Pharmacological treatment of asthma in Sweden from 2005 to 2015.

OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting ß2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. RESULTS: Maintenance treatment with ICS together with long-acting ß2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

The human telomeric proteome during telomere replication.

Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by isolation of Proteins On Nascent DNA - which enables purification of proteins that associate with telomeres specifically during replication. In addition to the core replisome, we identify a large number of proteins that specifically associate with telomere replication forks. Depletion of several of these proteins induces telomere fragility validating their importance for telomere replication. We also find that at telomere replication forks the single strand telomere binding protein POT1 is depleted, whereas histone H1 is enriched. Our work reveals the dynamic changes of the telomeric proteome during replication, providing a valuable resource of telomere replication proteins. To our knowledge, this is the first study that examines the replisome at a specific region of the genome.

Primary care patients with mild or stable chronic obstructive pulmonary disease need more support in disease management: a secondary analysis of a cluster randomized controlled trial.

OBJECTIVE: Patient education based on the patient's individual needs and circumstances is known to be associated with positive changes in clinical outcomes in chronic obstructive pulmonary disease (COPD). We aimed to assess the levels of patients' subjective needs for information about COPD before and after their general practitioners had taken part in a COPD education. DESIGN: A secondary analysis of a cluster randomized controlled trial. SETTING: 22 PHCCs in Stockholm, Sweden. SUBJECTS: Randomly selected primary care patients with COPD in GOLD stages 2 and 3 (n = 293). OUTCOME MEASURES: Scores in the Lung Information Needs Questionnaire (LINQ) at baseline and 18 months, spirometry results, and self-reported, descriptive patient data. RESULTS: GPs' improved skills in COPD did not affect patients' self-management skills over time. In general, patients' information needs remained great in issues concerning diet, exercise and self-management. However, 43% of the patients reported reduced and 57% increased or unchanged information needs, over time. Reduced information needs were mainly associated with a high level of information needs at baseline (OR = 3.17 [95% CI 1.93-5.23], p < .01) and establishing contact with a physiotherapist (OR = 2.26 [95% CI 1.05-4.86], p = .038). Patients in a mild or stable phase of COPD with no recent exacerbations reported greater needs than those with unstable, deteriorated COPD. CONCLUSION: Patients' information needs are substantial in most areas of self-management of COPD, and seem to covary with the patient's current clinical status. Care providers should thus continuously be vigilant about offering all patients with COPD support and education. TRIAL REGISTRATION: Clinicaltrials.gov, 10 August 2014, Identifier NCT02213809.

Self-management skills are fundamental for patients living with a chronic condition such as chronic obstructive pulmonary disease (COPD).Improvements in general practitioners' (GPs) levels of knowledge about COPD management were not transferred to improvements in patients' self-management skills.Patients' needs for support in COPD were substantial, and moreover, they were not constant over time: the longer from the latest exacerbation, the less continuity of care and the greater needs for renewed support.To help patients master self-management of COPD and be better prepared for future deteriorations, health professionals should start COPD patient education early and continue with it regularly, regardless of the current clinical stage of the patient.

Factors associated with self-assessed asthma severity.

BACKGROUND: Asthma severity can be estimated as the level of medication needed to achieve asthma control or by the patient's subjective assessment. Factors associated with self-assessed asthma severity are still incompletely explored. AIM: The aim was to study factors associated with self-assessed moderate or severe asthma. METHOD: In total, 1828 randomly selected asthma patients from primary (69%) and secondary (31%) care, completed a questionnaire including items about patient characteristics, comorbidity, the Asthma Control Test (ACT), emergency care visits and a scale for self-assessed asthma severity. Logistic regression was used to analyze associations with the dependent variable, self-assessed moderate or severe asthma in the entire study population and stratified by sex. RESULTS: Of the patients, 883 (45%) reported having moderate or severe asthma. Factors independently associated with self-assessed moderate or severe asthma were age >60 years (OR [95% CI] 1.98 [1.37-2.85]), allergic rhino-conjunctivitis (1.43 [1.05-1.95]), sinusitis (1.45 [1.09-1.93]), poor asthma control as measured by ACT <20 (5.64 [4.45-7.16]) and emergency care visits the previous year (2.52 [1.90-3.34]). Lower level of education was associated with self-assessed moderate/severe asthma in women (1.16 [1.05-2.43]) but not in men (0.90 [0.65-1.25]), p for interaction = .012. CONCLUSION: Poor asthma control, allergic rhino-conjunctivitis, recent sinusitis and older age were independently associated with self-assessed moderate or severe asthma. Important implications are that comorbid conditions of the upper airways should always be considered as part of asthma management, and that elderly patients may need extra attention.

