The LIVER CARE trial - screening for liver disease in individuals attending treatment for alcohol use disorder: a randomized controlled feasibility trial.

BACKGROUND: Alcohol-related liver disease is a preventable disease with high mortality. If individuals with alcohol-related liver disease were to be diagnosed earlier by screening and they reduced their alcohol consumption, lives lost to alcohol-related liver disease might be saved. A liver stiffness measurement (FibroScan©) is a key tool to screen for alcohol-related liver disease in asymptomatic individuals. No randomized controlled trials have been conducted to test if screening for liver disease reduces alcohol consumption in individuals with alcohol use disorders, in addition to what can be obtained by motivational interventions. We aimed to assess the feasibility of a randomized controlled trial of a screening for liver disease on the prevalence of alcohol abstinence or light consumption after 6 months in individuals attending outpatient treatment for alcohol use disorder. METHODS: We used an interdisciplinary approach to develop the format of the randomized controlled trial. Individuals were recruited from one outpatient treatment facility for alcohol use disorders. Study participants were randomized 1:1 to receive a) a liver stiffness measurement in addition to usual care (intervention) or b) usual care (control). Follow-up on alcohol consumption was assessed by telephone interview after 6 months and corroborated by data from records from public hospitals and the alcohol treatment facility. Feasibility was assessed by probabilities of recruitment, retention, and completion and estimated by the exact binominal test, with success defined as > 50% participation for each endpoint. The study design was evaluated at interdisciplinary meetings with staff and researchers from the outpatient alcohol treatment facility and the hospital clinic. RESULTS: Forty of 57 invited individuals agreed to participate in the study (recruitment = 70% (95% CI: 57-82)); 19 of 20 participants randomized to the intervention showed up for the screening (retention = 95% (95% CI: 75-100)). Follow-up telephone interviews succeeded for 33 of 39 reachable participants (completion = 85% (95% CI: 69-94)). Treatment records indicated that the 6 participants who were lost to follow-up for the telephone interview had not achieved alcohol abstinence or light consumption. There was no evidence that the intervention increased abstinence or light alcohol consumption at follow-up: 45% (95% CI: 23-68) in the intervention group and 65% (95% CI: 41-85) in the control group had a alcohol consumption below 10 standard drinks/week at 6 months. The main obstacle regarding study feasibility was to avoid disappointment in individuals randomized as controls. CONCLUSIONS: This feasibility study developed a study design to test the influence of screening for liver disease on abstinence or light alcohol consumption in individuals attending treatment for alcohol use disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05244720; registered on February 17, 2022.

Virtual reality-assisted cognitive behavioral therapy for patients with alcohol use disorder: a randomized feasibility study.

Introduction: Cognitive behavioral therapy (CBT) is an evidence-based treatment for alcohol use disorder (AUD). Exposure to high-risk situations in virtual reality (VR) has been suggested to have a potential therapeutical benefit, but no previous study has combined VR and CBT for AUD. We aimed to investigate the feasibility of using VR-simulated high-risk environments in CBT-based treatment of AUD. Methods: We randomized ten treatment-seeking AUD-diagnosed individuals to three sessions of conventional CBT or VR-assisted CBT performed at two outpatient clinics in Denmark. In each session, patients randomized to VR-CBT were exposed to VR-simulations from a restaurant to induce authentic thoughts, emotions, physiological reactions, and craving for CBT purposes. The primary outcome measure was feasibility: Drop-out rate, psychological reactions, and simulator sickness. Secondary outcomes were assessment of preliminary short-term changes in alcohol consumption and craving from baseline to one-week and one-month follow-up. In addition, the study was conducted for training in operationalization of VR equipment, treatment manuals, and research questionnaires. Results: The majority of patients completed all study visits (90%). VR induced authentic high-risk related thoughts, emotions, and physiological reactions that were considered relevant for CBT by patients and therapists. Four of five patients randomized to VR-CBT experienced cravings during VR simulations, and most of these patients (3/5) experienced mild simulator sickness during VR exposure. The preliminary data showed that patients receiving VR-CBT had more reduction in alcohol consumption than patients receiving conventional CBT at one week- (median 94% vs. 72%) and one-month follow-up (median 98% vs. 55%). Similar results were found regarding changes in cravings. Conclusion: We demonstrated VR-CBT to be a feasible intervention for patients with AUD which supports continued investigations in a larger randomized clinical trial evaluating the efficacy of VR-CBT. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT04990765?cond=addiction%20CRAVR&rank=2, identifier NCT05042180.

