Examining the impact of substance use on hospital length of stay in schizophrenia spectrum disorder: a retrospective analysis.

BACKGROUND: Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease, adherence to therapeutic regimens, treatment outcomes, duration of hospital stays, and the frequency of hospitalizations. The primary objective of the present study is to investigate the relationship between comorbid substance use disorders, antipsychotic treatment, and the length of stay in individuals hospitalized for treatment of schizophrenia. METHODS: We conducted a retrospective analysis of electronic health records spanning a 12-month period, specifically focusing on adult patients diagnosed with schizophrenia who were discharged from the University Hospital of Psychiatry Zurich between January and December 2019. We documented the number and types of diagnosed substance use disorder, the antipsychotic treatment, the length of stay, and the number of previous hospitalizations for each patient. RESULTS: Over a third (n = 328; 37.1%) of patients with schizophrenia had comorbid substance use with cannabis being the most frequent consumed substance. Patients with substance use (either single or multiple) were more frequently hospitalized; those with multiple substance use more frequently than those with a single substance use (F(2, 882) = 69.06; p < 0.001). There were no differences regarding the rate of compulsory admission. Patients with no substance use had a lower HoNOS score at discharge (F(2, 882) = 4.06). Patients with multiple substance use had a shorter length of stay (F(2, 882) = 9.22; p < 0.001), even after adjusting for duration of illness, previous hospitalizations, diagnosis, and antipsychotic treatment. CONCLUSIONS: In patients with schizophrenia, comorbid single or multiple substance use has a relevant negative impact on treatment and thus on the course of disease. Substance use in patients with schizophrenia should therefore receive special attention in order to reduce re-hospitalization rates and improve the clinical outcome.

Predictors for early and long-term readmission in involuntarily admitted patients.

BACKGROUND: It is a common aim to reduce psychiatric readmissions. Although risk factors for readmissions were described, specific data in the group of patients with potentially aversively experienced involuntary admissions are lacking. To better understand underlying mechanisms, it is important to identify factors that are linked to readmissions in this specific patient group, which is the purpose of the current paper. METHODS: A four-year cohort of N = 3575 involuntary admissions (IA) was followed-up for subsequent re-hospitalization. Demographic, administrative and clinical factors associated with short- (within 30 days) or long-term (> 30 days) readmissions were examined using logistic regression modelling. RESULTS: Almost half of all IA cases were readmitted within the observation period, whereof every fifth readmission was within the first month after discharge from the involuntary index hospitalization. Adjusted regression modelling revealed problematic substance use at admission and assisted living or homelessness as risk factors for readmission, while high functioning at discharge, anxiety disorders, no subsequent treatment after discharge or IA due to danger to others were negatively associated with readmission. Factors specifically linked to short-term readmission were substance use and personality disorders, abscondence or discharge by initiation of the clinic, as well as being discharged to any place except the patient's home. There were no specific risk-factors for long-term readmission. CONCLUSIONS: To prevent readmissions after IA, especially for patients at risk, the aim of treatment strategies should be to focus on intensive discharge planning, enable continuous treatment in the outpatient setting, and provide social support.

Impact of psychopathology on day-to-day living in patients with schizophrenia: A network analysis.

Although the relationship between schizophrenia and disability is well established, the association between the symptoms of the disorder and functional domains remains unclear. The current study explored the nuances of the relationship between symptoms and domains of functioning in a sample of 1127 patients with schizophrenia. We assessed the symptoms of schizophrenia with the Positive and Negative Syndrome Scale (PANSS) and psychosocial functioning with the mini-ICF-APP (mini-International Classification of Functioning Rating for Limitations of Activities and Participation in Psychological Disorders). The mean PANSS score was 94.28 (27.20), and the mean mini-ICF-APP score was 25.25 (8.96), both of which are indicative of severe symptom load and impairment. We were able to show a strong relationship and overlap between symptoms and disability in patients with schizophrenia. We identified several symptoms related to functional impairment. Deficits in judgment and abstract thinking contribute to impairment through poor adherence (to routines and compliance with rules) and difficulties in planning and organizing. We believe that in schizophrenia, symptoms and their interactions constitute a disorder beyond any single manifestation. Furthermore, we suggest that cognitive testing and cognitive treatment should become part of the standard of care for patients with schizophrenia.

Relationship between antipsychotic medication and aggressive events in patients with a psychotic disorder hospitalized for treatment.