Quality of life and asthma control related to hormonal transitions in women's lives.

OBJECTIVES: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control. METHODS: The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤ 46 years (n = 338) and peri/postmenopausal 47-65 years (n = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months. RESULTS: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 (p < 0.001), lower asthma control with ACT score < 20, 72% vs. 28% (p < 0.001) and higher exacerbation frequency 44% vs. 20% (p = 0.004) compared with women without PMA. Women with irregular menstruation had higher exacerbation frequency than women with regular menstruation (p = 0.023). Hormonal contraceptives had no impact on QoL and asthma control. Peri/postmenopausal women with menopausal hormone therapy (MHT) had a clinically relevant lower Mini-AQLQ mean score compared to those without MHT, 4.9 vs 5.4 (p < 0.001), but no differences in asthma control. CONCLUSION: Women with PMA had lower QoL and more uncontrolled asthma than women without PMA. Peri/postmenopausal women with MHT had lower QoL than women without MHT. Individual clinical management of women with asthma may benefit from information about their sex hormone status.

Awareness of parental illness: a grounded theory of upholding family equilibrium in parents on long-term sick-leave in primary health care.

OBJECTIVE: To understand the main concern of chronically ill parents and how they resolve this concern in relation to their children. DESIGN: Grounded theory. SETTING: Three primary health care clinics in Sweden. SUBJECTS: Thirty-two interviewed parents and their children. MAIN OUTCOME MEASURES: Processes and typologies of upholding family relationships. RESULTS: A concern of chronically ill parents is sustaining family equilibrium, achieved through a process of upholding family relationships. How a parent upholds depends upon his/her comprehension of the illness and of their child's need for parenting. In response to the parent's upholding behaviours, children mirror the effect of the illness to the parent, the child's specific behaviour depending on his/her level of comprehension regarding the parent's illness. Their combined behaviours create an awareness context that may be closed, concealed, suspicious, conflicted, mutual pretence or open.When the parent drives and facilitates the evolution of comprehension, the context quickly evolves from closed to open. When the parent hinders the process by masking and resisting the child responds by probing and proving and they become locked into a suspicious or conflicted awareness context with high relational tension. To create family equilibrium the parent needs to reveal and facilitate the awareness process. CONCLUSION: Parents on long-term sick leave in primary health care can need assistance to facilitate the awareness context of themselves and their child.Implications: Clinicians can identify the current awareness context of their patient and help their patient towards increased understanding of their illness; their child's needs and the parental capacities needed to reveal the illness and its impacts.Key PointsChildren are affected when parents are ill; they wish for information on their parent's illness. Effective interventions are available in settings other than primary health care and possibilities seen by GPs and families in Scandinavian primary health care have been previously described. There is a knowledge gap in how parents view themselves and their parenting when ill in primary health care. An analysis grounded in interviews was needed to generate a hypothesis (theory) of parental concerns and behaviours.This theory proposes that an important concern of chronically ill parents is to sustain family equilibrium, which they attempt to do by upholding family relationships.Specific upholding behaviours include masking, resisting, colluding, and revealing. In response, children will engage in mirroring behaviours. Which paired behaviours are enacted will depend upon the respective levels of comprehension of parent and child regarding the illness and on the child's need for parenting. In their interactions, parent and child create one of six awareness contexts.Identifying the current awareness context in the family about chronic parental illness provides clinicians with a conceptual tool to better support those families locked in suspicious or conflicted awareness contexts.

Use of online knowledge base in primary health care and correlation to health care quality: an observational study.

