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A. Džubur Kulenović

Društvene mreže:

S. Bajraktarov, Biljana Blazhevska Stoilkovska, Manuela Russo, S. Repišti, Nadja P. Maric, A. Džubur Kulenović, A. Arënliu, L. Stevović, L. Novotni et al.

The Brief Psychiatric Rating Scale (BPRS) is a useful tool for measuring the severity of psychopathological symptoms among patients with psychosis. Many studies, predominantly in Western countries, have investigated its factor structure. This study has the following aims: (a) to further explore the factor structure of the BPRS-Expanded version (BPRS-E, 24 items) among outpatients with psychotic disorders in Southeast European countries; (b) to confirm the identified model; and (c) to investigate the goodness-of-fit of the three competing BPRS-E factor models derived from previous studies. The exploratory factor analysis (EFA) produced a solution with 21 items grouped into five factors, thus supporting the existence of a fifth factor, i.e., Disorganization. A follow-up confirmatory factor analysis (CFA) revealed a 19-item model (with two items removed) that fit the data well. In addition, the stability of two out of three competing factor models was confirmed. Finally, the BPRS-E model with 5 factors developed in this cross-national study was found to include a greater number of items compared to competing models.

M. Russo, D. Ignjatović-Ristić, D. Cohen, Aliriza Arenliu, S. Bajraktarov, A. Džubur Kulenović, L. Injac Stevović, N. Maric, A. Novotni et al.

Introduction International reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia. Methods Descriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime. Results It was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol). Discussion Our findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.

Y. Feng, C. Roukas, M. Russo, S. Repišti, A. Džubur Kulenović, L. Injac Stevović, J. Konjufca, S. Markovska-Simoska, L. Novotni et al.

Abstract Background DIALOG+ is a digital psychosocial intervention aimed at making routine meetings between patients and clinicians therapeutically effective. This study aimed to evaluate the cost-effectiveness of implementing DIALOG+ treatment for patients with psychotic disorders in five low- and middle-income countries in Southeast Europe alongside a cluster randomised trial. Methods Resource use and quality of life data were collected alongside the multi-country cluster randomised trial of 468 participants with psychotic disorders. Due to COVID-19 interruptions of the trial’s original 12-month intervention period, adjusted costs and quality-adjusted life years (QALYs) were estimated at the participant level using a mixed-effects model over the first 6 months only. We estimated the incremental cost-effectiveness ratio (ICER) with uncertainty presented using a cost-effectiveness plane and a cost-effectiveness acceptability curve. Seven sensitivity analyses were conducted to check the robustness of the findings. Results The average cost of delivering DIALOG+ was €91.11 per participant. DIALOG+ was associated with an incremental health gain of 0.0032 QALYs (95% CI –0.0015, 0.0079), incremental costs of €84.17 (95% CI –8.18, 176.52), and an estimated ICER of €26,347.61. The probability of DIALOG+ being cost-effective against three times the weighted gross domestic product (GDP) per capita for the five participating countries was 18.9%. Conclusion Evidence from the cost-effectiveness analyses in this study suggested that DIALOG+ involved relatively low costs. However, it is not likely to be cost-effective in the five participating countries compared with standard care against a willingness-to-pay threshold of three times the weighted GDP per capita per QALY gained.

E. Ribic, H. Sikira, A. Džubur Kulenović, T. Pemovska, M. Russo, N. Jovanović, T. Radojičić, S. Repišti, Milos Milutinovic et al.

Background DIALOG+ is an evidence-based, generic, cost-saving and easily deliverable psychosocial intervention, adaptable to clinicians’ personal manner of interaction with patients. It was implemented in mental health services in five low- and middle-income countries in South-Eastern Europe during a 12-month randomised-controlled trial (IMPULSE) to improve the effectiveness of out-patient treatment for people with psychotic disorders. Aims To investigate barriers and facilitators to the perceived sustainability of DIALOG+ that has been successfully implemented as a part of the IMPULSE project. Method Three months after the IMPULSE trial's end, perceived sustainability of the DIALOG+ intervention was assessed via a short survey of clinicians and patients who took part in the trial. Quantitative data collected from the survey were analysed using descriptive statistics; content analysis assessed qualitative survey data. The views and experiences of key informants (patients, clinicians and healthcare policy influencers) regarding the sustainability and scale-up of DIALOG+ were further explored through semi-structured interviews. These data were explored using framework analysis. Results Clinicians mostly appreciated the comprehensiveness of DIALOG+, and patients described DIALOG+ meetings as empowering and motivating. The barrier most commonly identified by key informants was availability of financial resources; the most important facilitators were the clinically relevant structure and comprehensiveness of the DIALOG+ intervention. Conclusions Participants showed a willingness to sustain the implementation of DIALOG+. It is important to maintain collaboration with healthcare policy influencers to improve implementation of DIALOG+ across different levels of healthcare systems and ensure availability of resources for implementing psychosocial interventions such as DIALOG+.

