Health-related quality of life in psychiatric outpatients: a cross-sectional study of associations with symptoms, diagnoses, and employment status.

BACKGROUND: This cross-sectional study aimed to explore health-related quality of life (HRQoL) in a large heterogeneous patient sample seeking outpatient treatment at a specialist mental health clinic. METHOD: A sample of 1947 patients with common mental disorders, including depressive-, anxiety-, personality-, hyperkinetic- and trauma-related disorders, completed the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) to assess HRQoL. We investigated clinical and sociodemographic factors associated with the EQ-5D index and the EQ Visual Analogue Scale (VAS) using regression analyses. RESULTS: The sample reported lower HRQoL compared with the general population and primary mental health care patients. Sick leave, disability pension, work assessment allowance, and more symptoms of anxiety and depression were associated with lower EQ-5D index and EQ VAS scores. Furthermore, being male, use of pain medication and having disorders related to trauma were associated with reduced EQ-5D index scores, while hyperkinetic disorders were associated with higher EQ-5D index scores. CONCLUSION: HRQoL of psychiatric outpatients is clearly impaired. This study indicated a significant association between employment status, symptom severity, and HRQoL in treatment-seeking outpatients. The findings highlight the importance of assessing HRQoL as part of routine clinical assessment.

Is the Norwegian stepped care model for allocation of patients with mental health problems working as intended? A cross-sectional study.

OBJECTIVE: Stepped care models are frameworks for mental health care systems in several countries. According to Norwegian guidelines, individuals with mental health problems of mild severity should be treated in community mental health services, moderate severity in specialist mental health services, while complex/severe problems are often a shared responsibility. This study investigated whether patients are allocated as intended. METHODS: In a cross-sectional study, 4061 outpatients recruited from community- and specialist mental health services reported demographic variables, symptoms of anxiety/depression, functional impairment, health status, and sick leave status. The community sample consisted of two subsamples: mild/moderate problems and complex problems. RESULTS: There was substantial overlap (80%-99%) of symptoms, impairment, and health between community- and specialist mental health services. More impairment, worse health, lower age, and being male were associated with treatment at specialist level compared to community mild/moderate. Better health, being in a relationship, and lower age were associated with specialized treatment compared to community complex group. CONCLUSION: The limited association between treatment level and symptoms and functional impairment reveals inconsistencies between treatment guidelines and clinical practice. How the existing organization affects patient outcomes and satisfaction should be investigated further.

Clinically representative therapy for Nordic adult outpatients with common mental health problems: A systematic review and meta-analysis.

There is a knowledge gap regarding clinically representative therapy given in routine settings, that is treatment as usual (TAU), for patients with common mental health problems (CMHP). This review and meta-analysis aimed to investigate what characterizes clinically representative therapy in Nordic routine clinics and meta-analyze the outcome of such treatment. Databases (PubMed, EMBASE, PsychINFO, and SveMed+) were searched for TAU, CMHP, and Nordic countries, together with backward and forward search in Scopus (7 November 2022). Studies were either randomized controlled trials (RCT) or open trials, using prospective study designs, examining heterogeneous outpatient groups in routine treatment. Within- and between-group effect sizes (ES), using random effects model, and moderator analyses were calculated. Eleven studies (n = 1,413), demonstrated a small to moderate within-group ES with high heterogeneity (g = 0.49, I2 = 90%). ESs in RCTs were significantly smaller than in open trials. TAU had a marginally smaller ES (g = -0.21; adjusted for publication bias g = -0.06) compared to a broad set of clinical interventions. Clinically representative therapy in the Nordic countries demonstrated a wide variety of characteristics and also a marginally lower ES compared to other interventions. The ESs were smaller than other meta-analyses examining evidence-based treatments in routine treatment.

Examination of the knowledge gap of return-to-work outcomes in routine outpatient treatment for common mental disorders: a systematic review.

Objective: Little is known about the effects of routine mental health care on return-to-work (RTW) outcomes. This systematic review aimed to summarize and evaluate the effects of clinical representative psychotherapy on RTW among patients with a common mental disorder (CMD), treated within public mental health care. Method: A systematic search was conducted using PubMed, PsycINFO, Embase, and SveMED+. Primary outcomes were RTW, sick leave status, or self-reported work functioning. Studies limited to specific treatments and/or specific patient groups were excluded. Results: Out of 1,422 records, only one article met the preregistered inclusion criteria. After broadening of criteria, a total of nine studies were included. Six were randomized controlled trials (RCT), two were register-based studies, and one was a quasi-experimental study. Descriptions of treatment duration and intensity of usual care were rarely specified but ranged from a few sessions to 3 years of psychotherapy. In the RCTs, two studies favored the intervention, one favored routine care, and three found no difference between conditions. Choice of outcomes differed greatly and included RTW rates (full or partial), number of days until RTW, change in sick leave status, and net days/months of work absence. Time points for outcome assessment also varied greatly from 3 months to 5 years after treatment. Conclusion: There is inconclusive evidence to establish to what extent routine mental healthcare is associated with improved RTW outcomes for patients with CMD. There is a need for more and better clinical trials and naturalistic studies detailing the content of routine treatment and its effect on RTW. Systematic review registration: This study was pre-registered at PROSPERO (CRD42022304967), https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304967.

