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Ernst L Noordraven,1,2 André I Wierdsma,2 Peter Blanken,3 Anthony F T Bloemendaal,1 Cornelis L Mulder2,4 1Dual Diagnosis Centre (CDP), Parnassia Psychiatric Institute, the Hague, 2Department of Psychiatry, Erasmus University Medical Center, Rotterdam, 3Parnassia Addiction Research Centre (PARC), Parnassia Psychiatric Institute, the Hague, 4Bavo-Europoort Mental Health Care, Parnassia Psychiatric Institute, Rotterdam, the Netherlands Background: Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Methods: Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Results: Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Conclusion: Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed. Keywords: noncompliance, psychotic disorder, illness insight, motivation, depot medication, schizophrenia

Eline C Jochems,1,2 Christina M van der Feltz-Cornelis,1–3 Arno van Dam,3,4 Hugo J Duivenvoorden,5 Cornelis L Mulder1,6 1Department of Psychiatry, Epidemiological and Social Psychiatric Research Institute, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 2GGz Breburg, Top Clinical Center for Body, Mind and Health, Tilburg, the Netherlands; 3Tilburg University, Faculty of Social Sciences, Tranzo Department, Tilburg, the Netherlands; 4GGZ Westelijk Noord Brabant, Bergen op Zoom, the Netherlands; 5Erasmus MC University Medical Center, Rotterdam, the Netherlands; 6BavoEuropoort, Parnassia Psychiatric Institute, Rotterdam, the Netherlands Objective: To evaluate the effectiveness of providing clinicians with regular feedback on the patient’s motivation for treatment in increasing treatment engagement in patients with severe mental illness.Methods: Design: cluster randomized controlled trial (Dutch Trials Registry NTR2968). Participants: adult outpatients with a primary diagnosis of a psychotic disorder or a personality disorder and their clinicians, treated in 12 community mental health teams (the clusters) of two mental health institutions in the Netherlands. Interventions: monthly motivation feedback (MF) generated by clinicians additional to treatment as usual (TAU) and TAU by the community mental health teams. Primary outcome: treatment engagement at patient level, assessed at 12 months by clinicians. Randomization: teams were allocated to MF or TAU by a computerized randomization program that randomized each team to a single treatment by blocks of varying size. All participants within these teams received similar treatment. Clinicians and patients were not blind to treatment allocation at the 12-month assessment.Results: The 294 randomized patients (148 MF, 146 TAU) and 57 clinicians (29 MF, 28 TAU) of 12 teams (6 MF, 6 TAU) were analyzed according to the intention-to-treat principle. No statistically significant differences between treatment groups on treatment engagement were found (adjusted mean difference =0.1, 95% confidence interval =-2.2 to 2.3, P=0.96, d=0). Preplanned ancillary analyses showed statistically significant interaction effects between treatment group and primary diagnosis on treatment motivation and quality of life (secondary outcomes), which were beneficial for patients with a primary diagnosis of a personality disorder but not for those with a psychotic disorder. There were no reports of adverse events.Conclusion: The current findings imply that monitoring and discussing the patient’s motivation is insufficient to improve motivation and treatment engagement, and suggests that more elaborate interventions for severe mental illness patients are needed. Keywords: randomized controlled trial, feedback, motivation, adherence, psychotic disorders, personality disorders

Clazien Bouwmans,1 Caroline de Sonneville,1 Cornelis L Mulder,2,3 Leona Hakkaart-van Roijen11Institute for Medical Technology Assessment, Erasmus University Rotterdam, 2Epidemiological and Social Psychiatric Research Institute, Erasmus Medical Center, 3Parnassia Psychiatric Institute, Rotterdam, the NetherlandsAbstract: A systematic review was conducted to assess the employment rate of people with schizophrenia. Additionally, information from the selected studies concerning factors associated with employment and health-related quality of life (HRQoL) was examined. Employment rates ranged from 4% to 50.4%. The studies differed considerably in design, patient settings, and methods of recruitment. The most frequently reported factors associated with employment were negative and cognitive symptoms, age of onset, and duration and course of the disease. Individual characteristics associated with unemployment were older age, lower education, and sex (female). Additionally, environmental factors, eg, the availability of welfare benefits and vocational support programs, seemed to play a role. Generally, being employed was positively associated with HRQoL. However, the causal direction of this association remained unclear, as studies on the bidirectional relationship between employment and HRQoL were lacking.Keywords: health-related quality of life, employment, work, unemployment, mental illness, patient characteristics, environment