BACKGROUND: Evidence-based information available at the point of care improves patient care outcomes. Online knowledge bases can increase the application of evidence-based medicine and influence patient outcome data which may be captured in quality registries. The aim of this study was to explore the effect of use of an online knowledge base on patient experiences and health care quality. METHODS: The study was conducted as a retrospective, observational study of 24 primary health care centers in Sweden exploring their use of an online knowledge base. Frequency of use was compared to patient outcomes in two national quality registries. A socio-economic Care Need Index was applied to assess whether the burden of care influenced the results from those quality registries. Non-parametric statistical methods and linear regression were used. RESULTS: Frequency of knowledge base use showed two groups: frequent and non-frequent users, with a significant use difference between the groups (p < 0.001). Outcome data showed significant higher values for all seven National Primary Care Patient Survey dimensions in the frequent compared to the non-frequent knowledge base users (p < 0.001), whereas 10 out of 11 parameters in the National Diabetes Register showed no differences between the groups (p > 0.05). Adjusting for Care Need Index had almost no effect on the outcomes for the groups. CONCLUSIONS: Frequent users of a national online knowledge base received higher ratings on patient experiences, but figures on health care quality in diabetes showed near to no correlation. The findings indicate that some effects may be attributed to the use of knowledge bases and requires a controlled evaluation.

Psychological treatments for return to work in individuals on sickness absence due to common mental disorders or musculoskeletal disorders: a systematic review and meta-analysis of randomized-controlled trials.

PURPOSE: Common mental disorders (CMDs) and musculoskeletal disorders are highly prevalent in the population and cause significant distress and disability, and high costs to society. The main objective of this systematic review and meta-analysis was to examine the outcome and comparative effectiveness of psychological interventions in reducing sickness absence (SA) due to CMDs or musculoskeletal disorders, compared to a waitlist control group, usual care or another clinical intervention. METHODS: We reviewed 3515 abstracts of randomized controlled trials published from 1998 to 2017. Of these, 30 studies were included in the analysis. RESULTS: The psychological interventions were overall more effective than treatment as usual in reducing SA (small effect sizes), but not compared to other clinical interventions. Results were similar for studies on CMDs and musculoskeletal pain. A few significant moderating effects were found for treatment-specific variables. However, these were  difficult to interpret as they pointed in different directions. CONCLUSION: There was a small but significant effect of psychological treatments in reducing SA. We identified areas of improvement such as methodological problems among the included studies and failure to specifically address RTW in the interventions that were evaluated. Clinical implications of the findings, and ways of improving methodological rigour of future studies are discussed.

COPD patients need more information about self-management: a cross-sectional study in Swedish primary care.

Objective: In Sweden, patients with chronic conditions, such as chronic obstructive pulmonary disease (COPD), often receive education at specialized nurse-led clinics at primary health care centers (PHCCs). Identifying patients' needs for information about COPD is the key to individualized care. This study aimed to assess self-reported needs for information about COPD in primary care patients with either moderate (GOLD 2) or severe (GOLD 3) COPD and identify patient characteristics and exacerbation patterns associated with the findings.Design: A cross-sectional study.Setting: Twenty-four PHCCs in Stockholm, Sweden.Subjects: Randomly selected primary care patients with COPD in GOLD stages 2 and 3 (n = 542).Main outcome measures: The Lung Information Needs Questionnaire (LINQ) was used to assess perceived information needs. Spirometry results and descriptive, self-reported data on patient factors such as exacerbation history, treatment, smoking, weight/height, comorbidities, health care contacts, education and symptoms were collected.Results: Overall, the greatest reported needs were for information about self-management and diet. GOLD 2 patients (68%) expressed greater needs for information than GOLD 3 patients (32%). We found significant associations between high information needs and patient-related factors such as 'No assigned GP' (OR = 4.32 [95% CI 2.65-7.05]) and 'No contact with COPD nurse in the past 12 months' (OR = 1.83 [95% CI 1.19-2.81]).Conclusion: COPD patients felt they knew too little about self-management of their disease. Low information needs were strongly associated with continuity in patient-GP consultations and moderately associated with contact with a COPD nurse. These associations were strongest in patients with moderate COPD.Key points: As patients with COPD often have multimorbidity, identifying patients' needs for information about COPD is essential to providing individualized patient education and care. In this study of 542 patients from 24 Swedish primary care centers, we found that:Patients with COPD, particularly those with moderate airflow limitation (i.e. GOLD 2) felt they needed more information about COPD than currently provided by health care professionals in primary care.Low information needs were strongly associated with continuity in patient-GP consultations and moderately associated with contact with a COPD nurse. GPs' part in COPD patient education should not be overlooked, as individualized COPD care relies on GPs' expertise in managing patients with multimorbidity.

