The effectiveness of blended versus regular Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: a study protocol of a randomized controlled trial

Background: Antisocial behavior during adolescence can have long-lasting negative effects and leads to high societal costs. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles aged 12–21 showing severe antisocial behavior. The intensity, content and duration of FAST can be adjusted to the needs of the juvenile and their caregiver(s), which is considered crucial for effective treatment. Next to the regular version of FAST (FASTr), a blended version (FASTb) in which face-to-face contacts are replaced by minimally 50% online contacts over the duration of intervention was developed during the Covid-19 pandemic. The current study will investigate whether FASTb is equally effective as FASTr, and through which mechanisms of change, for whom, and under which conditions FASTr and FASTb work. Methods: A randomized controlled trial (RCT) will be carried out. Participants (N = 200) will be randomly assigned to FASTb (n = 100) or FASTr (n = 100). Data collection will consist of self-report questionnaires and case file analysis, and include a pre-test at the start of the intervention, a post-test immediately after the intervention, and a six month follow-up. Mechanisms of change will be investigated using monthly questionnaires of key variables during treatment. Official recidivism data will be collected at two-year follow-up. Discussion: This study aims to improve the effectiveness and quality of forensic mental health care for juveniles with antisocial behavior by studying the effectiveness of blended care, which has not been studied before in treatment of externalizing behavior. If found to be at least as effective as face-to-face treatment, blended treatment can help meet the urgent need for more flexible and efficient interventions in this field. In addition, the proposed study aims to unravel what works for whom, knowledge urgently needed in mental health care for juveniles with severe antisocial behavior. Trial registration: This trial was registered at ClinicalTrials.gov on 07/11/2022, registration number NCT05606978

Strategies for Treating Latent Multiple-Drug Resistant Tuberculosis: A Decision Analysis

BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers

The Role of Control in Intimate Partner Violence: A study in Dutch Forensic outpatients

Johnson (1995) argued that coercive control is crucial in explaining heterogeneity in intimate partner violence, with such violence being more frequent, less reciprocal, and more often male-to-female aggression when it serves to exercise control over the partner. We assessed 280 Dutch forensic outpatients who had recently engaged in intimate partner violence on non-aggressive coercive control. Control showed significant, small to moderate, associations with more frequent past year acts of psychological aggression, physical assault, sexual coercion and more frequently resulted in partner injury. Control was unrelated to reciprocity of partner violence. High controlling violence was enacted mostly, but not exclusively by men. Overall, while perhaps not having a uniquely strong association, our findings provide partial support for the role of coercive control in intimate partner violence, and suggest it may benefit intimate partner violence risk assessment

Risicotaxatie in de Nederlandse ambulante forensische geestelijke gezondheidszorg

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Kernset K-Factoren voor het ambulante forensische veld: Een Multi-method onderzoek naar risico- en beschermende factoren in relatie tot algemene recidive, geweldsrecidive en seksuele recidive

In opdracht van KFZ werd onderzoek gedaan naar de statische en dynamische risico- en beschermende factoren die het sterkst met recidive samenhangen. Het uitgangspunt was om, vertrekkend vanuit het RNR-model, een kernset van factoren te identificeren die voor het grootste deel van de ambulante forensische populatie zou gelden. De projectgroep heeft gekozen voor een multi-method design (meta-analyses, secundaire data-analyse op prospectieve data, veldonderzoek) waarbij de focus lag op de empirische onderbouwing van de kernset. In dit hoofdstuk worden kort de bevindingen weergegeven van de deelstudies die ten behoeve van de opdracht werden uitgevoerd

The effectiveness of blended versus regular Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: a study protocol of a randomized controlled trial

Abstract Background Antisocial behavior during adolescence can have long-lasting negative effects and leads to high societal costs. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles aged 12–21 showing severe antisocial behavior. The intensity, content and duration of FAST can be adjusted to the needs of the juvenile and their caregiver(s), which is considered crucial for effective treatment. Next to the regular version of FAST (FASTr), a blended version (FASTb) in which face-to-face contacts are replaced by minimally 50% online contacts over the duration of intervention was developed during the Covid-19 pandemic. The current study will investigate whether FASTb is equally effective as FASTr, and through which mechanisms of change, for whom, and under which conditions FASTr and FASTb work. Methods A randomized controlled trial (RCT) will be carried out. Participants (N = 200) will be randomly assigned to FASTb (n = 100) or FASTr (n = 100). Data collection will consist of self-report questionnaires and case file analysis, and include a pre-test at the start of the intervention, a post-test immediately after the intervention, and a six month follow-up. Mechanisms of change will be investigated using monthly questionnaires of key variables during treatment. Official recidivism data will be collected at two-year follow-up. Discussion This study aims to improve the effectiveness and quality of forensic mental health care for juveniles with antisocial behavior by studying the effectiveness of blended care, which has not been studied before in treatment of externalizing behavior. If found to be at least as effective as face-to-face treatment, blended treatment can help meet the urgent need for more flexible and efficient interventions in this field. In addition, the proposed study aims to unravel what works for whom, knowledge urgently needed in mental health care for juveniles with severe antisocial behavior. Trial registration This trial was registered at ClinicalTrials.gov on 07/11/2022, registration number NCT05606978