Abstract Background Crises and (involuntary) admissions have a strong impact on patients and their caregivers. In some countries, including the Netherlands, the number of crises and (involuntary) admissions have increased in the last years. There is also a lack of effective interventions to prevent their occurrence. Previous research has shown that a form of psychiatric advance statement – joint crisis plan – may prevent involuntary admissions, but another study showed no significant results for another form. The question remains which form of psychiatric advance statement may help to prevent crisis situations. This study examines the effects of two other psychiatric advance statements. The first is created by the patient with help from a patient's advocate (Patient Advocate Crisis Plan: PACP) and the second with the help of a clinician only (Clinician facilitated Crisis Plan: CCP). We investigate whether patients with a PACP or CCP show fewer emergency visits and (involuntary) admissions as compared to patients without a psychiatric advance statement. Furthermore, this study seeks to identify possible mechanisms responsible for the effects of a PACP or a CCP. Methods/Design This study is a randomised controlled trial with two intervention groups and one control condition. Both interventions consist of a crisis plan, facilitated through the patient's advocate or the clinician respectively. Outpatients with psychotic or bipolar disorders, who experienced at least one psychiatric crisis during the previous two years, are randomly allocated to one of the three groups. Primary outcomes are the number of emergency (after hour) visits, (involuntary) admissions and the length of stay in hospital. Secondary outcomes include psychosocial functioning and treatment satisfaction. The possible mediator variables of the effects of the crisis plans are investigated by assessing the patient's involvement in the creation of the crisis plan, working alliance, insight into illness, recovery style, social support, locus of control, service engagement and coping with crises situations. The interviews take place before randomisation, nine month later and finally eighteen months after randomisation. Discussion This study examines the effects of two types of crisis plans. In addition, the results offer an understanding of the way these advance statements work and whether it is more effective to include a patients' advocate in the process of creating a psychiatric advance statement. These statements may be an intervention to prevent crises and the use of compulsion in mental health care. The strength and limitations of this study are discussed. Trial registration Current Controlled Trails NTR1166.

OBJECTIVE: This study examined whether employing mental health consumers as consumer-providers in assertive community treatment teams can enhance outcomes for clients with severe mental illness. METHODS: In a prospective longitudinal study, presence of consumer-providers and outcomes of 530 clients with severe mental illness in 20 outpatient teams were assessed at baseline and at one-year and two-year follow-ups. Measures included the Health of the Nation Outcome Scales (HoNOS), the Camberwell Assessment of Need Short Assessment Schedule (CANSAS), the Working Alliance Scale, the number of hospital days, and the number of days of homelessness. Multilevel regression was used with the independent variables consumer-provider presence, time of measurement, and their interaction. RESULTS: A positive association was found between consumer-provider presence and improvements in functioning on the HoNOS (p=.020), met needs in relation to personal recovery (p=.044), unmet needs in relation to personal recovery (p=.008), and number of homeless days (p.001). A negative association was found for consumer-provider presence and the number of hospital days (p=.019). CONCLUSIONS: Consumer-providers are important participants in outpatient teams serving clients with severe mental illnesses, although integrating these providers as part of a team is a slow process. (Psychiatric Services 63:477-481, 2012; doi: 10.1176/appi.ps.201000549). [ABSTRACT FROM AUTHOR]

