Search

Esther Pars,1– 4 Fadi Hirzalla,5 Joanne EL VanDerNagel,2,3,6,7 Boukje AG Dijkstra,2,8,9 Arnt FA Schellekens1,2 1Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands; 2Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), Nijmegen, the Netherlands; 3Department of Human Media Interaction, University of Twente, Enschede, the Netherlands; 4Salvation Army, Ugchelen, The Netherlands; 5Department of Public Administration and Sociology, Erasmus University, Rotterdam, the Netherlands; 6Tactus Addiction Care, Deventer, the Netherlands; 7Aveleijn, Borne, the Netherlands; 8Novadic-Kentron, Vught, the Netherlands; 9Behavioral Science Institute, Radboud University, Nijmegen, the NetherlandsCorrespondence: Esther Pars, Department of Psychiatry, Radboud University Medical Center, PO Box 9101, Nijmegen, 6500 HB, the Netherlands, Tel +31 24 361 35 13, Email Esther.Pars-vanWeeterloo@radboudumc.nlPurpose: Substance use disorder (SUD) can be a chronic relapsing condition with poor treatment outcomes. Studies exploring factors associated with abstinence or relapse after treatment are often quantitative in nature, applying linear statistical approaches, while abstinence and relapse result from non-linear, complex, dynamic and synergistic processes. This study aims to explore these underlying dynamics using qualitative comparative analysis (QCA) as a mixed methods approach to further our understanding of factors contributing to post-treatment abstinence and relapse.Patients and Methods: In a prospective study, we gathered both qualitative and quantitative data pertaining to post-treatment substance use and the factors linked to substance use outcomes. These factors encompassed psychiatric comorbidity, intellectual disability, social disintegration, post-treatment support, and engagement in activities among patients who had undergone inpatient treatment for severe SUD (n = 58). QCA, a set-theoretic approach that considers the complex interplay of multiple conditions, was applied to discern which factors were necessary or sufficient for the occurrence of either abstinence or relapse.Results: We found two solutions predicting abstinence, and five for relapse. Post-treatment conditions (support and engagement in activities) were important for retaining abstinence. For relapse, individual baseline characteristics (intellectual disability, social disintegration, psychiatric comorbidity) combined with (post-)treatment factors (post-treatment support, activities) were important.Conclusion: Although abstinence and relapse represent opposing outcomes, they each exhibit distinct dynamics. To gain a comprehensive understanding of these dynamics, it is advisable to examine them as separate outcomes. For clinical practice, it can be worthwhile to recognize that fostering the conditions conducive to abstinence may differ from preventing the factors that trigger relapse.Plain Language Summary: This study explores why some people who struggle with addiction stay clean after treatment, while others relapse. Previous studies often used traditional statistical methods, with inconclusive results due to their inability to capture the complexity of this process. To address this, we used a different approach called qualitative comparative analysis (QCA).We collected information from 58 individuals who received inpatient treatment for their addiction. We looked at different factors like mental health problems, intellectual disability, the support they got from professionals and their social network, and whether they kept themselves busy with activities. We investigated how these factors are related to staying clean or relapse. With the help of QCA, we analyzed how these factors work together to cause either drug-free living or relapse.We found that staying clean was strongly linked to getting support after treatment and being involved in activities like hobbies or work. On the other hand, relapse was more likely in people with personal problems, like intellectual disabilities and mental health problems, when support and activities were lacking after treatment.In summary, our study indicates that staying clean and relapse are different processes with different factors at play. Helping someone stay clean may therefore require different strategies than preventing relapse. This insight can guide development of more personalized healthcare for individuals dealing with addiction.Keywords: addiction, substance use outcomes, qualitative comparative analysis