Perceived advantages and disadvantages of substance use in a dual diagnosis population with severe mental disorders and severe substance use disorder. Considering the self-medication hypothesis.

AIM: Based on a large cohort of dual diagnosis patients, the aim of this study was to quantify the patient-perceived problems and advantages of their substance use and relate the quantity of problems to the substance type and psychiatric diagnosis. MATERIAL: Data comes from a naturalistic cohort admitted to an in-patient facility in Denmark specialized in integrated dual diagnosis treatment. We included 1076 patients at their first admission to the facility from 2010 to 2017. Participants completed 607 DrugCheck and 130 DUDIT-E questionnaires. METHOD: we analyzed the questionnaires and included admission diagnosis by use of t-test and ANOVA to depict the patterns in substance use in relation to psychiatric diagnosis. RESULTS: The three most common substance related problems according to the DrugCheck questionnaire were: feeling depressed, financial problems, and losing interest in daily activities. From DUDIT-E, the highest-ranking negative substance related effects were financial ruin, deterioration of health, and problems at work. Effects on social life relationships were also evident with more than 40% of participants. The top three positive substance related effects reported were relaxation, improved sleep, and control over negative emotions. The number of problems listed varied significantly with the type of preferred substance. Patients using pain medication, sedatives, central stimulants, and alcohol reported most problems. Diagnosis did not differentiate the problems experienced. Results partially support the broad self-medication hypothesis for patients with severe mental illness, but also points out that patients are well aware of negative effects.

Polypharmacy in antipsychotic pharmacological treatment among patients with dual diagnosis in Denmark.

INTRODUCTION: Antipsychotic polypharmacy is prevalent, however literature on antipsychotic polypharmacy during treatment among patients with dual diagnosis is largely non-existent. This study aims to investigating the extent of antipsychotic polypharmacy dual diagnosis patients during hospitalisations. METHODS: Utilizing cohort data from an integrated dual diagnosis in-patient facility from patients hospitalized between 1 March 2012, to 31 December 2016, we compared the mean antipsychotic medication administered at admission and discharge and examined covariate associations with logistic regressions. RESULTS: The study identified 907 hospital admissions, of which 641 were the first for each patient during the period. At admission, 74.1% received antipsychotics; polypharmacy spanned psychiatric disorders. categories. Patients with affective or personality spectrum disorders were less likely to have antipsychotic polypharmacy upon admission compared to those with psychosis spectrum disorders. 2013-2016 admissions presented less polypharmacy than 2012. Mean antipsychotic numbers remained unchanged for >30-day hospitalizations. Patients admitted without antipsychotic polypharmacy with an affective spectrum disorder or aged 41-50 or over 51 years old were less likely to be discharged with antipsychotic polypharmacy when compared to patients with psychosis spectrum disorder or aged 18-30 years old. CONCLUSION: Approximately three-quarters of admitted patients were treated with antipsychotic medication. Antipsychotic polypharmacy was observed across all psychiatric disorder categories, indicating potential off-label use. Addressing antipsychotic polypharmacy during treatment is challenging, even for specialised facilities. Rational antipsychotic prescribing, deprescribing protocols, and further prescription pattern research are needed.

Virtual reality-assisted cognitive behavioural therapy for outpatients with alcohol use disorder (CRAVR): a protocol for a randomised controlled trial.