Symptoms and prevalence of common mental disorders in a heterogenous outpatient sample: an investigation of clinical characteristics and latent subgroups.

BACKGROUND: Patient-reported outcome measures (PROM) provide clinicians with information about patients' perceptions of distress. When linked with treatment and diagnostic registers, new information on common mental health disorders (CMHD) and service use, may be obtained, which might be useful clinically and for policy decision-making. This study reports the prevalence of CMHD and their association with PROM severity. Further, subgroups of self-reported symptoms of depression and anxiety were examined, and their association with clinician-assessed mental disorders, functional impairment, and service use. METHODS: In a cohort study of 2473 (63% female) outpatients, CMHD was examined with pre-treatment scores of self-reported depression and anxiety, and the number of assessments and psychotherapy appointments one year after treatment start. Factor mixture modelling (FMM) of anxiety and depression was used to examine latent subgroups. RESULTS: Overall, 22% of patients with a CMHD had an additional comorbid mood/anxiety disorder, making the prevalence lower than expected. This comorbid group reported higher symptoms of anxiety and depression compared to patients with non-comorbid disorders. FMM revealed three classes: "anxiety and somatic depression" (33%), "mixed depression and anxiety" (40%), and "cognitive depression" (27%). The anxiety and somatic depression class was associated with older age, being single and on sick leave, higher probability of depressive-, anxiety-, and comorbid disorders, having more appointments and higher functional impairment. Although the cognitive depression class had less somatic distress than the mixed depression and anxiety class, they reported more functional impairment and had higher service use. CONCLUSION: The results show that higher levels of somatic symptoms of depression could both indicate higher and lower levels of functional impairment and service use. A group of patients with high somatic depression and anxiety was identified, with severe impairment and high service needs. By gaining insights into CMHD factors' relation with clinical covariates, self-reported risk factors of depression and anxiety could be identified for groups with different levels of aggravating life circumstances, with corresponding service needs. These could be important symptom targets in different groups of patients.

Sociodemographic factors and use of pain medication are associated with health-related quality of life: results from an adult community mental health service in Norway.

PURPOSE: Health-related quality of life (HRQoL) is an important aspect of mental health outcomes. There are few studies on HRQoL in heterogeneous patient populations seeking help at community mental health services. The aims of the study were to compare how HRQoL, measured by the EuroQol five dimensions with five levels (EQ-5D-5L), was distributed compared to other samples from national and international studies, and to explore what factors are associated with HRQoL. METHODS: In a cross-sectional study, 1379 Norwegian outpatients reported their HRQoL before starting treatment. Associations with demographic variables, job status, socio-economic status, and use of pain medication were examined using multiple regression analysis. RESULTS: Most of the sample, 70% to 90%, reported problems with usual activities, pain/discomfort, and anxiety/depression; 30% to 65% reported that these problems were of a moderate to extreme degree. Forty percent reported problems with mobility, and about 20% reported problems with self-care. The sample's HRQoL was considerably lower than the general population, and comparable to patient-groups from specialist mental health services. Originating from a developing country, lower level of education, lower yearly household income, being on sick leave or unemployed, and using pain medication were associated with lower HRQoL. Age, gender, and relationship status were not associated with HRQoL. This is the first study to simultaneously examine the unique contribution of these variables in one study. CONCLUSION: The most impacted domains of HRQoL were pain/discomfort, anxiety/depression, and usual activities. Lower HRQoL was associated with several socio-demographic factors and use of pain medication. These findings might have clinical implications and suggest that mental health professionals should routinely measure HRQoL in addition to symptom severity, to identify areas that should be targeted to improve HRQoL.

Factor structure, measurement invariance, and concurrent validity of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder scale-7 in a Norwegian psychiatric outpatient sample.