COPD management by Swedish general practitioners - baseline results of the PRIMAIR study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death. Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease. Efficient strategies include early diagnosis, smoking cessation and multimodal treatment. AIM: To describe knowledge about and skills for managing COPD in GPs in Sweden. METHODS: Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD. Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests. RESULTS: Overall, 250 GPs at 34 PHCCs replied (89% response rate). Total mean score was 9.9 (maximum 26). Scores were highest on 'management of smoking cessation', 'follow-up after exacerbation' and 'diagnostic procedures'. Spirometry was used frequently, although interpretation skills were suboptimal. 'Management of maintenance therapy', 'management of multimorbidity' and 'interprofessional cooperation' had mediocre scores. Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC. CONCLUSIONS: Swedish GPs' knowledge of COPD and adherence to current guidelines seem insufficient. A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs. The relevance of this study to participants' actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation. To identify problem areas, we suggest using questionnaires prior to educational interventions. Key Points General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care. Swedish GPs' knowledge about COPD and adherence to current guidelines seem insufficient. Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation.

Time pressured deprioritization of COPD in primary care: a qualitative study.

OBJECTIVE: To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden. SETTING: Primary health care centres (PHCCs) in Stockholm, Sweden. SUBJECTS: A total of 59 PCPs. DESIGN: Semi-structured individual and focus-group interviews between 2012 and 2014. Data were analysed inspired by grounded theory methods (GTM). RESULTS: Time-pressured patient-doctor consultations lead to deprioritization of COPD. During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients. The reasons PCPs gave for deprioritizing COPD are: "Not becoming aware of COPD", "Not becoming concerned due to clinical features", "Insufficient local routines for COPD care", "Negative personal attitudes and views about COPD", "Managing diagnoses one at a time", and "Perceiving a patient's motivation as low''. CONCLUSIONS: De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity. A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines. KEY POINTS: Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care. A patient-doctor consultation offers a key opportunity to identify and provide COPD care. Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation. Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation. Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.

Differences in psychiatric comorbidity patterns in patients diagnosed with chronic stress-induced exhaustion disorder and depression - A cohort study in the total population of Region Stockholm.

The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to investigate common psychiatric and stress-related diagnoses, along with postviral fatigue, in individuals with prior stress-induced exhaustion disorder (SED) and prior depression compared to those without prior SED or depression, and to study whether the psychiatric comorbidity patterns differ. The study includes individuals in Region Stockholm who, in 2011, did not have a diagnosis of SED or depression. ICD-10 diagnosis of SED, depression, or both, recorded in 2012-2013, were compared to individuals without prior SED or depression in a cohort (n = 1,362,886), aged 18 to 65. Odds ratios (OR) with 99 % confidence intervals, adjusted for age and neighborhood socioeconomic status, were calculated for psychiatric disorders and post-viral fatigue in 2014-2022. Patients with prior SED showed associations primarily with stress related diagnoses, including acute stress reaction, reaction to severe stress, as well as post-COVID-19 and post-viral fatigue syndrome. These ORs were all larger for SED than depression. Depression was primarily associated with post-traumatic stress disorder (PTSD), alcohol related and substance use disorders, schizophrenia, schizotypal disorders, delusional disorders, manic episode, bipolar affective disorder, persistent mood disorder, neurotic disorder, borderline personality disorder, autistic disorder, Asperger's syndrome, attention -deficit hyperactivity disorder, attention-deficit disorders ADHD/ADD), and suicide attempt. These ORs were all higher for depression, although autistic disorders, ADHD/ADD and PTSD were also highly associated with prior SED (OR > 3.5). The divergent psychiatric comorbidity patterns suggest different underlying mechanisms and clinical prognosis.