Introduction: Psychiatric intensive care units (PICU) are small wards, designed for the most difficult-to-manage patients. They have higher levels of nursing and other staff, are often locked, and sometimes have facilities for seclusion. Although PICU staff are often confronted with aggressive behavior, resulting in higher usage of coercive measures, there is need to increase understanding of the necessary infrastructure and treatment policy for successfully reducing seclusion and restraint. Aim: To investigate whether patients transferred to a newly developed PICU, focused on the effective and non-coercive management of disruptive behavior, are secluded and restrained less than during earlier stays in a psychiatric unit. Method: The effect of the newly developed PICU on reducing seclusion was evaluated in eight patients, six of whom had been diagnosed with a severe form of borderline personality disorder. The number of days in seclusion during the period before admission to the PICU was compared to the number of days in seclusion after admission to the PICU. Results: After patients' admission to PICU, the use of seclusion was almost completely eliminated, falling from 40% of admission days spent in seclusion before transfer to the PICU to 0.1% during their stay at the PICU. Conclusion: When a special non-coercive infrastructure and treatment policy is applied at a PICU, seriously disturbed patients can be treated without coercive measures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mental health problems often emerge in young adulthood. Although effective treatments are available, young adults are unlikely to seek professional help. This study examined barriers-to-care in young adults with serious internalizing or externalizing problems. METHODS: Population-based study among 2258 19-32-year olds in the south-west region of the Netherlands. Barriers-to-care were examined in participants with serious internalizing or externalizing problems who did not seek professional help. A potential barrier was that participants denied that they had mental health problems. In those admitting problems, barriers were assessed with the Barriers-to-Care checklist and analyzed with Latent Class Analysis. RESULTS: Of 362 participants with serious internalizing or externalizing problems 237 (65.5%) did not seek professional help. Of non-help-seeking young adults 36% denied having problems; additionally Latent Class Analysis revealed that 37% Perceived Problems as Self-Limiting (e.g., they believed that problems were not serious) and 24% Perceived Help-Seeking Negatively (e.g., they believed that treatment would not help). CONCLUSIONS: Young adults' barriers-to-care reflect limitations in their knowledge of mental health problems and available treatments, but possibly also a failure of existing mental health services to engage young people. More knowledge is urgently needed about the effectiveness of mental health treatments for young adults specifically. PRACTICE IMPLICATIONS: Treatment accessibility for young adults may be augmented by improving their mental health literacy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Psychotic disorders are more common in people from ethnic minorities. If psychosis exists as a continuous phenotype, ethnic disparities in psychotic disorder will be accompanied by similar ethnic disparities in the rate of psychotic symptoms. This study examined ethnic disparities in self-reported hallucinations in a population sample of young adults.MethodA cross-sectional population survey (n=2258) was carried out in the south-west Netherlands. Seven ethnic groups were delineated: Dutch natives, Turks, Moroccans, Surinamese/Antilleans, Indonesians, other non-Western immigrants (mostly from Africa or Asia) and Western immigrants (mostly from Western Europe). Self-reported auditory and visual hallucinations were assessed with the Adult Self-Report (ASR). Indicators of social adversity included social difficulties and a significant drop in financial resources. RESULTS: Compared to Dutch natives, Turkish females [odds ratio (OR) 13.48, 95% confidence interval (CI) 5.97-30.42], Moroccan males (OR 8.36, 95% CI 3.29-21.22), Surinamese/Antilleans (OR 2.19, 95% CI 1.05-4.58), Indonesians (OR 4.15, 95% CI 1.69-10.19) and other non-Western immigrants (OR 3.57, 95% CI 1.62-7.85) were more likely to report hallucinations, whereas Western immigrants, Turkish males and Moroccan females did not differ from their Dutch counterparts. When adjusting for social adversity, the ORs for self-reported hallucinations among the non-Western immigrant groups showed considerable reductions of 28% to 52%. CONCLUSIONS: In a general population sample, several non-Western immigrant groups reported hallucinations more often than Dutch natives, which is consistent with the higher incidence of psychotic disorders in most of these groups. The associations between ethnicity and hallucinations diminished after adjustment for social adversity, which supports the view that adverse social experiences contribute to the higher rate of psychosis among migrants. [ABSTRACT FROM AUTHOR]