N. Jovanovic, M. Russo, T. Pemovska, J. Francis, Aliriza Arenliu, S. Bajraktarov, A. Džubur Kulenović, L. Injac Stevović, A. Novotni et al.

Abstract Background In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2). Methods A hybrid type II effectiveness–implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression. Results A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable. Conclusions DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.

N. Maric, S. Andric Petrovic, M. Russo, S. Jerotić, I. Ristić, Bojana Savić, T. Pemovska, Milos Milutinovic, E. Ribic et al.

Background Maintenance therapy of patients with primary psychosis spectrum disorders (PSD) in the Western Balkans has received limited interest so far. The present study aimed to investigate long-term prescription patterns among outpatients with PSD. Methods Information about prescription of antipsychotics (AP), benzodiazepines (BZD) and other psychotropic medication over a 6-month period was collected from outpatients (n = 134; ICD-10 diagnosis F20-29) recruited by a larger multi-site study, to find mean daily number of psychotropic drugs, AP prescription patterns (including AP daily dose, route of administration, monotherapy vs. polypharmacy) and BZD utilization (long-term add-on BZD therapy). Additionally, sex-differences in the variables were explored. Results Clinically stable outpatients (age 41.7 ± 11.0; male 62.7%; duration of untreated illness 12.7 ± 8.7 years; mean number of lifetime hospitalizations 2.6 ± 0.7) were prescribed 2.8 ± 1.1 psychotropic medications daily. The mean 6-month AP dose was 14.2 ± 7.8 mg olanzapine equivalents. Long-acting injectable AP was prescribed to 25.2% of the patients. Long-term AP monotherapy was found in 52.7% patients and most of them were prescribed second generation AP (65.2%). Long-term AP polypharmacy (42.7%) was more common in males (p = 0.015). The most frequent co-prescription patterns were first generation AP plus clozapine. The highest rate of long-term AP co-prescription was found for BZD (in 42.7% cases, average 6-months daily dose of 2.8 ± 2.7 mg lorazepam equivalents) and anticholinergics (33.6%). Conclusion Existing appropriately designed interventions aiming to safely switch the inappropriate therapeutic regimens, i.e. very high prevalence of long-term AP polypharmacy and non-rational BZD co-prescription, should be implemented in the region of Western Balkans.

M. Russo, S. Repišti, Biljana Blazhevska Stoilkovska, S. Jerotić, I. Ristić, Eldina Mesevic Smajic, F. Uka, Aliriza Arenliu, S. Bajraktarov et al.

[This corrects the article DOI: 10.3389/fpsyt.2021.785144.].

M. Russo, S. Repišti, Biljana Blazhevska Stoilkovska, S. Jerotić, I. Ristić, Eldina Mesevic Smajic, F. Uka, Aliriza Arenliu, S. Bajraktarov et al.

Background: Negative symptoms are core features of schizophrenia and very challenging to be treated. Identification of their structure is crucial to provide a better treatment. Increasing evidence supports the superiority of a five-factor model (alogia, blunted affect, anhedonia, avolition, and asociality as defined by the NMIH-MATRICS Consensus); however, previous data primarily used the Brief Negative Symptoms Scale (BNSS). This study, including a calibration and a cross-validation sample (n = 268 and 257, respectively) of participants with schizophrenia, used the Clinical Assessment Interview for Negative Symptoms (CAINS) to explore the latent structure of negative symptoms and to test theoretical and data-driven (from this study) models of negative symptoms. Methods: Exploratory factor analysis (EFA) was carried out to investigate the structure of negative symptoms based on the CAINS. Confirmatory factor analysis (CFA) tested in a cross-validation sample four competing theoretical (one-factor, two-factor, five-factor, and hierarchical factor) models and two EFA-derived models. Result: None of the theoretical models was confirmed with the CFA. A CAINS-rated model from EFA consisting of five factors (expression, motivation for recreational activities, social activities, vocational, and close/intimate relationships) was an excellent fit to the data (comparative fix index = 0.97, Tucker–Lewis index = 0.96, and root mean square error of approximation = 0.07). Conclusions: This study cannot support recent data on the superiority of the five-factor model defined by the NMIH-MATRICS consensus and suggests that an alternative model might be a better fit. More research to confirm the structure of negative symptoms in schizophrenia, and careful methodological consideration, should be warranted before a definitive model can put forward and shape diagnosis and treatment of schizophrenia.

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