INTRODUCTION: Alcohol use disorder (AUD) is a brain disorder linked to over 200 health conditions. Cognitive behavioural therapy (CBT) is considered the best practice in the treatment of AUD, but more than 60% of patients relapse within the first year after treatment. Psychotherapy combined with virtual reality (VR) has received increasing interest in the treatment of AUD. However, existing studies have primarily investigated the use of VR for cue reactivity. We therefore aimed to investigate the effect of VR-assisted CBT (VR-CBT). METHODS AND ANALYSIS: This study is an assessor-blinded, randomised clinical trial being conducted at three outpatient clinics in Denmark. We will randomise 102 patients to 14 individual sessions of either manualised VR-CBT or CBT. The VR-CBT group will receive exposure to immersive high-risk VR situations from a pub, bar/party, restaurant, supermarket and at-home (30 videos) to activate high-risk-related beliefs and cravings for subsequent modification using CBT techniques. The treatment period is 6 months, and follow-up visits will be performed 3, 6, 9 and 12 months after inclusion. The primary outcome measure is the change in total alcohol consumption from baseline to 6 months after inclusion, measured with the Timeline Followback Method. Key secondary outcome measures include changes in the number of heavy drinking days, alcohol cravings, cognition, and symptoms of depression and anxiety. ETHICS AND DISSEMINATION: Approval has been obtained by the research ethics committee in the Capital Region of Denmark (H-20082136) and the Danish Data Protection Agency (P-2021-217). All patients will receive both oral and written information about the trial and written informed consent will be obtained from each patient before inclusion. The study results will be disseminated in peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov, NCT05042180.

Time trends in co-occurring substance use and psychiatric illness (dual diagnosis) from 2000 to 2017 - a nationwide study of Danish register data.

OBJECTIVE: This article aims to describe the time trend in number of dual diagnosis patients treated in the psychiatric system in Denmark from 2000 to 2017. METHOD: We calculated the share of patients with dual diagnosis, number of dual diagnosis contacts, number of unique individuals with dual diagnosis as well as number of new patients with dual diagnosis among patients in psychiatric treatment, i.e. among inpatients, outpatients and patients in emergency departments. In order to calculate this, we merged data from the National Patient Register (NPR), the National Registry of Alcohol Treatment, the National treatment registry for substance use, the National Prescription Registry and the Danish National Health Service register in the period from 2000 to 2017. RESULTS: We found an overall increase in patients with dual diagnosis in psychiatric treatment in Denmark from 2000 to 2017. We further detected an increase in the age and sex-standardized number of patients with dual diagnosis in treatment over time, however most markedly for outpatients. Further, inclusion of data from other sources of data than the NPR dramatically increased the number of patients that could be identified as dual diagnosis patients. Using these data, almost half of all male inpatients could be identified as dual diagnosis while the share was more than 40% for patients with schizophrenia, schizotypal and delusional disorders (F2) and patients with personality disorders (F6). CONCLUSIONS: The increase of individual diagnosis patients necessitates action at different levels. This includes improvement of preventive measures as well as improvement of treatment for this underserved group.

Patients' experiences with physical holding and mechanical restraint in the psychiatric care: an interview study.

BACKGROUND: In the continuous work to reduce the use of coercion in psychiatric care, attention in Denmark has especially been directed towards mechanical restraint. While the use of mechanical restraint is currently decreasing, an increase in other types of coercion is observed (e.g. medication and hour-long episodes of physical holding). Physical holding has, in this cultural context, been considered less intrusive to a patient's autonomy than the use of mechanical restraint. However, no study has yet compared the experiences of the patients on these two types of coercion in the same population. The objective of this study was to explore patients' perspectives on physical holding and mechanical restraint, respectively. METHODS: Audio-recorded, semi-structured interviews following an interview guide were conducted with patients sharing their experiences with both types of coercion. The interviews were transcribed verbatim. The analytical approach was based on the principles of thematic content analysis. RESULTS: Nine informants were interviewed between September 2020 and April 2021. Four main themes were identified: experiences with physical holding, experiences with mechanical restraint, the effects of coercion on patients and their relation to mental health care, and improved mental health care. CONCLUSION: It is inconclusive which type of restraint the patients preferred. This challenges the present hierarchy of coercive measures. To avoid coercion in the first place more communication and time with the patient are needed.