Objective: Aims of the study were to assess, among clients receiving an outpatient treatment program (OTP), whether female crack abusers have more severe problems and/or different service needs than men.Methods: A total of 63 chronic crack abusers (34 women) participated in the study at baseline. Follow-up data were available for 33 subjects (21 women). Outcome measures included general condition at intake, and treatment compliance, outcome and satisfaction. Data were collected by means of monthly registrations, EuropAsi interviews and an evaluation form. OTP consisted of assertive outreach, a time-out provision, and intensive case management.Results: The vast majority of women were involved in street prostitution and were extremely vulnerable to deterioration. Compared to men, women who entered treatment had poorer physical health, higher rates of previous physical/sexual abuse, and more anxiety symptoms. Women reported a longer episode of cocaine abstinence than men. At discharge from OTP men reported a significantly better treatment outcome than women. Both genders gained most improvement in general living conditions. No gender differences emerged in treatment compliance. Although both men and women were satisfied with the service items offered by OTP, an outpatient walk-in service best served the needs of men, whereas women preferred a 24-hour care service including medical treatment and motivational outreach.Conclusions: Due to the harshness of street prostitution, treatment for female crack abusers should address areas of severe impairment. Integrated treatment services, tailored to the lifestyle of these women, are required to improve their general situation and safety. [ABSTRACT FROM AUTHOR]

Over the past two decades, advances in cancer therapy have significantly improved survival rates, particularly in childhood cancers. Still, many treatments pose a substantial risk for diminishing future fertility potential due to the gonadotoxic nature of many cancer regimens, justifying fertility preservation programs for both childhood and adult cancer patients. To assure a balance between offering fertility preservation and actual chance of infertility post-treatment, guidelines are in place. However, assessing the actual risk of infertility after treatment remains challenging, given the multi-faceted approach of many cancer treatment plans, which are continuously evolving. This review discusses the evolution of cancer therapy over the past 20 years and attempts to assess their impact on fertility after treatment. Overall, cancer regimens have shifted from broadly killing fast dividing cells to more targeting therapies, reducing collateral damage in general. Although progress has been made to reduce overall toxicity, unfortunately this does not automatically translate to reduced gonadotoxicity. Therefore, current fertility preservation programs continue to be an important part of cancer care., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To compare psychotic-like experiences (PLEs) in adolescents and young adults referred to the Mental Health Services (MHSs)., Methods: Participants scored the 16-item Prodromal Questionnaire (PQ-16) as part of the intake procedure. Data on the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification and demographic data were collected., Results: The PQ-16 was completed by 13 783 respondents (mean age 24.63 years, SD = 6.09; 62.6% female). Overall, the scores on the PQ-16 were not higher for adolescents (11-17 years; m = 4.84, SD = 3.62) than for young adults (18-35 years; m = 5.47, SD = 3.85). On PQ-16 item level, adolescents reported seeing and hearing things more than adults did. Across all age groups, males scored lower on the PQ-16 than females. Specifically, adolescent males scored lower than other participants. For adolescents and young adults alike, PQ-16 scores were higher for participants with borderline personality disorder, PTSD, and mood disorder than for those with other DSM classifications., Conclusions: Although help-seeking adolescents did not score higher on the PQ-16 than help-seeking young adults, more of them reported perceptual anomalies. Irrespective of age, participants with borderline personality disorder, PTSD and mood disorder scored higher on the PQ-16 than those with other DSM classifications., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Objective: Police officers are often the first responders when individuals experience a mental health crisis and typically remain responsible for transport to a psychiatric emergency department. In 2014, a psychiatric ambulance (PA) was introduced in the city of Amsterdam to take over the transport of individuals in a mental health crisis. The purpose of the PA was to use fewer restrictive measures while guaranteeing safety for both patients and personnel., Methods: A preimplementation-postimplementation design was used to assess the feasibility and utility of a single-vehicle PA service compared with police transport. Data on 498 rides were collected in the 4 months before implementation of the PA (pre-PA cohort) and on 655 rides in the 6 months after implementation (PA cohort)., Results: After PA implementation, most patients were transported by the PA (82%), and rides by police vehicle were very rare (1%). Individuals in the PA cohort had a greater transportation delay, compared with those in the pre-PA cohort, but the PA reduced use of coercive measures with no increase in the incidence of patient aggression. Among individuals in the PA cohort, hospitalization was more often voluntary than among those in the pre-PA cohort., Conclusions: Transporting emergency psychiatric patients by a special PA rather than by the police reduced the use of coercive measures during transport, kept the occurrence of aggressive incidents stable, and was associated with fewer coercive hospital admissions., Competing Interests: The authors report no financial relationships with commercial interests.

