important to gain knowledge about the formal support available for persons with young-onset dementia. Therefore, this paper aims to describe formal support for persons with young-onset dementia in Sweden and the factors influencing this support. METHODS: This retrospective study used data on persons under 65 years of age (n = 284) from The Swedish Registry for Cognitive/Dementia Disorders (SveDem) between 2021 and 2022. SveDem was established to monitor the quality of dementia care in Sweden. Characteristics of participants were obtained, including age, sex, dementia diagnosis, MMSE, medications, accommodation, and care setting. Descriptive statistics and logistic regression were used to test for associations between participant characteristics and post-diagnostic support. RESULTS: Information and educational support were usually offered to the person with young-onset dementia (90.1%) and their family (78.9%). Approximately half of the sample were offered contact with a dementia nurse (49.3%), counsellor (51.4%), or needs assessor (47.9%). A minority (28.5%) were offered cognitive aids. Six regression models were conducted based on participant characteristics to predict the likelihood that persons were offered support. Support was not predicted by age, sex, children at home, accommodation, or medications. Lower MMSE scores (p < .05) and home help (p < .05) were significantly associated with offer of a needs assessor. Living together was a significant predictor (p < .01) for information and educational support offered to the family. Care setting significantly predicted (p < .01) an offer of information and educational support for the person and family members, as well as contact with a counsellor. CONCLUSION: This study indicates potential formal support shortages for persons with young-onset dementia in some areas of dementia care. Despite equal support across most characteristics, disparities based on care setting highlight the importance of specialised dementia care. Pre-diagnostic support is minimal, indicating challenges for persons with young-onset dementia to access these services before diagnosis. While our study has identified areas in need of improvement, we recommend further research to understand the changing support needs of those with young-onset dementia.

Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.

OBJECTIVES: To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). METHODS: IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. RESULTS: Peptide GPI293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI293-307 epitopes, and high affinity anti-GPI293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI293-307-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI293-307 antibodies. CONCLUSIONS: We have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.

Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.

OBJECTIVE: Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR. METHODS: Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3). RESULTS: Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036). CONCLUSIONS: Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).

Application of the International Classification of Functioning, Disability and Health (ICF) in dementia research and practice: A scoping review.

OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) endorsed by the World Health Organization provides a conceptual framework for describing functioning and disability based on a biopsychosocial model. Although dementia is one of the leading causes of disability, yet little is known on the extent to how the ICF has been utilized in dementia research and practice. The study aimed to examine and map the current applications of the ICF with dementia from a body of earlier studies and to explore the potential use in person-centred dementia care. METHODS: The Arksey and O'Malley framework was used to guide the searching, selecting, and synthesizing process. The scoping review was reported following The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines. RESULTS: A total of 34 studies were included. The applications of ICF were classified into 4 themes: (1) in clinical practice and the education of health professionals (n = 20); (2) community support services and income support (n = 3); (3) population-based, census, or survey data (n = 10); (4) advocacy and empowerment purposes (n = 1). CONCLUSION: The ICF has made a major impact on dementia in clinical settings. Findings strongly support applying the ICF to person-centered dementia care. In the future, more empirical studies are needed to expand the scope of ICF use in dementia research and practice.

Needs of family members caring for stroke survivors in china: A deductive qualitative content analysis study by using the caregiver task inventory-25.

BACKGROUND: In China, family caregivers are usually the main carers of relatives after stroke due to traditional Chinese culture and the limited development of the primary healthcare system. This responsibility often results in burdens and negative health outcomes. However, family caregivers seldom receive support. To improve informal care, as well as the health and well-being of family caregivers, it is important to identify their needs. OBJECTIVE: This study aimed to deductively explore the needs of family members caring for stroke survivors in China. METHODS: Twenty-six semi-structured interviews were performed with family caregivers of stroke survivors who were selected from one city and three communities by purposive sampling. A deductive qualitative content analysis method was performed by using the Caregiver Task Inventory-25 (CTI-25), an instrument measuring the needs of family caregivers, as a framework. RESULTS: All subscales, as well as all belonging items in the CTI-25, were identified in the present study, meaning that the family caregivers had needs related to learning to cope with new role, providing care according to care-receiver's needs, managing own emotional needs, appraising supportive resources, and balancing caregiving needs and one's own needs. Moreover, needs related to financial support, both direct and indirect, were identified but not part of the CTI-25. CONCLUSION: These findings identified that family caregivers of stroke survivors in China had various needs, which is important knowledge when assessing needs and improving health care for family caregivers. Cultural adjustments and modifications should be made if CTI-25 is used in mainland China. This study also indicated a comprehensive and holistic perspective (individual, community, and social level) when identifying, assessing needs or implementing interventions to support family caregivers.