BACKGROUND: Disruptive and aggressive behavior is frequent in patients with a psychotic disorder; furthermore, it is a recurrent reason for compulsory admission. Even during treatment, many patients continue to show aggressive behavior. Antipsychotic medication is posed to have anti-aggressive properties; its prescription is a common strategy for the treatment (and prevention) of violent behavior. The present study aims to investigate the relation between the antipsychotic class, according to the dopamine D2-Receptor binding affinity (i.e., "loose" - "tight binding"), and aggressive events perpetrated by hospitalized patients with a psychotic disorder. METHODS: We conducted a four-year retrospective analysis of legally liable aggressive incidents perpetrated by patients during hospitalization. We extracted patients' basic demographic and clinical data from electronic health records. We used the Staff Observation Aggression Scale (SOAS-R) to grade the severity of an event. Differences between patients with a "loose" or "tight-binding" antipsychotic were analyzed. RESULTS: In the observation period, there were 17,901 direct admissions; and 61 severe aggressive events (an incidence of 0.85 for every 1,000 admissions year). Patients with a psychotic disorder perpetrated 51 events (incidence of 2.90 for every 1,000 admission year), with an OR of 15.85 (CI: 8.04-31.25) compared to non-psychotic patients. We could identify 46 events conducted by patients with a psychotic disorder under medication. The mean SOAS-R total score was 17.02 (2.74). The majority of victims in the "loose-binding" group were staff members (73.1%, n = 19), while the majority of victims in the "tight-binding" group were fellow patients (65.0%, n = 13); (X2(3,46) = 19.687; p < 0.001). There were no demographic or clinical differences between the groups and no differences regarding dose equivalents or other prescribed medication. CONCLUSIONS: In aggressive behaviors conducted by patients with a psychotic disorder under antipsychotic medication, the dopamine D2-Receptor affinity seems to have a high impact on the target of aggression. However, more studies are needed to investigate the anti-aggressive effects of individual antipsychotic agents.

Impact of language proficiency on mental health service use, treatment and outcomes: "Lost in Translation".

BACKGROUND: Mastery of a language is bound to place of origin; low language proficiency is thus related to migration and cultural differences, all of which influence access to mental health care, treatment and outcomes. Switzerland, being multilingual, allows the disentangling of language proficiency from migration and, to some extent, culture. This study uses propensity score matching to explore how language proficiency relates to help-seeking behaviour, service use, treatment and outcomes in patients with mental health disorders. METHODS: We used the first admission of patients admitted to and discharged from an academic psychiatric hospital in Switzerland between January 1st, 2013 and December 31st, 2019, with an observation period of one-year post-discharge (until December 31st, 2020). We paired 2101 patients with low language proficiency to 2101 language proficient patients, balancing baseline sociodemographic and clinical characteristics using propensity score matching. RESULTS: Patients with low language proficiency had a higher probability of compulsory admission (OR: 1.79, 99%CI: 1.60-2.02); which remained after adjustment for confounders (OR: 1.51; 99%CI: 1.21-1.89). Whilst in treatment, they had higher rates of compulsory medication (OR: 1.73, 99%CI: 1.16-2.59) and seclusion/restraint (OR: 1.87, 99%CI: 1.25-2.79). Furthermore, patients initially admitted voluntarily had a higher probability of being compulsorily retained (OR: 1.74, 99%CI: 1.24-2.46). Both groups showed similar clinical improvement rates and service use parameters. CONCLUSIONS: Our results demonstrate that low language proficiency constitutes a risk factor for coercive measures throughout hospitalisation. The results demonstrate the need for an increase in language sensitivity in psychiatric care.

Patients' experiences and satisfaction with home treatment for acute mental illness: a mixed-methods retrospective study.

BACKGROUND: Home treatment (HT) has been proposed as a patient-centred alternative to acute mental inpatient care although evidence of patient-reported outcomes has remained limited. AIMS: The aim of this study was to examine patient experiences and satisfaction with HT. METHODS: This retrospective mixed-methods study included telephone interviews of 159 patients receiving HT between 2016 and 2019. Associations between patients' characteristics and global satisfaction (ZUF-8 scale) were assessed. Differences between HT patients and inpatients were tested on a propensity score -matched inpatient sample. Qualitative analyses were conducted using thematic analysis. RESULTS: Global satisfaction with HT was slightly higher than in the inpatient sample (p = 0.019). There was no relationship between satisfaction and patients' characteristics, such as gender, age, main psychiatric diagnosis, and treatment duration, but satisfaction was higher for patients who perceived HT as their only treatment option. Participants particularly appreciated the person-centred care and practical support whereas staff continuity and medical treatment were main sources of dissatisfaction. CONCLUSION: The results indicate that HT seems to be a more patient-centred alternative to inpatient treatment and might close a gap in the psychiatric care of patients who preferred not to use inpatient services but needed higher treatment intensity than outpatient treatment.