The iBerry Study, a Dutch population-based high-risk cohort (n = 1022) examines the transition from subclinical symptoms to psychiatric disorders in adolescents. Here, we present the first follow-up measurement, approximately 3 years after baseline assessment and 5 years after the screening based on self-reported emotional and behavioral problems (SDQ-Y). We give an update on the data collection, details on the (non)response, and the results on psychopathology outcomes. The first follow-up (2019-2022) had a response rate of 79% (n = 807). Our results at baseline (mean age 15.0 years) have shown the effectiveness of using the SDQ-Y to select a cohort oversampled for the risk of psychopathology. At first follow-up (mean age 18.1 years), the previously administered SDQ-Y remains predictive for selecting adolescents at risk. At follow-up, 47% of the high-risk adolescents showed significant mental health problems based on self- and parent reports and 46% of the high-risk adolescents met the criteria for multiple DSM-5 diagnoses. Compared to low-risk adolescents, high-risk adolescents had a sevenfold higher odds of significant emotional and behavioral problems at follow-up. Comprehensive assessment on psychopathology, substance abuse, psychotic symptoms, suicidality, nonsuicidal self-injury, addiction to social media and/or video gaming, and delinquency, as well as social development, and the utilization of healthcare and social services were conducted. This wave, as well as the ones to follow, track these adolescents into their young adulthood to identify risk factors, elucidate causal mechanisms, and discern pathways leading to both common and severe mental disorders. Results from the iBerry Study will provide leads for preventive interventions., (© 2024. The Author(s).)

Background: Verbal and physical violence in psychiatric hospitals can have harmful consequences for staff members, such as physical injury, traumatisation, and sick leave, and they often accompany involuntary admission. Harm to others may co-occur with self-harm, i.e., dual harm. However, little is known about the association between dual-harm and violent behaviour towards staff members and its clinical outcomes, such as seclusion and rapid tranquilisation after involuntary admission to a psychiatric inpatient unit., Method: A convenience sample of patients admitted involuntarily (N = 384; mean age = 48.03, SD = 19.92) between January 2016 and December 2019 in Western Brabant, the Netherlands, was used to design a retrospective file audit. Distinct harm groups, marked by the presence/absence of self- and/or other-harm, were investigated using multivariate linear regression modelling on the seriousness of violent acts and the total length of admission. Logistic regression analyses were used to study the association between harm groups and the administration of rapid tranquilisation, seclusion, and extended involuntary admissions., Results: Several harm groups were identified, including self-harm only, other-harm only, and dual-harm groups. Psychiatric patients admitted to the hospital because of (the risk of) violence towards others had a higher risk of violent incidents during admission and some restrictive measures. In a subgroup of patients with psychotic disorders, patients with dual harm committed the most serious violent incidents compared to those in the other harm groups., Conclusion: Distinct harm groups were identified in a sample of involuntarily admitted patients. In a general adult psychiatric setting, patients at risk for violent behaviour, especially dual-harm patients, should be identified and monitored as part of the risk assessment. Future research is needed to explore more clinical correlates in the proposed distinction between harmful groups and to assess long-term prognosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Hypothesis: In schizophrenia spectrum disorders (SSD) personal recovery and subjective quality of life (S-QOL) are crucial and show conceptual overlap. There is limited knowledge about how these outcomes change over time. Therefore, we investigated changes in personal recovery or S-QOL for patients with SSD. We specifically focused on the influence of the patients' durations of illness (DOI) on changes in personal recovery and S-QOL., Study Design: We included 46 studies investigating longitudinal changes in quantitative assessments of personal recovery or S-QOL for patients with SSD. Outcomes were categorized in overall personal recovery, overall S-QOL connectedness, hope and optimism, identity, meaning in life, and empowerment. We evaluated effect sizes of change between baseline and follow-up assessments. We also evaluated potential moderating effects, including DOI on these changes in outcomes., Study Results: We found small improvements of overall personal recovery and S-QOL, but marginal or no improvement over time in the other more specific outcome domains. Patients without a schizophrenia diagnosis, a younger age, and more recent publications positively influenced these changes. We found no significant influence of DOI on the changes in any outcome domain., Conclusions: Improvement in personal recovery or S-QOL of people with SSD is modest at best. However, these studies did not fully capture the personal narratives or nonlinear process of recovery of an individual. Future research should focus on how to shift from a clinical to more person-oriented approach in clinical practice to support patients in improving their personal process of recovery., Review Protocol Registration: CRD42022377100., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