A Bright Future for Serial Femtosecond Crystallography with XFELs.

X-ray free electron lasers (XFELs) have the potential to revolutionize macromolecular structural biology due to the unique combination of spatial coherence, extreme peak brilliance, and short duration of X-ray pulses. A recently emerged serial femtosecond (fs) crystallography (SFX) approach using XFEL radiation overcomes some of the biggest hurdles of traditional crystallography related to radiation damage through the diffraction-before-destruction principle. Intense fs XFEL pulses enable high-resolution room-temperature structure determination of difficult-to-crystallize biological macromolecules, while simultaneously opening a new era of time-resolved structural studies. Here, we review the latest developments in instrumentation, sample delivery, data analysis, crystallization methods, and applications of SFX to important biological questions, and conclude with brief insights into the bright future of structural biology using XFELs.

Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis. A case-control study.

OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. METHODS: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities. RESULTS: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3-7.7) years and MPO-ANCA+ 2.0 (0.9-3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively). CONCLUSION: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

Diagnostic accuracy and clinical applicability of the Swedish version of the 4AT assessment test for delirium detection, in a mixed patient population and setting.

BACKGROUND: Delirium is common in older hospitalized patients. It has serious consequences e.g., poor health outcomes, mortality and increased costs. Despite that, many cases are undetected. Early detection of delirium is important in improving outcomes and use of assessment tools improves detection rates. The 4AT is a brief screening tool for delirium detection, which has not previously been translated into Swedish. The study aim was to evaluate diagnostic accuracy and clinical applicability of a Swedish version of the screening tool 4AT for delirium detection. METHOD: This diagnostic test accuracy study used a quantitative and a qualitative approach and evaluated the patients' and the health care professionals' experiences of the tool. Study included 200 patients ≥65 years from a university hospital and a county hospital in two Swedish regions. Medical specialties were geriatric stroke/neurology, geriatric multimorbidity, severe cognitive impairment, orthopaedic, and urology. The translated 4AT was tested against the reference standard DSM-IV-TR criteria, based on the Organic Brain Syndrome scale and patient records. The 4AT was assessed simultaneously and independently by two assessors. Additionally, data was collected through patient record reviews, and questions about applicability to the patients (n = 200) and the assessors (n = 37). Statistical analyses, and qualitative content analyses were conducted. RESULTS: By reference standard 18% had delirium, and by 4AT 19%. The overall percent agreement was 88%, AUROC 0.808, sensitivity 0.70 (95% CI 0.51-0.84) and specificity 0.92 (95% CI 0.87-0.96). In the ward for severe cognitive impairment (n = 63) the 4AT was less sensitive and less specific. In the other wards (n = 132) sensitivity was 0.77 (95% CI 0.50-0.93), specificity 0.93 (95% CI 0.87-0.97), and AUROC 0.848. Interrater reliability (Kappa) was 0.918, p = < 0.001 (n = 144). The 4AT was well tolerated by patients, easy to use for health care professionals, and took a few minutes to conduct. CONCLUSION: The Swedish version of 4AT is an accurate and applicable tool to use in clinical practice for detecting delirium in hospitalized patients across different medical specialities, and to use by different professionals and levels of seniority. To improve patient outcomes, we recommend the 4AT to be incorporated in clinical practice in health care settings in Sweden.

Evaluation of older persons' medications: a critical incident technique study exploring healthcare professionals' experiences and actions.

BACKGROUND: Older persons with polypharmacy are at increased risk of harm from medications. Therefore, it is important that physicians and nurses, together with the persons, evaluate medications to avoid hazardous polypharmacy. It remains unclear how healthcare professionals experience such evaluations. This study aimed to explore physicians' and nurses' experiences from evaluations of older persons' medications, and their related actions to manage concerns related to the evaluations. METHOD: Individual interview data from 29 physicians and nurses were collected and analysed according to the critical incident technique. RESULTS: The medication evaluation for older persons was influenced by the working conditions (e.g. healthcare professionals' clinical knowledge, experiences, and situational conditions) and working in partnership (e.g. cooperating around and with the older person). Actions taken to manage these evaluations were related to working with a plan (e.g. performing day-to-day work and planning for continued treatment) and collaborative problem-solving (e.g. finding a solution, involving the older person, and communicating with colleagues). CONCLUSION: Working conditions and cooperation with colleagues, the older persons and their formal or informal caregivers, emerged as important factors related to the medication evaluation. By adjusting their performance to variations in these conditions, healthcare professionals contributed to the resilience of the healthcare system by its capacity to prevent, notice and mitigate medication problems. Based on these findings, we hypothesize that a joint plan for continued treatment could facilitate such resilience, if it articulates what to observe, when to act, who should act and what actions to take in case of deviations from what is expected.

