Flexible Assertive Community Treatment, Severity of Symptoms and Psychiatric Health Service Use, a Real life Observational Study

BACKGROUND: Introduction of Flexible Assertive Community Treatment (FACT) may be associated with increased remission rates and changes in patterns of care. The present paper reports on differences in psychosocial functioning and health care use between patients in FACT and two groups of patients not currently provided with a specific model of community service. METHODS: The ongoing "Pharmacotherapy Monitoring and Outcome Survey" provided routine outcome measures of patients using antipsychotics in the north of the Netherlands. Level of psychosocial functioning was assessed using the Health of the Nations Outcome Scales (HoNOS) and matched with psychiatric health care consumption obtained from the Psychiatric Case Register. Patients who never received FACT, patients ever in FACT but not at assessment date, and patients in FACT were identified. Data were subjected to multilevel linear regression analysis. RESULTS: Data showed that most patients in FACT also had non-FACT episodes after the start of FACT. Furthermore, patients in FACT displayed higher levels of psychosocial functioning and used more outpatient care than the other two groups. CONCLUSIONS: Patients in FACT receive more outpatient care and have better psychosocial functioning. However, causal inferences cannot be derived from these data. In addition, membership of a FACT-team in this setting did not last indefinitely

Sensitivity to change of the Beck Depression Inventory versus the Inventory of Depressive Symptoms

Background: In a previous study which made a comparison between disorder-specific and generic instruments to assess outcome of treatments for depression, the Beck Depression Inventory, Second Edition (BDI-II) seemed to be more sensitive to change than the Inventory of Depressive Symptoms- Self Rating (IDS-SR). Methods: A set with longitudinal data from Routine Outcome Monitoring (n=144) were analyzed with multilevel models with random intercepts. The sensitivity to change of two disorder-specific instruments, the BDI-II and the IDS-SR, were compared head to head. Results: The BDI-II was more sensitive to change when measuring treatment outcome compared to the IDS-SR. The BDI-II decreases significantly more over time than the IDS-SR: the average decrease per week for the IDS-SR is -.012 (95%CI -0.015, -0.009) and for the BDI-II it is -.017 (95%CI -0.021, -0.014). Limitations: Conclusions can only be preliminary due to a small sample size. Conclusions: Treatment outcomes measured with questionnaires may differ depending on the degree of sensitivity to change of the instruments

Treponema denticola Major Outer Sheath Protein Induces Actin Assembly at Free Barbed Ends by a PIP2-Dependent Uncapping Mechanism in Fibroblasts

The major outer sheath protein (Msp) of Treponema denticola perturbs actin dynamics in fibroblasts by inducing actin reorganization, including subcortical actin filament assembly, leading to defective calcium flux, diminished integrin engagement of collagen, and retarded cell migration. Yet, its mechanisms of action are unknown. We challenged Rat-2 fibroblasts with enriched native Msp. Msp activated the small GTPases Rac1, RhoA and Ras, but not Cdc42, yet only Rac1 localized to areas of actin rearrangement. We used Rac1 dominant negative transfection and chemical inhibition of phosphatidylinositol-3 kinase (PI3K) to show that even though Rac1 activation was PI3K-dependent, neither was required for Msp-induced actin rearrangement. Actin free barbed end formation (FBE) by Msp was also PI3K-independent. Immunoblotting experiments showed that gelsolin and CapZ were released from actin filaments, whereas cofilin remained in an inactive state. Msp induced phosphatidylinositol (4,5)-bisphosphate (PIP2) formation through activation of a phosphoinositide 3-phosphatase and its recruitment to areas of actin assembly at the plasma membrane. Using a PIP2 binding peptide or lipid phosphatase inhibitor, PIP2 was shown to be required for Msp-mediated actin uncapping and FBE formation. Evidently, Msp induces actin assembly in fibroblasts by production and recruitment of PIP2 and release of the capping proteins CapZ and gelsolin from actin barbed ends

Life years lost for users of specialized mental healthcare

Background: Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder.Methods: Mortality and basic demographics were available for a population of N = 10,914 SMH users in the north of The Netherlands from 2010 until 2017. To estimate mortality over the adult lifespan, parametric Gompertz distributions were fitted on observed mortality using interval regression. Life years lost were computed by calculating the difference between integrals of the survival functions for the general population and the study sample, thus correcting for age. Survival for the general population was obtained from Statistics Netherlands (CBS).Results: SMH users were estimated to lose 9.5 life years (95% CI: 9.4–9.6). Every major diagnosis category was associated with a significant loss of life years, ranging from 7.2 (95% CI: 6.4–7.9) years for anxiety patients to 11.7 (95% CI: 11.0–12.5) years for bipolar disorder patients. Significant differences in mortality were observed between male SMH users and female SMH users, with men losing relatively more life years: 11.0 (95% CI: 10.9–11.2) versus 8.3 (95% CI: 8.2–8.4) respectively. This difference was also observed between sexes within every diagnosis, although the difference was insignificant for bipolar disorder. Conclusion: There were significant differences in mortality between SMH users and the general population. Substantial differences were observed between sexes and between diagnoses. Additional attention is required, and possibly specific interventions are needed to reduce the amount of life years lost by SMH users.</p

Real-World Treatment Costs and Care Utilization in Patients with Major Depressive Disorder With and Without Psychiatric Comorbidities in Specialist Mental Healthcare