The quest for how to deal with a crisis in a community setting, with the aim of deinstitutionalizing mental health care, and reducing hospitalization and coercion, is important. In this article, we argue that to understand how this can be done, we need to shift the attention from acute moments to daily uncertainty work conducted in community mental health teams. By drawing on an empirical ethics approach, we contrast the modes of caring of two teams in Utrecht and Trieste. Our analysis shows how temporality structures, such as watchful waiting, are important in dealing with the uncertainty of a crisis.

Background: Research on childhood adversity and psychopathology has begun investigating the dimension of timing, however the results have been contradictory depending on the study population, outcome and how adverse life events (ALEs) were operationalized. Additionally, studies so far typically focus only on a narrow range of psychiatric diagnoses or symptoms. The current cross-sectional study aimed to examine the association between timing, type and chronicity of ALEs and adolescent mental health problems., Methods: Adolescents from a population-based cohort oversampled on emotional and behavioral problems (mean age 14.8; range 12-17, N = 861) were included in the current analysis. Primary caregivers were interviewed on what ALEs adolescents experienced. ALEs were defined in two ways: (1) broad operationalization, including school difficulties, parental divorce, and family sickness; and (2) physically threatening abuse only, including physical and sexual violence. After looking at lifetime ALEs, we turned to chronicity, timing and sex differences. We focused on overall psychiatric symptoms as well as specific domains of emotional and behavioral problems, assessed using the Youth Self Report (YSR) and psychotic experiences assessed using the Prodromal Questionnaire-16 (PQ-16). A series of linear models adjusted for sociodemographic and parental factors were used., Results: Lifetime ALEs were associated with all types of psychopathology, with relatively bigger effect sizes for broad than for physical ALEs. The latter associations were found to be more robust to unmeasured confounding. The 9-12 age period of experiencing both broad and physical ALE's was most saliently associated with any psychopathology. Girls were more at risk after experiencing any ALEs, especially if the adversity was chronic or ALEs took place after the age of 12., Conclusions: Broad as well as physical ALEs are associated with psychopathology, especially ALEs experienced during the 9-12 age period. Physical ALEs may be more useful in investigating specific etiological factors than broad ALEs. Sex differences may not emerge in lifetime measures of ALEs, but can be important for chronic and later childhood adversity., (© 2024. The Author(s).)