REDD-PAC Cohort Description: Researching Dual Diagnosis - Prognosis and Characteristics.

OBJECTIVE: Evidence from real-world integrated dual diagnosis treatment programs is limited. In 2017 we decided to establish the REDD-PAC cohort with the aim to provide more in-depth information regarding the effect of integrated treatment. METHODS: The REDD-PAC cohort includes more than 2,500 patients with dual diagnosis that have been treated at an in-patient department specializing in the integrated treatment of both psychiatric illness and substance use disorder in Denmark in the period from 2002 to 2017. The collected data included information on diagnosis as well as patient-completed questionnaires regarding anxiety, depression, self-worth, and use of substances. Data regarding medications prescribed and administered, weight, height, and blood pressure were also included. RESULTS: The primary diagnosis was psychosis spectrum disorder (37.0%), followed by affective disorders (18.8%). More than two-thirds of the patients were male, and most patients had a weak connection to the labor market and basic schooling. Patients were generally very motivated for treatment. CONCLUSIONS: Further linking the data to Danish national register data makes it possible to follow individual trajectories pre- and post-admission as well as to access complete follow-up data regarding long-term outcomes, e.g., use of health services, mortality, morbidity, crime, and social circumstances. This article describes both the overarching aims of the REDD-PAC cohort and the basic diagnostic and sociodemographic characteristics of the cohort.

Scalability of the Positive and Negative Syndrome Scale in first-episode schizophrenia assessed by Rasch models.

OBJECTIVE: Historically, assessment of the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) has had several foci: (1) calculation of reliability indexes, (2) extraction of subdimensions from the scale, and (3) assessment of the validity of the total score. In this study, we aimed to examine the scalability and to assess the clinical performance of the 30-item PANSS total score as well as the scalability of a shorter version (PANSS-6) of the scale. METHODS: A composite data set of 1073 patients with first-episode schizophrenia or schizophrenia spectrum disorder was subjected to Rasch analysis of PANSS data from baseline and 4-6 weeks follow-up. RESULTS: The central tests of fit of the Rasch model failed to satisfy the statistical requirements behind item homogeneity for the PANSS-30 as well as the PANSS-6 total score. For the PANSS-30, Differential Item Functioning was pronounced both for the 7-point Likert scale rating categories and when dichotomizing the rating categories. Subsequently, the Rasch structure analysis in the context of dichotomized items was used to isolate and estimate a systematic error because of item inhomogeneity, as well as a random error. The size of the combined sources of error for the PANSS-30 total score approximated 20% which is often regarded as clinical cut-off between response versus no-response. CONCLUSION: The results demonstrate the operational consequences of a lack of statistical fit of the Rasch model and suggest that the calculated measure of uncertainty needs to be considered when using the PANSS-30 total score.

[Virtual reality as therapy in psychiatry].

This review describes the growing research in virtual reality (VR) for healthcare purposes. In recent years, the technological improvements have expanded the possibility of investigating VR in diagnostics as well as treatment of mental and behavioural disorders. The existing literature regarding phobia, post-traumatic stress disorder, addiction, psychotic, eating and affective disorders is summarised and discussed in terms of clinical applicability.

Stability of admission diagnoses; data from a specialized in-patient treatment facility for dual diagnosis.

AIM: We investigated the stability of diagnoses during admission over an 11-year period in patients admitted to a highly specialized integrated dual diagnosis treatment facility in Denmark using diagnosis coded in patient charts. MATERIALS AND METHODS: Admission and discharge diagnoses from patient files were examined for stability of primary diagnosis and association with year of admission, age, sex, and duration of admission, in 1570 patients from 2007 to 2017. RESULTS: A vast proportion (69.6%) of the patients retained their diagnosis during a 3-month admission. Stability was highest for schizophrenia spectrum diagnoses and lowest for unspecified diagnosis. Type of primary diagnosis, age, and length of admission was associated with lower likelihood of a stable primary diagnosis. CONCLUSIONS: Long-term admission for psychiatric patients with substance use disorder (SUD) was significantly associated with stability of diagnosis. The finding calls for longer observation of dual diagnosis patients to ensure that relevant diagnosis is given, and consequently that the appropriate clinical treatment such as psychopharmacological as well as non-pharmacological intervention can be applied.