BACKGROUND: The majority of patients with major depressive disorder (MDD) have comorbid mental conditions. OBJECTIVES: Since most cost-of-illness studies correct for comorbidity, this study focuses on mental healthcare utilization and treatment costs in patients with MDD including psychiatric comorbidities in specialist mental healthcare, particularly patients with a comorbid personality disorder (PD). METHODS: The Psychiatric Case Register North Netherlands contains administrative data of specialist mental healthcare providers. Treatment episodes were identified from uninterrupted healthcare use. Costs were calculated by multiplying care utilization with unit prices (price level year: 2018). Using generalized linear models, cost drivers were investigated for the entire cohort. RESULTS: A total of 34,713 patients had MDD as a primary diagnosis over the period 2000–2012. The number of patients with psychiatric comorbidities was 24,888 (71.7%), including 13,798 with PD. Costs were highly skewed, with an average ± standard deviation cost per treatment episode of €21,186 ± 74,192 (median €2320). Major cost drivers were inpatient days and daycare days (50 and 28% of total costs), occurring in 12.7 and 12.5% of episodes, respectively. Compared with patients with MDD only (€11,612), costs of patients with additional PD and with or without other comorbidities were, respectively, 2.71 (p < .001) and 2.06 (p < .001) times higher and were 1.36 (p < .001) times higher in patients with MDD and comorbidities other than PD. Other cost drivers were age, calendar year, and first episodes. CONCLUSIONS: Psychiatric comorbidities (especially PD) in addition to age and first episodes drive costs in patients with MDD. Knowledge of cost drivers may help in the development of future stratified disease management programs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40273-021-01012-x

Characterization of iodothyronine sulfotransferase activity in rat liver

Sulfation is an important pathway in the metabolism of thyroid hormone because it strongly facilitates the degradation of the hormone by the type I iodothyronine deiodinase. However, little is known about the properties and possible regulation of the sulfotransferase(s) involved in the sulfation of thyroid hormone. We have developed a convenient method for the analysis of iodothyronine sulfotransferase activity in tissue cytosolic fractions, using radioiodinated 3,3'-diiodothyronine (3,3'-T2) as the preferred substrate, unlabeled 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as the sulfate donor, and Sephadex LH-20 minicolomns for separation of the products. We found that iodothyronine sulfotransferase activity in rat liver cytosol is 1) higher in male than in female rats; 2) optimal at pH 8.0; 3) characterized (at 50 microM PAPS and pH 7.2) by apparent Michaelis-Menton (Km) values for 3,3'-T2 of 1.77 and 4.19 microM, and Vmax values of 1.94 and 1.45 nmol/min per mg protein in male and female rats, respectively; 4) characterized (at 1 microM 3,3'-T2 and pH 7.2) by apparent Km values for PAPS of 4.92 and 3.80 microM and Vmax values of 0.72 and 0.31 nmol/min per mg protein, in males and females, respectively; 5) little affected by hyperthyroidism in both male and female rats, but significantly decreased by hypothyroidism in males but not in females; and 6) not affected by short-term (3 days) fasting in both male and female rats, but significantly decreased by long-term (3 weeks) food restriction to one-third of normal intake in males but not in females. It is suggested that the higher hepatic iodothyronine sulfotransferase activity in male vs. female rats, as well as the decreases induced in males by hypothyroidism and long-term food restriction, represents differences in the expression of the male-dominant isoenzyme rSULT1C1

Mental health care use in adolescents with and without mental disorders

The aim of the study was to estimate the proportion of adolescents with and without a psychiatric diagnosis receiving specialist mental health care and investigate their problem levels as well as utilization of other types of mental health care to detect possible over-and under-treatment. Care utilization data were linked to psychiatric diagnostic data of 2230 adolescents participating in the TRAILS cohort study, who were assessed biannually starting at age 11. Psychiatric diagnoses were established at the fourth wave by the Composite International Diagnostic Interview. Self-, parent-and teacher-reported emotional and behavioral problems and self-reported mental health care use were assessed at all four waves. Of all diagnosed adolescents, 35.3 % received specialist mental health care. This rate increased to 54.5 % when three or more disorders were diagnosed. Almost a third (28.5 %) of specialist care users had no psychiatric diagnosis; teachers gave them relatively high ratings on attention and impulsivity subscales. Diagnosed adolescents without specialist mental health care also reported low rates of other care use. We found no indication of overtreatment. Half of the adolescents with three or more disorders do not receive specialist mental health care nor any other type of care, which might indicate unmet needs

Оптимізація взаємодії промислових підприємств з інститутами інноваційної інфраструктури

У статті розглянуто основні проблеми взаємодії промислових підприємств з інститутами інноваційної інфраструктури в Україні та запропоновано деякі заходи по їх вирішенню.В статье рассмотрены основные проблемы взаимодействия промышленных предприятий с институтами инновационной инфраструктуры в Украине и предложены некоторые меры по их разрешению.In this article the main problems of interaction of industrial enterprises with institutions of innovative infrastructure in Ukraine and certain ways for their solving are proposed

Thyroid function and deiodinase activities in rats with marginal iodine deficiency

The hypothesis tested was whether marginal iodine deficiency for a period of 6 wk affects iodothyronine deiodinase activities in liver and brain of rats. Male rats were fed purified diets either deficient or sufficient in iodine; the diets were fed on a restricted basis (60% of ad libitum intake). Body weight gain of the two groups was comparable. Iodine deficiency was evidenced by increased thyroid weight (26%), reduced urinary iodine excretion (80%), and reduced plasma T4 concentrations (22%). Activities of liver type I and brain type III deiodinase were unchanged, but the activity of type II deiodinase in brain was increased (28%) in the iodine-deficient rats. Food restriction per se significantly lowered T3 (30%) and T4 (22%) concentrations in plasma and decreased type III deiodinase activity in brain (30%). These results indicate that in marginal iodine deficiency the activities of hepatic type I deiodinase and brain type III deiodinase are unchanged, whereas that of brain type II deiodinase is increased