Introduction: Chronic alcohol-related myopathy presents with proximal muscle weakness. We studied the effect of vitamin D supplementation on muscle weakness in adults with alcohol use disorder., Method: Randomized controlled trial. Participants were community-dwelling adults with alcohol use disorder. Participants allocated to VIDIO, vitamin D intensive outreach, received bimonthly oral doses of 50,000‒100,000 IU cholecalciferol for 12 months. Participants allocated to CAU, care as usual, received prescriptions of once-a-day tablets containing 800 IU cholecalciferol and 500 mg calcium carbonate. Data included demographic variables, laboratory tests, alcohol use, and rating scales of help-seeking and support. Main outcomes were the participants' quadriceps maximum voluntary contractions (qMVC) and serum-25(OH)vitamin D concentrations, 25(OH)D., Results: In 66 participants, sex ratio 50/16, mean age 51 year, alcohol use was median 52 [IQR 24‒95] drinks per week. Baseline qMVC values were 77% (SD 29%) of reference values. Laboratory tests were available in 44/66 participants: baseline 25(OH)D concentrations were 39.4 (SD 23.7) nmol/L. Thirty-one participants with 25(OH)D concentrations <50 nmol/L received either VIDIO or CAU and improved in qMVC, respectively with mean 51 (P<0.05) and 62 Newton (no P-value because of loss of follow-up) after one year of treatment. Vitamin D status increased with mean +56.1 and +37.4 nmol/L, respectively in VIDIO and CAU., Conclusion: The qMVC values improved during vitamin supplementation in adults with vitamin D deficiency and alcohol use disorder. Despite higher 25(OH)D concentrations in VIDIO, in terms of muscle health no advise could be given in favor of one vitamin strategy over the other., Trial Registration: Netherlands Trial Register (NTR) identifier: NTR4114., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Frontline staff in psychiatry need to perform at a very high professional level in order to ensure patient and community safety. At the same time they are exposed to high levels of stress and workplace trauma. This may have severe consequences for their professional quality of life. In addition, health care workers in general have higher incidence levels of childhood adversity than the general population. The CRITIC (CRITical Incidents and aggression in Caregivers) Study aims to improve increased understanding of the interaction between personal life history (childhood adversity and benevolence), individual capabilities, exposure to trauma and violence at work and Professional Quality of Life (ProQOL)., Method: The Critic Study is a cross-sectional survey of these aspects in frontline, treatment and administrative staff in clinical and forensic psychiatry. We aim to include 360 participants. Participants will be asked to complete questionnaires on childhood adversity and childhood benevolence (assessing personal life history), professional quality of life, current trauma and violence exposure, current mental health (depression, anxiety and stress), coping, social support, work engagement and resilience. In this study we will examine the moderating role of adverse and benevolent childhood experiences in the association between workplace trauma exposure and professional quality of life. Finally, a theoretical model on the relationships between trauma, stress and coping in the context of professional functioning will be tested using structural equation modelling., Discussion: The CRITIC study examines which factors influence the complex relationship between childhood adversity and benevolence, and ProQOL in healthcare workers. It also aims to provide insight into the complex relationship between personal life history, individual characteristics, exposure to trauma and violence at work and ProQOL. The results can be used for designing interventions to increase resilience to trauma and to improve professional quality of life among health care professionals., Trial Registration: The CRITIC study has been approved by the Medical Ethical Committee of the Erasmus Medical Centre, under trial registration number NL73417.078.20., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bloemendaal, Kamperman, Bonebakker, Kool, Olff and Mulder.)

Study Question: Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue?, Summary Answer: Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding., What Is Known Already: For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established., Study Design Size Duration: A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022., Participants/materials Setting Methods: Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis., Main Results and the Role of Chance: Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm 3 with the remainder preserving fragments sized 6-20 mm 3 . Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres., Limitations Reasons for Caution: While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre., Wider Implications of the Findings: Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients., Study Funding/competing Interests: K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation-Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB&#95;SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G., N.N., S.S., C.L.M., A.M.M.v.P., C.E., R.T.M., K.D., M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests., Trial Registration Number: N/A., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Introduction: Autologous transplantation of spermatogonial stem cells (SSCs) isolated from cryopreserved testicular biopsies obtained before oncological treatment could restore fertility in male childhood cancer survivors. There is a clear necessity for in vitro propagation of the limited SSCs from the testicular biopsy prior to transplantation due to limited numbers of spermatogonia in a cryopreserved testicular biopsy. Still, there is no consensus regarding their optimal culture method. Methods: We performed a systematic review and meta-analysis of studies reporting primary testicular cell cultures of human and non-human primate origin through use of Pubmed, EMBASE, and Web of Science core collection databases. Of 760 records, we included 42 articles for qualitative and quantitative analysis. To quantify in vitro spermatogonial propagation, spermatogonial colony doubling time (CDT) was calculated, which measures the increase in the number of spermatogonial colonies over time. A generalized linear mixed model analysis was used to assess the statistical effect of various culture conditions on CDT. Results: Our analysis indicates decreased CDTs, indicating faster spermatogonial propagation in cultures with a low culture temperature (32°C); with use of non-cellular matrices; use of StemPro-34 medium instead of DMEM; use of Knockout Serum Replacement; and when omitting additional growth factors in the culture medium. Discussion: The use of various methods and markers to detect the presence of spermatogonia within the reported cultures could result in detection bias, thereby potentially influencing comparability between studies. However, through use of CDT in the quantitative analysis this bias was reduced. Our results provide insight into critical culture conditions to further optimize human spermatogonial propagation in vitro , and effectively propagate and utilize these cells in a future fertility restoration therapy and restore hope of biological fatherhood for childhood cancer survivors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 van Maaren, Alves, van Wely, van Pelt and Mulder.)