Using aggregated data from Swedish national quality registries as tools to describe health conditions of older adults with complex needs.

BACKGROUND: Combining National Quality Registries (NQRs) with existing National Health Registries (NHRs) might make it possible to get a wider picture of older adults health situation. The aim was to examine the feasibility of aggregating data across different NQRs and existing NHRs to explore the possibility to investigate trajectories and patterns of disease and care, specifically for the most ill older adults. METHOD: A Swedish twin population (N = 44,816) was linked to nine NQRs and four NHRs. A descriptive mixed-method study was performed. A manifest content analysis identified which health parameters were collected from each NQR. Factor analysis identified patterns in representation across NQRs. Two case studies illustrated individual trajectories of care by using NQRs and NHRs. RESULTS: About 36% of the population was registered in one or more NQRs. NQRs included 1849 variables that were sorted into 13 categories with extensive overlap across the NQRs. Health and function variables were identified, but few social or cognitive variables. Even though most individuals demonstrated unique patterns of multi-morbidities, factor analysis identified three clusters of representation in the NQRs with sufficient sample sizes for future investigations. The two cases illustrated the possibility of following patterns of disease and trajectories of care. CONCLUSIONS: NQRs seem to be a significant source for collecting data about a population that may be underrepresented in most research on aging because of their age and poor health. However, NQRs are primarily disease related, and further development of the registries to maximize coverage and utility is needed.

Consequences of the Covid-19 virus on individuals receiving homecare services in Norway. A qualitative study of nursing students' reflective notes.

BACKGROUND: Reflective notes in nursing education can facilitate students' understanding of how individuals in need of home healthcare services experience unfamiliar situations, such as a pandemic. The aim of this study is to describe the consequences of the COVID-19 virus for individuals receiving homecare services through the eyes of nursing students. METHODS: This is a qualitative descriptive study using content analysis to examine reflection notes from 17 nursing students in their last year of academic studies while undertaking home healthcare service training. RESULTS: Our study shows students' reflections on the consequences of the COVID-19 virus on individuals needing home healthcare services and their families. The analysis reveals three categories that described the effect of the virus according to students' reflections: i) how social life became restricted and only includes the closest family members and home healthcare staff (declining social circle), ii) how family members take on more responsibility to care for the individual and the pronounced impact of this on the day-to-day lives of the individual's next of kin (expanding responsibility of care), and iii) actions and reactions related to preventing the spread of the virus (dealing with the invisible threat). CONCLUSIONS: Students' reflection notes show that COVID-19 had major consequences, not only on the individuals receiving home healthcare services, but also on their relatives and on home healthcare staff.

Oral health is essential for quality of life in older adults: A Swedish National Quality Register Study.

OBJECTIVE: To examine the relationship between QoL and oral health from two Swedish national quality registries (NQRs). BACKGROUND: Oral health plays an important part in general health, which might also affect QoL. No studies have examined the relationships between QoL and oral health in late adulthood based on aggregated data from Swedish NQRs. MATERIAL AND METHODS: Four NQRs incorporated the EQ-5D, which assesses 5 aspects of QoL: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Items from the Revised Oral Assessment Guide, obtained from the NQR Senior Alert, were used to identify older adults at risk for oral health issues. RESULTS: A total of 510 individuals had data on all relevant variables. Analyses indicated significantly higher QoL for individuals without risk of oral health problems (M = -0.15 (SD = 1.01)), compared to those with risk (M = -0.75 (SD = 1.52)). Logistic regression analysis showed that lower QoL (OR = 0.69 (0.49, 0.97)), mental status (OR = 0.37 (0.19, 0.71)), lower self-rated health (OR = 0.59 (0.42, 0.85)) and higher age (OR = 1.07 (1.01, 1.13)) were significantly related to risk of oral health problems. Higher BMI (OR = 1.13 (0.99, 1.30)), living alone (OR = 2.37 (0.93, 6.06)) and more years of education (OR = 1.15 (1.01, 1.31)) were associated with higher risk of oral health problems. CONCLUSIONS: Oral health is a significant component of quality of life in late adulthood. NQRs are of value for healthy ageing research in populations that may be underrepresented in research studies.