Rasch analysis of the PANSS negative subscale and exploration of negative symptom trajectories in first-episode schizophrenia - data from the OPTiMiSE trial.

The observed heterogeneity in negative symptom treatment response may be partly attributable to inadequate measurement tools or limitations in methods of analysis. Previous Item Response Theory models of the Positive and Negative Syndrome Scale (PANSS) have only examined samples of chronic patients and with mixed results. We examined the scalability of the negative subscale embedded in the PANSS and subsequently explored negative symptom trajectories across four weeks of amisulpride treatment. Data were derived from the OPTiMiSE trial comprising 446 patients with first-episode schizophrenia or schizophreniform disorder. Using the Rasch Model to examine psychometric properties of the PANSS negative subscale, we found that the composite score across items was not an adequate measure of negative symptom severity. Consequently, we chose an exploratory statistical approach involving Principal Component Analysis which yielded one significant component clustering into two significant symptom trajectories: 1) Subtle but constant decrease in negative symptom severity (N = 323; 72%), and 2) symptom instability across visits (N = 19; 4%). Explorative analytic methods as presented here may pave the way for more efficient and sensitive methods of analyzing negative symptom response in research and in clinical practice.

Sexual dysfunction and hyperprolactinemia in schizophrenia before and after six weeks of D2/3 receptor blockade - An exploratory study.

Sexual side-effects along with antipsychotic treatment may be linked to hyperprolactinemia and dopamine D2 receptor blockade. High prevalence of sexual dysfunction in un-medicated patients challenges the notion of sexual dysfunction as merely a side-effect of antipsychotic medication. Sexual dysfunction was assessed in fifty-six initially antipsychotic-naïve patients with schizophrenia using the UKU (Udvalget for Kliniske Undersøgelser) questionnaire. Serum-prolactin was obtained before and after six weeks of D2/3 receptor blockade with amisulpride. At baseline 68% of patients reported one or more items of sexual dysfunction (males > females,), but the cumulative load of sexual dysfunction was similar in males and females. After 6 weeks treatment with amisulpride (mean dose 279 mg/day), 65% of patients reported one or more items of sexual dysfunctions (females > males). There was a significant sex*time interaction on mean sexual dysfunction load. All patients developed hyperprolactinaemia, and a significant effect of time and sex was found on s-prolactin (females > males). The results support that patients with schizophrenia report high levels of sexual dysfunction before antipsychotic exposure. After treatment, sexual side-effects were more frequent in females, coinciding with pronounced serum-prolactin increases. These findings suggest sex differences in sexual dysfunction before and after antipsychotic treatment.

Associations between P3a and P3b amplitudes and cognition in antipsychotic-naïve first-episode schizophrenia patients.

BACKGROUND: Cognitive deficits are already present in early stages of schizophrenia. P3a and P3b event-related potentials (ERPs) are believed to underlie the processes of attention and working memory (WM), yet limited research has been performed on the associations between these parameters. Therefore, we explored possible associations between P3a/b amplitudes and cognition in a large cohort of antipsychotic-naïve, first-episode schizophrenia (AN-FES) patients and healthy controls (HC). METHODS: Seventy-three AN-FES patients and 93 age- and gender-matched HC were assessed for their P3a/b amplitude with an auditory oddball paradigm. In addition, subjects performed several subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: AN-FES patients had significantly reduced P3a/b amplitudes, as well as significantly lower scores on all cognitive tests compared with HC. Total group correlations revealed positive associations between P3b amplitude and WM and sustained attention and negative associations with all reaction time measures. These associations appeared mainly driven by AN-FES patients, where we found a similar pattern. No significant associations were found between P3b amplitude and cognitive measures in our HC. P3a amplitude did not correlate significantly with any cognitive measures in either group, nor when combined. CONCLUSIONS: Our results provide further evidence for P3a/b amplitude deficits and cognitive deficits in AN-FES patients, which are neither due to antipsychotics nor to disease progress. Furthermore, our data showed significant, yet weak associations between P3b and cognition. Therefore, our data do not supply evidence for deficient P3a/b amplitudes as direct underlying factors for cognitive deficits in schizophrenia.