Objectives: The COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known. Given the ongoing increase in opioid-related harm and mortality, it is crucial to analyse the impact of the COVID-19 crisis and lockdown measures on opioid prescribing. Therefore, the objective of this study was to characterise opioid prescribing in the Netherlands during the COVID-19 pandemic., Design: A nationwide register-based study characterising opioid prescribing using aggregated insurance reimbursement data., Setting: Dutch healthcare during the first 2 years of the COVID lockdown., Participants: The whole Dutch population., Primary and Secondary Outcome Measures: Comparing the number of opioid prescriptions during the pandemic with a prepandemic period using a risk ratio (RR), with separate analysis on the prescription type (first-time or repeat prescription), patients' sex, age and socioeconomic status. We also explored lockdown effects., Results: During the first lockdown, the total number of new opioid prescriptions and prescriptions to young patients (briefly) decreased (RR 0.88, 95% CI 0.88 to 0.89 and RR 0.73, 95% CI 0.70 to 0.75, respectively), but the overall number of opioid prescriptions remained stable throughout the pandemic compared with prepandemic. Women, older patients and patients living in lower socioeconomic areas received more opioids per capita, but the pandemic did not amplify these differences., Conclusions: The pandemic appears to have had a limited impact on opioid prescribing in the Netherlands. Yet, chronic use of opioids remains an important public health issue., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression., (© 2024. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic and related restrictions globally impacted mental health, particularly for those with pre-existing severe mental illness (SMI). This qualitative study examined how adults with SMI perceived the effects of the COVID-19 pandemic and related restrictions in the Netherlands, focusing on their personal recovery, well-being and daily life, including an exploration of factors influencing these effects., Methods: Semi-structured interviews were conducted, audio-recorded and transcribed verbatim. Reflexive thematic analysis was applied. Purposive sampling was used to ensure diversity of individuals with SMI (i.e., age, gender, diagnosis, cultural background and mental healthcare institution)., Results: Twenty participants (median age: 45 years [SD: 12, 8]; 11 females) were interviewed between May and July 2023. Findings revealed a wide range of experiences: while some individuals reported a negative impact on their existing psychiatric symptoms, others described adaptability, resilience and even positive effects of COVID-19 restrictions on their mental health and well-being. Factors influencing the heterogeneic perceptions of the COVID-19 pandemic and related restrictions include the availability of trusted social relationships and enduring interactions with health professionals., Conclusion: Personalised support, both socially and professionally, is crucial for addressing fears, building resilience, reducing isolation and encouraging positive coping strategies for individuals with SMI during external crises. In this project, a participatory research approach that integrated the lived experience perspective helped uncover the unique perceptions of people with SMI with regard to the pandemic and related restrictions., Patient or Public Contribution: The study used a participatory action research approach, with experts-by-experience involved in every stage of the project as part of the research team. This included engagement with the funding application process, recruitment strategies for interviews, developing the interview guide, piloting the interview, interpreting findings, and knowledge dissemination activities., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Recovery capital (RC) encompasses the wide range of resources individuals can employ to recover from Substance Use Disorder (SUD). It consists of five subdomains: human, social, cultural, financial, and community RC. Negative recovery capital (NRC) represents the obstacles to recovery. Research on (N)RC in complex multimorbid populations is scarce. This study offers an initial exploration of the viability of (N)RC in three individuals with SUD, psychiatric comorbidities, and an intellectual disability (a triple diagnosis) in inpatient addiction treatment. We collected case file data, ranked recovery goals, and conducted follow-up interviews. The data were subjected to template analysis, using (N)RC domains as codes. All domains were prevalent and relevant, showing dynamic and reciprocal effects, influenced by critical life events acting as catalysts. Notably, during treatment, patients prioritized individual skill development despite challenges in other domains. RC emerges as a valuable concept for mapping recovery barriers and facilitators in individuals with a triple diagnosis, serving as an alternative to the medical model and complementing the biopsychosocial model. It provides a systematic framework to assess critical factors for recovery in complex cases and accordingly align interventions. Future studies should explore the intersections of NRC domains and the dynamic nature of (N)RC to enhance the understanding of the challenges faced by individuals with a triple diagnosis.

Background: Mindfulness-based interventions have a positive impact on pain, craving, and well-being in both patients with chronic pain and those with opioid use disorder (OUD). Although data are limited, mindfulness-based cognitive therapy (MBCT) might be a promising treatment for patients with chronic noncancer pain combined with OUD. The aim of this qualitative study was to explore the feasibility and process of change during MBCT in this particular population., Methods: In this qualitative pilot study, 21 patients who were hospitalized for rotation to buprenorphine/naloxone as agonist treatment for chronic pain and OUD were offered MBCT. Semistructured interviews were conducted to explore experienced barriers and facilitators to MBCT. Patients who participated in MBCT were also interviewed on their perceived process of change., Results: Of 21 patients invited to participate in MBCT, 12 initially expressed interest but only four eventually participated in MBCT. The timing of the intervention, group format, somatic complaints, and practical difficulties were identified as the main barriers to participation. Facilitating factors included having a positive attribution toward MBCT, an intrinsic motivation to change, and practical support. The four MBCT participants mentioned several important mechanisms of change, including reduction of opioid craving and improved coping with pain., Conclusions: MBCT offered in the current study was not feasible for the majority of patients with pain and OUD. Changing the timing of MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.

