Risk Factors Associated with Asthma Control and Quality of Life in Patients with Mild Asthma Without Preventer Treatment, a Cross-Sectional Study.

Purpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment. Patients and Methods: Patients aged 18-75 years with a doctor's diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥20 points and no exacerbation and uncontrolled asthma as ACT<20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥6) and insufficient QoL (mean score <6). Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL. Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.

Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma. We studied patients with asthma diagnosis 18­75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL. Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.

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.

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.

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.

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.

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.

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.

Outcomes of psychiatric interviews and self-rated symptom scales in people on sick leave for common mental disorders: an observational study.

OBJECTIVES: To investigate the correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Secondary aims were to investigate length of sick leave by diagnoses on sick leave certificates, diagnoses made in structured interviews and symptom severity. DESIGN: Observational study consisting of a secondary analysis of data from a randomised controlled trial and an observational study. SETTING: The regions of Stockholm and Västra Götaland, Sweden. PARTICIPANTS: 480 people on sick leave for common mental disorders. INTERVENTIONS: Participants were examined with structured psychiatric interviews and self-rated symptom severity scales. OUTCOME MEASURES: (1) Sick leave certificate diagnoses, (2) diagnoses from the Mini International Neuropsychiatric Interview and the Self-rated Stress-Induced Exhaustion Disorder (SED) Instrument (s-ED), (3) symptom severity (Montgomery-Asberg Depression Rating Scale-self-rating version and the Karolinska Exhaustion Disorder Scale) and (4) number of sick leave days. RESULTS: There was little correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Many participants on sick leave for SED, anxiety disorder or depression fulfilled criteria for other mental disorders. Most on sick leave for SED (76%) and anxiety disorder (67%) had depression (p=0.041). Length of sick leave did not differ by certificate diagnoses. Participants with SED (s-ED) had longer sick leave than participants without SED (144 vs 84 days; 1.72 (1.37-2.16); p<0.001). More severe symptoms were associated with longer sick leave. CONCLUSION: Diagnoses on sick leave certificates did not reflect the complex and overlapping nature of the diagnoses found in the structured psychiatric interviews. This finding is relevant to the interpretation of information from health data registers, including studies and guidelines based on these data. A result of clinical interest was that more severe symptoms predicted long-term sick leave better than actual diagnoses.

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.

MicroRNA-365 regulates human cardiac action potential duration.

Abnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels. Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes show that elevation of miR-365 significantly prolongs action potential duration in myocytes derived from a Short-QT syndrome patient, whereas specific inhibition of miR-365 normalizes pathologically prolonged action potential in Long-QT syndrome myocytes. Transcriptome analyses in these cells at bulk and single-cell level corroborate the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional action potential-regulating genes by this microRNA. Whole-cell patch-clamp experiments confirm miR-365-dependent regulation of repolarizing ionic current Iks. Finally, refractory period measurements in human myocardial slices substantiate the regulatory effect of miR-365 on action potential in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac action potential duration by targeting key factors of cardiac repolarization.

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.

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.

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.

Isoforms of soluble vascular endothelial growth factor in stress-related mental disorders: a cross-sectional study.

Vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of stress-related mental disorders. However, VEGF levels have seldom been compared across mental disorders and never by isoforms. Pathophysiological processes involving leakage of astrocyte-derived extracellular vesicles (EVs) across the blood-brain barrier could be associated with VEGF levels in patients with stress-related mental disorders. This cross-sectional study compared plasma levels of VEGF121, VEGF165, and VEGF121 + VEGF165 (VEGFtotal) in patients with stress-induced exhaustion disorder (SED) (n = 31), patients with major depressive disorder (MDD) (n = 31), and healthy controls (n = 61). It also analyzed the correlation between VEGF and astrocyte-derived EVs in plasma. An enzyme-linked immunosorbent assay (ELISA) was used to measure VEGF121 and VEGF165 in citrate plasma, and flow cytometry was used to measure astrocyte-derived EVs in plasma. The mean concentration of soluble VEGF121 (sVEGF121) was significantly higher in patients with SED than healthy controls (P = 0.043). Mean sVEGF165 was significantly lower in patients with MDD than patients with SED (P = 0.004) or healthy controls (P = 0.037). Mean sVEGFtotal was significantly higher in patients with SED than in patients with MDD (P = 0.021) and also higher in patients with SED than healthy controls (P = 0.040). Levels of sVEGF121 were positively correlated with levels of astrocyte-derived EVs only in patients with SED (P = 0.0128). The same was true of levels of sVEGFtotal and astrocyte-derived EVs (P = 0.0046). Differing levels of VEGF isoforms may reflect different pathophysiological mechanisms in SED and MDD. Further research is needed to better understand the potential roles of VEGF isoforms and astrocyte-derived EVs in mental disorders.

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.