OBJECTIVE: The aim of this study was to test factor structure, measurement invariance, and concurrent validity of the nine item Patient Health Questionnaire-9 (PHQ-9) and the seven item Generalized Anxiety Disorder scale-7 (GAD-7) in a heterogeneous outpatient sample. METHOD: Outpatients completed the PHQ-9, GAD-7, and the Working Social Adjustment Scale (WSAS) before starting treatment. Study design was cross-sectional, with convenience sampling. The total sample consisted of 831 participants (61% women). RESULTS: Both PHQ-9 and GAD-7 demonstrated better fit statistics with two-factor and bifactor solutions consisting of a cognitive and somatic factor. Omega hierarchical was .78 for PHQ-9 and .81 for GAD-7. Both instruments achieved scalar invariance across gender, diagnosis, and comorbidity. However, the somatic factors demonstrated poor discriminant validity. These factors are not well separatable and risks being too similar if used together. The general factors of both instruments were most associated with functional impairment, although PHQ-9 demonstrated a stronger association with WSAS (γ = .74, r2 = .62) than GAD-7 (γ = .54, r2 = .32). Using latent mean difference, women and patients with comorbidity had significantly higher scores of both depression and anxiety. CONCLUSION: This study shows that the PHQ-9 and GAD-7 may be used as one-dimensional instruments in clinical settings. Tests for measurement invariance supported that both measures are understood and interpreted comparably across gender and diagnostic subgroups.

Electron Kinetic Entropy across Quasi-Perpendicular Shocks.

We use Magnetospheric Multiscale (MMS) data to study electron kinetic entropy per particle Se across Earth's quasi-perpendicular bow shock. We have selected 22 shock crossings covering a wide range of shock conditions. Measured distribution functions are calibrated and corrected for spacecraft potential, secondary electron contamination, lack of measurements at the lowest energies and electron density measurements based on plasma frequency measurements. All crossings display an increase in electron kinetic entropy across the shock ΔSe being positive or zero within their error margin. There is a strong dependence of ΔSe on the change in electron temperature, ΔTe, and the upstream electron plasma beta, ße. Shocks with large ΔTe have large ΔSe. Shocks with smaller ße are associated with larger ΔSe. We use the values of ΔSe, ΔTe and density change Δne to determine the effective adiabatic index of electrons for each shock crossing. The average effective adiabatic index is ⟨γe⟩=1.64±0.07.

Regulation of integrin α6A by lactogenic hormones in rat pancreatic ß-cells: Implications for the physiological adaptation to pregnancy.

AIM: During pregnancy, the maternal ß-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent ß-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the ß-cell mass during pregnancy in the rat. METHODS: Quantitative RT-PCR was used to evaluate the expression of several integrins and laminins in isolated neonatal rat islets in response to growth hormone (GH) and prolactin (PRL) treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin α6ß1. ß-cell proliferation was evaluated by incorporation of bromodeoxyuridine (BrdU). The role of STAT5 phosphorylation was tested by addition of STAT5 mutants. RESULTS: We found that the mRNA level of integrin-α6A, was upregulated 2.5-fold by PRL or GH. During pregnancy, a biphasic 3.4-4.5-fold increase of integrin-α6A and B mRNA levels was detected. A disintegrin peptide (DP) reduced the hormone-stimulated mitotic activity in neonatal rat ß-cells from 2.9 ± 0.4-fold to 1.3 ± 0.3-fold. The hormone-induced expression of α6ß1 integrin was shown to be mediated via STAT5 as a dominant negative (DN) mutant prevented and a constitutive active (CA) mutant augmented the hGH-stimulated expression. The DP was found to inhibit hGH-induced transactivation of the PRL receptor promoter 1A and reduce the hGH-induced phosphorylation of STAT5. CONCLUSION: These results show that integrin-α6 in ß-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the ß-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes mellitus.

Tissue Thickness Effects on Immunohistochemical Staining Intensity of Markers of Cancer.

High-quality patient samples are required for reliable immunohistochemistry test outcomes that provide a significant benefit for patient care. Among the preanalytic variables in tissue handling, tissue thickness is thought to be easily controlled; however, whether the thickness of the tissue effects the staining intensity for antibody immunohistochemistry has not been quantitatively demonstrated. To investigate, we cut multiblock tissue sections of tonsil, liver, and kidney at 2, 4, 6, and 8 µm thicknesses. Interferometry measurements of the sectioned paraffin showed a <1 µm variation within a preset microtome thickness. Sections were then immunostained with antibodies targeting different cellular localizations; Ki-67 and BCL6 (nuclear), CD7 (membranous), and cytokeratin (cytoplasmic). A pathologist annotated regions of interest for each marker and performed brightfield and whole-slide visual scoring. Then a pixel-wise processing algorithm determined intensity of each pixel in these regions of interest and binned them into predetermined 0, 1+, 2+, or 3+ intensities. Visual scores from brightfield and whole-slide images were highly correlated to the percentage of pixels in each intensity bin. A stepwise increase was observed in pathologist scores and algorithmically defined percentage of pixels in each bin with increasing thickness demonstrating that changes in preset section thickness impacts staining intensity. The use of tissue thickness outside vendors' recommendations might change the intensity including the proportion of positive and negative cells and eventually the overall diagnosis outcome. Therefore, we recommend that tissue be consistently cut within the middle of thickness range specified by the assay manufacturer.