High lifelong relapse rate of psychiatric disorders among women with postpartum psychosis.

BACKGROUND: The relapse rate for psychiatric disorders after postpartum psychosis is high. Apart from subsequent puerperal periods, previous studies have not examined when relapses in psychiatric disorders occur. In addition, little is known about the impact of certain individual factors on the risk of non-puerperal readmission among women with previous postpartum psychosis. AIMS: The first aim was to examine the association between non-puerperal readmission due to psychiatric disorders and years of follow-up (in total, 30 years) in women with postpartum psychosis. The second aim was to examine the impact of age, type of psychosis, previous hospitalization for psychiatric disorders and level of education on the risk of non-puerperal readmission due to psychiatric disorders. METHODS: All Swedish women aged 20-44 with postpartum psychosis (n =3140) were followed between 1975 and 2004 for non-puerperal readmission due to psychiatric disorders. A Cox frailty regression model was used to estimate hazard ratios for non-puerperal readmission. RESULTS: The risk of non-puerperal readmission, although gradually decreasing with time, remained high many years after the postpartum psychosis. The risk of non-puerperal readmission was significantly higher among women with schizophrenia, lower levels of education and previous psychiatric hospitalization. CONCLUSIONS: Postpartum psychosis is often part of a lifelong recurrent psychiatric disorder. Women with schizophrenia, lower levels of education and hospitalization due to a psychiatric disorder prior to postpartum psychosis have a higher risk of non-puerperal readmission. CLINICAL IMPLICATIONS: The findings constitute important knowledge for all healthcare workers encountering women with a previous postpartum psychosis.

Stress, depression, and risk of dementia - a cohort study in the total population between 18 and 65 years old in Region Stockholm.

BACKGROUND: Chronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive. METHODS: Cohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL). Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated. RESULTS: During the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22-4.91) in patients with chronic stress, 2.32 (99% CI 1.85-2.90) in patients with depression, and 4.00 (99% CI 1.67-9.58) in patients with chronic stress and depression. The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20-2.91) in patients with chronic stress, 2.85 (99% CI 2.53-3.22) in patients with depression, and 3.87 (99% CI 2.39-6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92-2.96). CONCLUSIONS: Documented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.

Comorbid Heart Disease in Patients with COPD is Associated with Increased Hospitalization and Mortality - A 15-Year Follow-Up.

Purpose: The aim of this study was to examine the association of comorbid heart disease, defined as chronic heart failure or ischemic heart disease, on all-cause and cause-specific hospitalization and mortality in patients with COPD over a period of nearly 15 years. Materials and Methods: The cohort study included patients with COPD from primary and secondary care in 2005 with data from questionnaires and medical record reviews. The Swedish Board of Health and Welfare provided hospitalization and mortality data from 2005 through 2019. Cox regression analyses, adjusted for sex, age, educational level, smoking status, BMI, exacerbations, dyspnea score and comorbid diabetes or hypertension, assessed the association of comorbid heart disease with all-cause and cause-specific time to first hospitalization and death. Linear regression analyses, adjusted for the same variables, assessed this association with hospitalization days per year for those patients that had been hospitalized. Results: Of the 1071 patients, 262 (25%) had heart disease at baseline. Cox regression analysis showed a higher risk of hospitalization for patients with heart disease for all-cause (HR (95% CI) 1.55; 1.32-1.82), cardiovascular (2.14; 1.70-2.70) and other causes (1.27; 1.06-1.52). Patients with heart disease also had an increased risk of all-cause (1.77; 1.48-2.12), cardiovascular (3.40; 2.41-4.78) and other (1.50; 1.09-2.06) mortality. Heart disease was significantly associated with more hospitalization days per year of all-cause (regression coefficient 0.37; 95% CI 0.15-0.59), cardiovascular (0.57; 0.27-0.86) and other (0.37; 0.12-0.62) causes. No significant associations were found between heart disease and respiratory causes of hospitalization and death. Conclusion: Comorbid heart disease in patients with COPD is associated with an increased risk for all-cause hospitalization and mortality, mainly due to an increase of hospitalization and death of cardiovascular and other causes, but not because of respiratory disease. This finding advocates the need of a strong clinical focus on primary and secondary prevention of cardiovascular disease in patients with COPD.