Validation of Visual and Auditory Digital Markers of Suicidality in Acutely Suicidal Psychiatric Inpatients: Proof-of-Concept Study.

BACKGROUND: Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. OBJECTIVE: We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. METHODS: We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. RESULTS: Suicide severity was associated with multiple visual and auditory markers, including speech prevalence (ß=-0.68, P=.02, r2=0.40), overall expressivity (ß=-0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (ß=-1.24, P=.006, r2=0.48) and head yaw variability (ß=-0.54, P=.06, r2=0.32). CONCLUSIONS: Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

Hypoxia and the Receptor for Advanced Glycation End Products (RAGE) Signaling in Cancer.

Hypoxia is characterized by an inadequate supply of oxygen to tissues, and hypoxic regions are commonly found in solid tumors. The cellular response to hypoxic conditions is mediated through the activation of hypoxia-inducible factors (HIFs) that control the expression of a large number of target genes. Recent studies have shown that the receptor for advanced glycation end products (RAGE) participates in hypoxia-dependent cellular adaptation. We review recent evidence on the role of RAGE signaling in tumor biology under hypoxic conditions.

Home Treatment for Acute Mental Healthcare: Who Benefits Most?

Home treatment (HT) has been proposed as an alternative to inpatient treatment for individuals in acute mental crises. However, there is limited evidence concerning the effectiveness of HT to date. The aim of this study was to investigate which patients benefit most from HT. The concept and utilization of two HT services in Switzerland were retrospectively compared based on routine medical data of all patients who were treated in one of the two HT services between July 2016 and December 2017. We examined which patient characteristics were related to successful replacement of hospital care by HT based on a calculated success score using binary regression analyses. The whole sample included 408 individuals with an average age of 43 years and of whom 68% were female. As a result of conceptual similarities, in both HT settings, the typical patient was middle-aged, female and having an affective disorder as the main diagnosis. Half of the treatment cases met the criteria of successful replacement of hospital care (> 50% of the total treatment episodes in HT, treatment duration < 40 days and treatment terminated by mutual agreement). The results of the regression analyses indicated that patients with a lower symptom severity at admission (lower HoNOS score) and those who were employed had more likely a successful replacement of hospital care.The findings suggest that patients with acute mental disorders who have a certain level of functioning and social support might benefit most from HT in the sense of successful replacement of hospital care.

Assessing the severity of psychiatric disorders using the Health of the Nation Outcome Scales: An equipercentile linking analysis.

OBJECTIVE: The Health of the Nation Outcome Scales was developed as an overall measure of mental health, applicable to the complete range of psychiatric disorders. Meanwhile, it is a benchmark tool for service providers and is also used for the allocation of costs and funding. The ability of the Health of the Nation Outcome Scales to assess and differentiate the severity of psychiatric disorders is largely unknown, as it is the interpretation of a change in score. We aim to establish Health of the Nation Outcome Scales cut-off and benchmark values for severity and improvement - respectively change, using equipercentile linking to the Clinical Global Impression scales. METHODS: In a clinical sample of 30,616 individuals with a psychiatric disorder, we used a multivariate regression analysis to determine the correlation between the scales and possible confounders. We used an equipercentile linking analysis of the Clinical Global Impressions severity scale with the Health of the Nation Outcome Scales sum score to establish cut-off values for severity. The linking of the Health of the Nation Outcome Scales sum score difference and the percentage of change to the Clinical Global Impression improvement scale determined benchmark values for change (i.e. improvement or deterioration). RESULTS: The Health of the Nation Outcome Scales and Clinical Global Impression scales showed a Spearman correlation of 0.38 (p < 0.000). Clinical Global Impression-Severity: 'borderline-ill' corresponded to Health of the Nation Outcome Scales score 3-5; 'mildly ill' to 6-10; 'moderately ill' to 11-16; 'markedly ill' to 17-25; 'severely ill' to 26-35; and 'extremely ill' to a score ⩾36. The Spearman correlation between the percentage change of the Health of the Nation Outcome Scales was 0.39 (p > 0.000); Clinical Global Impression-Improvement: 'minimally improved' corresponded to Health of the Nation Outcome Scales reduction of 4 points or 9%; 'much-improved' to 12 points or 48%; 'very-much-improved' to ⩾20 points or ⩾90%. Clinical Global Impression-Improvement: 'minimally worse' corresponded to an increase of 6 points or 25%; 'much-worse' to 12 points or 54%; and finally, 'very-much-worse' to >18 points or ⩾82%. CONCLUSION: Our results allow for the comparison of severity and response to treatment of patients with a psychiatric disorder, independent of diagnosis.