Male circumcision does not result in inferior perceived male sexual function - a systematic review.

INTRODUCTION: The debate on non-medical male circumcision has gaining momentum during the past few years. The objective of this systematic review was to determine if circumcision, medical indication or age at circumcision had an impact on perceived sexual function in males. METHODS: Systematic searches were performed in MEDLINE and Embase. The included studies compared long-term sexual function in circumcised and non-circumcised males, before and after circumcision, or compared different ages at circumcision. The quality of the studies was assessed according to the level of evidence (Grade A-D). RESULTS: Database and hand searches yielded 3,677 records. Inclusion criteria were fulfilled in 38 studies including two randomised trials. Overall, the only identified differences in sexual function in circumcised males were decreased premature ejaculation and increased penile sensitivity (Grade A-B). Following non-medical circumcision, no inferior sexual function was reported (A-B). Following medical circumcision, most outcomes were comparable (B); however, problems in obtaining an orgasm were increased (C) and erectile dysfunction was reported with inconsistency (D). A younger age at circumcision seemed to cause less sexual dysfunction than circumcision later in life. CONCLUSIONS: The hypothesis of inferior male sexual function following circumcision could not be supported by the findings of this systematic review. However, further studies on medical circumcision and age at circumcision are required.

Effects of Blocking D2/D3 Receptors on Mismatch Negativity and P3a Amplitude of Initially Antipsychotic Naïve, First Episode Schizophrenia Patients.

BACKGROUND: Reduced mismatch negativity and P3a amplitude have been suggested to be among the core deficits in schizophrenia since the late 1970s. Blockade of dopamine D2 receptors play an important role in the treatment of schizophrenia. In addition, there is some evidence indicating that deficits in mismatch negativity and P3a amplitude are related to increased dopaminergic activity. This is the first study investigating the effect of amisulpride, a potent D2-antagonist, on mismatch negativity and P3a amplitude in a large group of antipsychotic-naïve, first-episode schizophrenia patients. METHODS: Fifty-one antipsychotic-naïve, first-episode schizophrenia patients were tested in a mismatch negativity paradigm at baseline and after 6 weeks of treatment with amisulpride. We further examined 48 age- and gender-matched controls in this paradigm. RESULTS: At baseline, the patients showed significantly reduced P3a amplitude compared with healthy controls, but no differences in mismatch negativity. Although the treatment with amisulpride significantly improved the patients' psychopathological (PANSS) and functional (GAF) scores, it did not influence their mismatch negativity amplitude, while also their reduced P3a amplitude persisted. CONCLUSION: Our findings show that antipsychotic naïve, first-episode patients with schizophrenia have normal mismatch negativity yet reduced P3a amplitude compared with healthy controls. In spite of the fact that the 6-week amisulpride treatment improved the patients both clinically and functionally, it had no effect on either mismatch negativity or P3a amplitude. This suggests that even though there is a dopaminergic involvement in global functioning and symptomatology in schizophrenia, there is no such involvement in these particular measures of early information processing.

Effects of dopamine D2/D3 blockade on human sensory and sensorimotor gating in initially antipsychotic-naive, first-episode schizophrenia patients.

It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating deficits in a longitudinal study of a large group of initially antipsychotic-naive, first-episode patients with schizophrenia. Our finding that amisulpride effectively reduced symptom severity in our patients without reducing their PPI deficits indicates that increased activity of dopamine D2 receptors may be involved in symptomatology of patients with schizophrenia, but not in their sensorimotor gating deficits.