Does multimorbidity result in de-prioritisation of COPD in primary care?

The aim of this study was to describe factors associated with having COPD regularly reviewed in primary care by a nurse or physician and assess whether there was de-prioritisation for COPD in multimorbid patients. We defined de-prioritisation as not having at least one check-up by a physician during a two-year period. Among 713 COPD patients in the Swedish PRAXIS study, 473 (66%) had at least one check-up during the study period (ending in 2014). Patients with check-ups were more likely to have three or more comorbid conditions (31.9% vs. 24.6%) and exacerbations (35.1% vs. 21.7%) than those without. Compared with those without comorbidity, those with three or more diagnoses had increased relative risk ratios (and 95% CI) for consultations discussing COPD with only a physician (5.63 (2.68-11.79)), COPD-nurse only (1.67 (0.83-3.37)) or both (2.11 (1.09-4.06)). COPD patients received more frequent check-ups considering COPD if they had comorbidity or a history of exacerbations. We found no evidence of de-prioritisation for COPD in multimorbid patients.

Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts.

Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors' diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36-3.60), low educational level (OR 1.81; 1.09-3.02) and management in primary care (OR 2.28; 1.02-5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.

Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype. Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor's diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex. Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30-9.92]), stage 2 (3.42 [2.13-5.51]) and stage 3 (2.38 [1.46-3.88]) compared with stage 4, and with CAT score <10 (3.35 [2.34-4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28-0.79]) and (0.68 [0.48-0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030). Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.

Plasma levels of S100B and neurofilament light chain protein in stress-related mental disorders.

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P < 0.001) and healthy controls (P < 0.001). Self-rated symptoms of cognitive failures were positively correlated with levels of S100B (rs = 0.434, P = 0.005) as were depressive symptoms (rs = 0.319, P < 0.001). Plasma levels of astrocyte-derived EVs were correlated with levels of S100B (rs = 0.464, P < 0.001). Plasma levels of NF-L did not differ between the groups and were not correlated with symptom severity or EV levels. Thus, long-term stress without sufficient recovery and SED may be associated with raised plasma levels of S100B, which may be evidence of pathophysiological changes in astrocytes. The findings also support the hypothesis that plasma levels of S100B are associated with cognitive dysfunction.

Economic evaluation of return-to-work interventions for mental disorder-related sickness absence: two years follow-up of a randomized clinical trial.

OBJECTIVE: The objective was to (i) assess the long-term cost-effectiveness of acceptance and commitment therapy (ACT), a workplace dialog intervention (WDI), and ACT+WDI compared to treatment as usual (TAU) for common mental disorders and (ii) investigate any differences in cost-effectiveness between diagnostic groups. METHODS: An economic evaluation from the healthcare and limited welfare perspectives was conducted alongside a randomized clinical trial with a two-year follow-up period. Persons with common mental disorders receiving sickness benefits were invited to the trial. We used registry data for cost analysis alongside participant data collected during the trial and the reduction in sickness absence days as treatment effect. A total of 264 participants with a diagnosis of depression, anxiety, or stress-induced exhaustion disorder participated in a two-year follow-up of a four-arm trial: ACT (N=74), WDI (N=60), ACT+WDI (N=70), and TAU (N=60). RESULTS: For all patients in general, there were no statistically significant differences between interventions in terms of costs or effect. The subgroup analyses suggested that from a healthcare perspective, ACT was a cost-effective option for depression or anxiety disorders and ACT+WDI for stress-induced exhaustion disorder. With a two-year time horizon, the probability of WDI to be cost-saving in terms of sickness benefits costs was 80% compared with TAU. CONCLUSIONS: ACT had a high probability of cost-effectiveness from a healthcare perspective for employees on sick leave due to depression or anxiety disorders. For participants with stress-induced exhaustion disorder, adding WDI to ACT seems to reduce healthcare costs, while WDI as a stand-alone intervention seems to reduce welfare costs.