RAGE Signaling in Melanoma Tumors.

Despite recent progresses in its treatment, malignant cutaneous melanoma remains a cancer with very poor prognosis. Emerging evidences suggest that the receptor for advance glycation end products (RAGE) plays a key role in melanoma progression through its activation in both cancer and stromal cells. In tumors, RAGE activation is fueled by numerous ligands, S100B and HMGB1 being the most notable, but the role of many other ligands is not well understood and should not be underappreciated. Here, we provide a review of the current role of RAGE in melanoma and conclude that targeting RAGE in melanoma could be an approach to improve the outcomes of melanoma patients.

RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells.

The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and ß1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT.

Assessing the severity of functional impairment of psychiatric disorders: equipercentile linking the mini-ICF-APP and CGI.

BACKGROUND: The assessment of functioning and impairment due to psychiatric illness has been acknowledged to be crucial for research and practice. This led to the development of the mini-ICF-APP, which provides a reliable and time-efficient measure of functioning and impairment. Although its use is increasing, it remains unclear how it reflects severity and how change might be interpreted from a clinical perspective. METHODS: In a clinical sample of 3067 individuals hospitalized for mental health treatment, we used an equipercentile approach to link the mini-ICF-APP with the Clinical Global Impression scale (CGI) at admission and discharge. We linked the mini-ICF-APP sum score to the CGI-S scale and the mini-ICF-APP proportional change between admission and discharge to the CGI-I scale. RESULTS: The mini-ICF-APP and CGI scales showed a Spearman correlation of 0.50 (p < .000). CGI-S: "borderline-ill" corresponded to a mini-ICF-APP score 1-2; "mildly-ill" to 3-7; "moderately-ill" to 8-15; "markedly-ill" to 16-24; "severely-ill" to 25-37; and "extremely-ill" to a score ≥ 38. The Spearman correlation between the percentage change of mini-ICF-APP sum score and the CGI-I was 0.32 (p > .000); "no-change" in the CGI-I corresponded to an increase or decrease of 2%; "minimally-improved" to a mini-ICF-APP reduction of 3-30%; "much-improved" to a reduction of 31-63%; "very-much-improved" to a reduction of ≥64% "minimally-worse" to an increase of 3-34% "much-worse" to an increase of 35-67%; and finally "very-much-worse" with an increase of ≥68%. CONCLUSIONS: Our findings improve understanding of the clinical meaning of the mini-ICF-APP sum score and percentage change in patients hospitalized for treatment.

More Optimistic Recovery Attitudes Are Associated with Less Stigmatization of People with Mental Illness among Healthcare Professionals Working on Acute and Semi-Acute Psychiatric Wards.

Stigmatization towards individuals with mental illness is common among mental healthcare professionals, yet poses a key concern regarding the provision of effective support and therapy for those undergoing psychiatric treatment. In this study, we examined to what extent recovery attitudes among mental healthcare professionals are associated with stigmatization. We conducted a survey among staff members (n = 110) of a large psychiatric hospital working on acute or semi-acute wards one year following a multi-professional training session, which included the promotion of recovery orientation as a therapeutic approach. The survey included measures such as gender, age, professional background, years of working experience, ward setting (mostly open or closed doors), recovery attitudes (RAQ-7), and stigmatization of individuals with mental illness (OMS-HC scale). Mental healthcare professionals who attended training in recovery orientation significantly more frequently stated to know the concept of recovery compared to those who did not receive training. In addition, recovery attitudes were more optimistic and significantly associated with levels of stigmatization among professionals who were familiar with the concept of recovery. Despite the cross-sectional study design that did not test causal links, these findings suggest that enhancing recovery attitudes through training may lead to less stigmatization among mental healthcare professionals.

Self-stigma as a barrier to recovery: a longitudinal study.

Stigma limits life opportunities of persons with mental illness. Self-stigma, the internalization of negative stereotypes, undermines empowerment and could hinder recovery. Here we examined self-stigma's effect on recovery among 222 disability pensioners with mental illness over 2 years, controlling for age, gender, symptoms and recovery at baseline measured by the Recovery Assessment Scale. More self-stigma at baseline was associated with a significant decrease in recovery after 1 year (not significant after 2 years). An increase of self-stigma from baseline to follow-up predicted less recovery 1 and 2 years later. Interventions that reduce self-stigma could therefore improve recovery.