A unipolarly located, cell-surface-associated agglutinin, RapA, belongs to a family of Rhizobium-adhering proteins (Rap) in Rhizobium leguminosarum bv. trifolii.

The phage-display cloning technique was used to find rhizobial proteins that bind to receptors located on the bacterial cell surface. The aim was to clone the gene(s) encoding rhicadhesin, a universal rhizobial adhesion protein, and/or other cell-surface-binding proteins. Four such Rhizobium-adhering proteins (Rap) were revealed in Rhizobium leguminosarum bv. trifolii strain R200. The binding is mediated by homologous Ra domains in these proteins. One member of the Rap protein family, named RapA1, is a secreted calcium-binding protein, which are also properties expected for rhicadhesin. However, the size of the protein (24 kDa instead of 14 kDa) and its distribution among different rhizobia (present in only Rhizobium leguminosarum biovars and R. etli instead of all members of Rhizobiaceae argue against RapA1 being rhicadhesin. Protein RapA1 consists of two homologous Ra domains and agglutinates R200 cells by binding to specific receptors located at one cell pole during exponential growth. Expression of these cell-surface receptors was detected only in rhizobia that produce the RapA proteins. The authors propose that the homologous Ra domains, found to be present also in other proteins with different structure, represent lectin domains, which confer upon these proteins the ability to recognize their cognate carbohydrate structures.

Structural and putative regulatory genes involved in cellulose synthesis in Rhizobium leguminosarum bv. trifolii.

Six genes involved in cellulose synthesis in Rhizobium leguminosarum bv. trifolii were identified using Tn5 mutagenesis. Four of them displayed homology to the previously cloned and sequenced Agrobacterium tumefaciens cellulose genes celA, celB, celC and celE. These genes are organized similarly in R. leguminosarum bv. trifolii. In addition, there were strong indications that two tandemly located genes, celR1 and celR2, probably organized as one operon, are involved in the regulation of cellulose synthesis. The deduced amino acid sequences of these genes displayed a high degree of similarity to the Caulobacter crescentus DivK and PleD proteins that belong to the family of two-component response regulators. This is to our knowledge the first report of genes involved in the regulation of cellulose synthesis. Results from attachment assays and electron microscopic studies indicated that cellulose synthesis in R. leguminosarum bv. trifolii is induced upon close contact with plant roots during the attachment process.

Staphylococcus aureus expresses a cell surface protein that binds both IgG and beta2-glycoprotein I.

The existence of a second IgG-binding protein, protein Sbi, in Staphylococcus aureus has been reported previously. Later data indicated that protein Sbi also bound another serum component. This component has now been affinity-purified on immobilized protein Sbi and identified as beta2-glycoprotein I (beta2-GPI), also known as apolipoprotein H. The minimal beta2-GPI-binding domain was identified by shotgun phage display and the binding was shown to be mediated by a region of 57 amino acids, clearly separated from the IgG-binding domain. It is also shown that protein Sbi, and thus the beta2-GPI-binding activity, is expressed on the staphylococcal cell surface at levels varying between strains.

A second IgG-binding protein in Staphylococcus aureus.

Most strains of Staphylococcus aureus express IgG-binding activity and this binding has been considered to be solely mediated by protein A. However, the existence of a second gene in S. aureus strain 8325-4 encoding an IgG-binding polypeptide was recently reported. This novel IgG-binding polypeptide was found after panning a shotgun phage display library, made from chromosomal DNA, against immobilized human IgG. The complete gene (sbi) encoding this novel IgG-binding protein, denoted protein Sbi, has now been cloned and sequenced. Analysis of other S. aureus strains showed that this gene is not unique for strain 8325-4. The protein consists of 436 amino acids and exhibits an immunoglobulin-binding specificity similar to protein A. Furthermore, it is shown that Sbi is highly expressed in strain Newman 4, which shows that IgG-binding activity in S. aureus can be mediated by proteins other than protein A.