Health- and social care in the last year of life among older adults in Sweden.

BACKGROUND: In the last years of life, burden of disease and disability and need of health- and social care often increase. Social, functional and psychological factors may be important in regard to social- and health care utilization. This study aims to describe use of health- and social care during the last year of life among persons living in ordinary housing or in assisted living facilities. METHODS: A retrospective study examining health- and social care utilization during their last year of life, using a subsample from the Swedish twin registries individually linked to several Swedish national quality registries (NQR). Persons that died during 2008-2009 and 2011-2012 (n = 1518) were selected. RESULTS: Mean age at death was 85.9 ± 7.3 (range 65.1-109.0). Among the 1518 participants (women n = 888, 58.5%), of which 741 (49%) were living in assisted living facilities and 1061 (69.9%) had at least one hospitalization during last year of life. The most common causes of death were cardiovascular disease (43.8%) and tumors (15.3%). A multivariable logistic regression revealed that living in ordinary housing, younger age and higher numbers of NQR's increased the likelihood of hospitalization. CONCLUSIONS: Persons in their last year of life consumed high amount of health- and social care although 12% did not receive any home care. Married persons received less home care than never married. Persons living in ordinary housing had higher numbers of hospitalizations compared to participants in assisted living facilities. Older persons and persons registered in fewer NQR's were less hospitalized.

Experiences and Management of Incidents That Influence Sleep in Patients With Cardiovascular Disease and Insomnia.

BACKGROUND: Insomnia is a global problem and an important risk factor for patients living with cardiovascular disease (CVD), causing poor well-being and worsening disease prognosis. Yet, there is a lack of effective intervention strategies targeting sleep problems. To deliver patient-centered interventions and achieve good quality of sleep for this group, the own experiences of patients with CVD need to be understood. OBJECTIVE: The aim of this study was to describe experiences that influence the sleep situation and management of sleep problems among patients with CVD and insomnia. METHOD: A qualitative descriptive design with critical incident technique methodology was used. Twenty patients (13 men and 7 women; mean age, 73 years; range, 47-83 years) with single or multiple verified CVD diagnoses and insomnia were included. RESULTS: Four underlying categories of sleep disruptors were identified: cognitive, social, physical, and behavioral. Participants experienced distress from the heart condition at night, physically and cognitively, with high levels of concern about its consequences for themselves and their families. Participants' sleep management preferences and responses included cognitive, behavioral, and pharmacological management strategies. Participants preferred their own nonpharmacological insomnia management over professional advice. CONCLUSION: Patients with CVD and insomnia experienced both physical and cognitive distress from their heart condition and chose to adopt nonpharmacological insomnia management. Tailored professional support is needed to change precipitating behavioral factors to be able to treat insomnia, improve sleep, reduce symptom burden, and enhance quality of life.

Exercise capacity, physical activity, and health-related quality of life in adults with CHD.

OBJECTIVES: The aim of this study was to assess exercise capacity, physical activity, and health-related quality of life within a broad and unselected group of adults with CHD. DESIGN: From April 2009 to February 2014, 1310 patients were assessed for suitability to participate in this single-centre cross-sectional study. Seven hundred and forty-seven (57%) patients were included, performed a submaximal bicycle test, and answered questionnaires regarding physical activity and health-related quality of life. Exercise capacity, physical activity, and health-related quality of life were compared with reference values and correlations were studied. RESULTS: The exercise capacities of men and women with CHD were 58.7 and 66.3%, respectively, of reference values. Approximately, 20-25% of the patients did not achieve the recommended amount of physical activity. In addition, men scored significantly less points on 7 out of 10 scales of health-related quality of life and women in 6 out of 10 scales, compared with reference values. The strongest correlation was between exercise capacity and the Short Form-36 (physical function). CONCLUSIONS: Exercise capacity was impaired in all adults with CHD, including those with less complicated CHD. One-quarter of the patients did not achieve the recommended levels of physical activity. Exercise tests followed by individualised exercise prescriptions may be offered to all patients with CHD aiming to increase exercise capacity, levels of physical activity, improve health-related quality of life, and reduce the risk of acquired life-style diseases.