Involuntary hospitalization, stigma stress and suicidality: a longitudinal study.

People with severe mental illness and a history of involuntary hospitalization may experience stigma-related stress and suffer negative consequences as a result. However, the long-term impact of stigma stress on suicidality in this population remains unknown. This longitudinal study therefore examined stigma stress, self-stigma, self-esteem and suicidal ideation among 186 individuals with mental illness and recent involuntary hospitalization. After adjusting for age, gender, diagnoses and symptoms, more stigma stress at baseline predicted suicidal ideation after 2 years, mediated by increased self-stigma and decreased self-esteem after 1 year. Anti-stigma interventions that reduce stigma stress and self-stigma could therefore support suicide prevention.

The role of S100 proteins and their receptor RAGE in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with low survival rates. Current therapeutic treatments have very poor response rates due to the high inherent chemoresistance of the pancreatic-cancer cells. Recent studies have suggested that the receptor for advanced glycation end products (RAGE) and its S100 protein ligands play important roles in the progression of PDAC. We will discuss the potential role of S100 proteins and their receptor, RAGE, in the development and progression of pancreatic cancer.

Determinants of cerebral hemodynamics during the Trail Making Test in schizophrenia.

Patients with schizophrenia show deficits in cognitive functioning, and studies on cerebral hemodynamics have revealed aberrant patterns of mean cerebral blood flow velocity (MFV), an equivalent of cerebral blood flow (CBF). Therefore, we carried out a controlled study that assessed MFV in schizophrenia during a well-known neuropsychological task, the Trail Making Test (TMT). We measured MFV in the middle cerebral arteries using functional transcranial Doppler sonography in 15 schizophrenia patients and 15 healthy subjects. In comparison to healthy subjects, patients performed poorer on the TMT-A and the TMT-B, and there was increased cerebral blood flow velocity during the TMT-B. A comparison of subgroups of patients and controls matched in performance on the TMT-B revealed that these patients still showed significantly increased cerebral blood flow velocity. Increased MFV in schizophrenia suggests specific alterations of cerebral hemodynamics during the Trail Making Test, Part B, which are not detectable during visuomotor activity, and which are independent of performance. These findings emphasize the pathophysiological importance of cognitive functioning in schizophrenia, but cast doubts whether performance in this particular test plays a relevant role for CBF abnormalities in schizophrenia.

RAGE overexpression confers a metastatic phenotype to the WM115 human primary melanoma cell line.

The formation of melanoma metastases from primary tumor cells is a complex phenomenon that involves the regulation of multiple genes. We have previously shown that the receptor for advanced glycation end products (RAGE) was up-regulated in late metastatic stages of melanoma patient samples and we hypothesized that up-regulation of RAGE in cells forming a primary melanoma tumor could contribute to the metastatic switch of these cells. To test our hypothesis, we overexpressed RAGE in the WM115 human melanoma cell line that was established from a primary melanoma tumor of a patient. We show here that overexpression of RAGE in these cells is associated with mesenchymal-like morphologies of the cells. These cells demonstrate higher migration abilities and reduced proliferation properties, suggesting that the cells have switched to a metastatic phenotype. At the molecular level, we show that RAGE overexpression is associated with the up-regulation of the RAGE ligand S100B and the down-regulation of p53, ERK1/2, cyclin E and NF-kB. Our study supports a role of RAGE in the metastatic switch of melanoma cells.

Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex.

S100B is a damage-associated molecular pattern protein that, when released into the extracellular milieu, triggers initiation of the inflammatory response through the receptor for advanced glycation end products (RAGE). Recognition of S100B is accomplished via the amino-terminal variable immunoglobulin domain (V-domain) of RAGE. To gain insights into this interaction, a complex between S100B and a 15-amino-acid peptide derived from residues 54-68 of the V-domain was crystallized. The X-ray crystal structure was solved to 2.55 Å resolution. There are two dimers of S100B and one peptide in the asymmetric unit. The binding interface of this peptide is compared with that found in the complex between S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals that although the peptides adopt completely different backbone structures, the residues buried at the interface interact with S100B in similar regions to form stable complexes. The binding affinities of S100B for the intact wild-type V-domain and a W61A V-domain mutant were determined to be 2.7 ± 0.5 and 1.3 ± 0.7 µM, respectively, using fluorescence titration experiments. These observations lead to a model whereby conformational flexibility in the RAGE receptor allows the adoption of a binding conformation for interaction with the stable hydrophobic groove on the surface of S100B.