Importance: Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects., Objective: To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD)., Design, Setting, and Participants: This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications., Intervention: In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage., Main Outcomes and Measures: The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores)., Results: Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT., Conclusions and Relevance: In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD., Trial Registration: ClinicalTrials.gov Identifier: NCT03548675.

The neurotransmitter γ-hydroxybutyric acid (GHB) is suggested to be involved in neuronal energy homeostasis processes, but the substance is also used as a recreational drug and as a prescription medication for narcolepsy. GHB has several high-affinity targets in the brain, commonly generalized as the GHB receptor. However, little is known about the structural and functional properties of GHB receptor subtypes. This opinion article discusses the literature on the putative structural and functional properties of the GHBh1 receptor subtype. GHBh1 contains 11 transmembrane helices and at least one intracellular intrinsically disordered region (IDR). Additionally, GHBh1 shows a 100% overlap in amino acid sequence with the Riboflavin (vitamin B2) transporter, which opens the possibility of a possible dual-function (transceptor) structure. Riboflavin and GHB also share specific neuroprotective properties. Further research into the GHBh1 receptor subtype may pave the way for future therapeutic possibilities for GHB.

Background: Prescription opioid use has increased steadily in many Western countries over the past two decades, most notably in the US, Canada, and most European countries, including the Netherlands. Especially the increasing use of prescription opioids for chronic non-cancer pain has raised concerns. Most opioids in the Netherlands are prescribed in general practices. However, little is known about variation in opioid prescribing between general practices. To better understand this, we investigated practice variation in opioid prescribing for non-cancer pain between Dutch general practices., Methods: Data from 2017-2019 of approximately 10% of all Dutch general practices was used. Each year included approximately 1000000 patients distributed over approximately 380 practices. The primary outcome was the proportion of patients with chronic (>90 days) high-dose (≥90 oral morphine equivalents) opioid prescriptions. The secondary outcome was the proportion of patients with chronic (<90 oral morphine equivalents) opioid prescriptions. Practice variation was expressed as the ratio of the 95th/5th percentiles and the ratio of mean top 10/bottom 10. Funnel plots were used to identify outliers. Potential factors associated with unwarranted variation were investigated by comparing outliers on practice size, patient neighbourhood socioeconomic status, and urbanicity., Results: Results were similar across all years. The magnitude of variation for chronic high-dose opioid prescriptions in 2019 was 7.51-fold (95%/5% ratio), and 15.1-fold (top 10/bottom 10 ratio). The percentage of outliers in the funnel plots varied between 13.8% and 21.7%. Practices with high chronic high-dose opioid prescription proportions were larger, and had more patients from lower income and densely populated areas., Conclusions: There might be unwarranted practice variation in chronic high-dose opioid prescriptions in primary care, pointing at possible inappropriate use of opioids. This appears to be related to socioeconomic status, urbanicity, and practice size. Further investigation of the factors driving practice variation can provide target points for quality improvement and reduce inappropriate care and unwarranted variation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kalkman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets., Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort., Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis -women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine., Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV., Competing Interests: All authors are part of the 2000HIV collaboration, which is supported by ViiV Healthcare. ViiV Healthcare funded this research and the included authors employed by the company contributed in the writing of the final manuscript. Although there is close collaboration, ViiV Healthcare did not have any role in data quality control, statistical analyses and final interpretation of the data.Author CR received grants from Gilead sciences, ViiV Healthcare, Janssen-Cilag, Health Holland, AIDSfonds, ErasmusMC, outside the submitted work. Authors EW, SVV, MK and JL are employed by ViiV healthcare. Authors QM and AJV received grants from Sysmex Corporation. Author TH is employed by Sysmex Corporation., (Copyright © 2022 Vos, Groenendijk, Blaauw, van Eekeren, Navas, Cleophas, Vadaq, Matzaraki, dos Santos, Meeder, Fröberg, Weijers, Zhang, Fu, ter Horst, Bock, Knoll, Aschenbrenner, Schultze, Vanderkerckhove, Hwandih, Wonderlich, Vemula, van der Kolk, de Vet, Blok, Brinkman, Rokx, Schellekens, de Mast, Joosten, Berrevoets, Stalenhoef, Verbon, van Lunzen, Netea and van der Ven.)

Background: People who use drugs (PWUD) are at high risk for hepatitis C virus (HCV) infection and its complications. Given the high prevalence rate of HCV in PWUD, the World Health Organization (WHO) emphasizes PWUD as a target population for HCV elimination. The introduction of pangenotypic direct acting antivirals (DAAs) greatly simplifies HCV treatment, which encourages integration of HCV treatment in primary care. Facilitating low threshold HCV care for PWUD by implementing decentralized models is crucial for HCV elimination., Aims: With this study we aim to (1) eliminate 90% of identified HCV infections in Dutch addiction care, using a decentralized PWUD-HCV care model, and (2) identify facilitators and barriers for successful implementation of the model using interviews., Methods: We will perform a multicenter mixed-method study on HCV treatment in addiction care. In a prospective observational study we will examine HCV-related outcomes in PWUD receiving HCV treatment as part of addiction care. The primary outcome is viral elimination, defined as percentage of identified HCV positive patients cured with DAAs. In parallel, we will perform a qualitative study to explore facilitators and barriers for implementation of fully decentralized HCV-PWUD care. We will interview addiction care professionals and board members about their experience with HCV-care as part of addiction care., Discussion: This study will show effectiveness of integration of HCV care within addiction care, and provide insight in facilitators and barriers to implement integrated HCV-addiction care. The results will provide recommendations for implementation and maintenance of the decentralized HCV pathway, which can facilitate scaling-up to contribute to reaching WHO HCV elimination goals. Trial registration NCT05401136., (© 2022. The Author(s).)

Background: Opioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited., Methods: This two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms., Discussion: This is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD. Trial registration https://www.trialregister.nl/ , NL9781., (© 2022. The Author(s).)

The elimination of viral hepatitis in target populations is crucial in reaching WHO viral hepatitis elimination goals. Several barriers for the treatment of viral hepatitis in people with addictive disorders have been identified, yet nationwide data on hepatitis healthcare utilization (HCU) in these patients are limited. We investigated whether a history of addictive disorder is associated with suboptimal hepatitis HCU, indicating failure to receive diagnostic care or treatment. We identified all newly referred viral hepatitis patients in the Netherlands between 2014 and 2019 by query of the Dutch national hospital claims database. Each patient's first year of HBV or HCV care activities was collected and clustered in two categories, 'optimal' or 'suboptimal' hepatitis HCU. Optimal HCU includes antiviral therapy. We tested the association between addiction history and HCU, adjusted for sex, age, migrant status, and comorbidity. In secondary analyses, we explored additional factors affecting hepatitis HCU. We included 10,513 incident HBV and HCV patients, with 13% having an addiction history. Only 47% of all patients achieved optimal hepatitis HCU. Addiction history was associated with less suboptimal HCU (adjusted OR = 0.73, 95% CI = 0.64-0.82). Migration background was associated with suboptimal HCU (OR = 1.62, 95% CI = 1.50-1.76). This study shows that addiction history is associated with higher viral hepatitis HCU; thus, this population performs better compared to non-addicted patients. However, less than 50% of all patients received optimal hepatitis care. This study highlights the need to improve hepatitis HCU in all patients, with a focus on migrant populations. Linkage to care in the addicted patients is not studied here and may be a remaining obstacle to be studied and improved to reach WHO viral hepatitis elimination goals.

Patients with chronic non-cancer pain (CNCP) often use opioids for long periods of time. This may lead to opioid use disorder (OUD) and psychiatric symptoms: mainly depression and anxiety. The current study investigated the effect of buprenorphine/naloxone (BuNa) rotation on opioid misuse, craving, psychiatric symptoms and pain in patients with CNCP and OUD. Forty-three participants with CNCP and OUD were converted from a full mu-receptor agonist opioid (mean morphine equivalent dose: 328.3 mg) to BuNa, in an inpatient setting. Opioid misuse, craving, co-occurring psychiatric symptoms, and pain perception were determined at baseline and after a two-month follow-up, using the following self-report questionnaires: Current Opioid Misuse Measurement (COMM), Visual Analog Scale (VAS-craving and VAS-pain) and Depression, Anxiety and Stress Scale (DASS), respectively. VAS-craving and VAS-pain were also determined immediately after conversion. A total of 37 participants completed the protocol. The mean COMM decreased from 17.1 to 6.7 (F = 36.5; p < 0.000), the mean VAS-craving decreased from 39.3 to 5.3 (-86.6%; F = 26.5, p < 0.000), the mean DASS decreased from 12.1 to 6.6 (F = 56.3, p < 0.000), and the mean VAS-pain decreased from 51.3 to 37.2 (-27.4%, F = 3.3; p = 0.043). Rotation to BuNa in patients with CNCP and OUD was accompanied by reductions in (i) opioid misuse, (ii) opioid craving, (iii) the severity of co-occurring psychiatric symptoms, and (iv) self-reported pain. BuNa as opioid agonist treatment may therefore be a beneficial strategy in CNCP patients with OUD. The limited sample size and the observational nature of this study underline the need for the replication of the current findings in large-scale, controlled studies.

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking. This study aimed to (1) describe the course of GHB withdrawal symptoms over time, (2) assess the association between vital signs and withdrawal symptoms, and (3) explore sex differences in GHB withdrawal. In this observational multicenter study, patients with GHB use disorder ( n = 285) were tapered off with pharmaceutical GHB. The most reported subjective withdrawal symptoms (SWS) were related to cravings, fatigue, insomnia, sweating and feeling gloomy. The most prevalent objective withdrawal symptoms (OWS) were related to cravings, fatigue, tremors, sweating, and sudden cold/warm feelings. No association between vital signs and SWS/OWS was found. Sex differences were observed in the severity and prevalence of specific withdrawal symptoms. Our results suggest that the GHB withdrawal syndrome under pharmaceutical GHB tapering does not strongly differ from withdrawal syndromes of other sedative drugs. The lack of association between vital signs and other withdrawal symptoms, and the relative stability of vitals over time suggest that vitals are not suitable for withdrawal monitoring. The reported sex differences highlight the importance of a personalized approach in GHB detoxification.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7-25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.

In the past decades, monitoring programs have been developed for healthcare professionals with substance use disorders. We aimed to explore estimates of abstinence and work retention rates after participation in such monitoring programs. A literature search was performed using PubMed, Embase, PsycINFO, and CINAHL. Twenty-nine observational studies reporting on success rates (abstinence and work retention) of monitoring for healthcare professionals with a substance use disorder were included in the meta-analysis. Quality-effects models calculated pooled success rates and corresponding 95%-Confidence Intervals (CI), with subgroup analyses on monitoring elements and patient characteristics. Pooled success rates were 72% for abstinence (95%-CI = 63-80%) and 77% for work retention (95%-CI = 61-90%). Heterogeneity across studies was partly explained by the starting moment of monitoring, showing higher abstinence rates for studies that started monitoring after treatment completion (79%; 95%-CI = 72-85%) compared to studies that started monitoring with treatment initiation (61%; 95%-CI = 50-72%). About three-quarters of healthcare professionals with substance use disorders participating in monitoring programs are abstinent during follow-up and working at the end of the follow-up period. Due to selection and publication bias, no firm conclusions can be drawn about the effectiveness of monitoring for healthcare professionals with SUD.

Unprotected sexual contact continues to be a main cause of HIV transmission and poses certain key populations at increased risk for HIV infection. One of the populations at high risk are men who have sex with men. A subset of MSM engages in chemsex, whereby consumption of illicit drugs is used to facilitate or enhance sexual activity. This practice can have several negative consequences, such as sexually transmitted infections (including HIV) and mental health problems (including compulsive sexual behavior, addiction, and mood disorders). In this article, we provide our perspective on the current situation that medical professionals dealing with MSM living with HIV often feel empty-handed in how to deal with these behavioral and psychological issues. Close collaboration between somatic and mental health professionals is key to address treatment needs of people living with HIV, regarding the negative consequences of chemsex and their overall quality of life. In this article, we discuss possibilities for psychological treatment, including behavioral skills training to improve impulse control and reduce compulsive sexual behaviors among MSM living with HIV who persistently engage in sexual transmission risk behavior, based on our experience with implementing such an intervention. Important barriers and facilitators for further implementation of behavioral interventions will be discussed. Reduction of HIV transmission risk behavior is needed to achieve the WHO aim to end HIV as a public health threat by 2030. We propose that close collaboration between somatic and mental health professionals and implementation of behavioral interventions for risk populations are key to achieve this goal., (Copyright © 2020 Arends, van den Heuvel, Foeken-Verwoert, Grintjes, Keizer, Schene, van der Ven and Schellekens.)

Background: Alcohol Use Disorder (AUD) and depressive disorder often co-exist and have a shared heritability. This study aimed to investigate Brain-Derived Neurotrophic Factor (BDNF) and three Cell Adhesion Molecules (CAMs) as transdiagnostic biomarkers in AUD and depression co-morbidity., Methods: In a cross-sectional study, patients with AUD (n=22), AUD and depression (n=19), and healthy controls (n=20) were examined. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Anhedonia, alcohol use and dependence, craving, and social adaptation were assessed through self-report questionnaires. BDNF and CAM concentrations in peripheral serum were measured after overnight fasting using a Luminex assay. After controlling for age and gender, biomarker levels were compared across groups. The association between biomarker concentrations and symptom severity scales were explored using correlation and multiple regression analyses., Results: BDNF and Neuronal CAM were lower in patients with AUD with and without depression compared to healthy controls. No differences were observed for Vascular CAM-1 and Interstitial CAM-1. BDNF correlated negatively with anhedonia levels. BDNF, age and gender together explained 21% of variability in anhedonia levels., Conclusion: This pilot study suggests that peripheral levels of BDNF and NCAM might be reduced in AUD with and without comorbid mood disorder. Since low BDNF levels were associated with self- reported anhedonia across these conditions, BDNF and anhedonia might reflect transdiagnostic aspects involved in AUD and depression., (Copyright © 2020 Levchuk, Meeder, Roschina, Loonen, Boiko, Michalitskaya, Epimakhova, Losenkov, Simutkin, Bokhan, Schellekens and Ivanova.)

HIV, hepatitis B and C, and syphilis share common transmission routes of which primarily unsafe sexual contact and injecting drug use are important. Impulsivity is a major factor contributing to this transmission risk behavior; however comprehensive studies within female, prison, and Asian populations are scarce. This cross-sectional study aims to delineate the contributions of different aspects of impulsivity to risk behavior, among female inmates living in a prison in Jakarta (N = 214). The relationships between various aspects of impulsivity, risk behaviors and seropositivity were tested using analyses of variance and logistic regression analyses. Motor impulsivity was related to alcohol use, reward-related impulsivity to drug use, and cognitive/goal-directed impulsivity to sexual risk behavior. Finally, goal-directed impulsivity was also directly associated with seropositivity. Specific aspects of impulsivity are associated with different types of risk behavior in Indonesian female prisoners, which can be relevant for future studies on infection prevention strategies for such a population., Competing Interests: The authors have declared that no competing interests exist.

Efavirenz is recommended as a preferred first-line drug for women of childbearing potential living with human immunodeficiency virus. Efavirenz is known for its central nervous system side effects, which are partly mediated by serotonergic actions. The neurotransmitter serotonin exerts neurotrophic effects during neurodevelopment and antenatal exposure to serotonergic agents has been linked to developmental delay. Although the teratogenic risks of efavirenz appear to be minimal, data on long-term developmental effects remain scarce. Here, we aimed to investigate the short- and long-term behavioral and neurodevelopmental effects of perinatal efavirenz exposure. We treated pregnant rats from gestation day 1 until postnatal day 7 with efavirenz (100 mg/kg) or vehicle. We measured behavioral outcomes in male offspring during the first 3 postnatal weeks, adolescence and adulthood, and conducted brain immunohistochemistry analyses after sacrifice. Perinatal efavirenz exposure resulted in reduced body weight and delayed reflex and motor development. During adulthood, we observed a decrease in the total number of cells and mature neurons in the motor cortex, as well as an increase in the number of Caspase-3-positive cells and serotonergic fibers. Together, our data show a developmental delay and persistent changes in the brain motor cortex of rats exposed to efavirenz perinatally. Because over 1 million children born annually are exposed to antiretroviral therapy, our findings underline the need for clinical studies on long-term neurodevelopmental outcomes of perinatal exposure to efavirenz.

Short Summary: : In this study in healthy moderate alcohol consumers, we observe that one month of alcohol abstinence results in decreased gamma-glutamyl transferase levels, which return to baseline levels after resumption of alcohol consumption.