Illness Management and Recovery (IMR) is a psychosocial intervention supporting people with serious mental illnesses. In this study, 15 IMR groups were assessed for fidelity and clinician competency to establish the implementation level of all IMR elements and explore complementarity of the IMR Treatment Integrity Scale (IT-IS) to the standard IMR Fidelity Scale. Use of the IT-IS was adapted, similar to the IMR Fidelity Scale. Descriptive statistics were applied. Implementation success of IMR elements varied widely on the IMR Fidelity Scale and IT-IS (M = 3.94, SD = 1.13, and M = 3.29, SD = 1.05, respectively). Twelve IMR elements (60%) were well-implemented, whereas eight (40%) were implemented insufficiently, including some critical cognitive-behavioral techniques (e.g., role-playing). The scales appeared largely complementary, though strongly correlated (r (13) = 0.74, p = 0.002). Providing all IMR elements adequately requires a variety of clinical skills. Specific additional training and supervision may be necessary., (© 2023. The Author(s).)

Background: Although executive functioning is often measured using performance-based measures, these measures have their limits, and self-report measures may provide added value. Especially since these two types of measures often do not correlate with one another. It thus has been proposed they might measure different aspects of the same construct. To explore the differences between a performance-based measure of executive functioning and a self-report measure, we examined their associations in patients with a psychotic disorder with the following: other neurocognitive measures; psychotic symptoms; anxiety and depression symptoms, and daily-life outcome measures., Method: This cross-sectional study consisted of baseline measures collected as part of a cohort study of people with a psychotic disorder (the UP'S study; n  = 301). The Behavioral Rating Inventory of Executive Functioning Adult version (BRIEF-A) was used to assess self-rated executive functioning, and the Tower of London (TOL) to assess performance-based executive functioning. Generalized linear models (GLM) were used with the appropriate distribution and link function to study the associations between TOL and BRIEF-A, and the other variables, including the Brief Assessment of Cognition in Schizophrenia (BACS), the Positive and Negative Symptoms Scale-Remission (PANSS-R), the General Anxiety Disorder - 7 (GAD-7), the Patient Health Questionnaire - 9 (PHQ-9) and the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Model selection was based on the Wald test., Results: The TOL was associated with other neurocognitive measures, such as verbal list learning (β = 0.24), digit sequencing (β = 0.35); token motor task (β = 0.20); verbal fluency (β = 0.24); symbol coding (β = 0.43); and a screener for intelligence (β = 2.02). It was not associated with PANNS-R or WHO-DAS scores. In contrast, the BRIEF-A was associated not with other neurocognitive measures, but with the PANSS-R (β = 0.32); PHQ-9 (β = 0.52); and GAD-7 (β = 0.55); and with all the WHODAS domains: cognition domain (β = 0.54), mobility domain (β = 0.30) and selfcare domain (β = 0.22)., Conclusion: Performance-based and self-report measures of executive functioning measure different aspects of executive functioning. Both have different associations with neurocognition, symptomatology and daily functioning measures. The difference between the two instruments is probably due to differences in the underlying construct assessed., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Published by Elsevier Inc.)

In schizophrenia spectrum disorders, improvement in symptoms varies between patients with short and long durations of illness. In this meta-analysis we provided an overview of both short- and long-term symptomatic improvement for patients with schizophrenia spectrum disorders with distinct durations of illness. We included 82 longitudinal studies assessing the course of positive, negative, depressive and disorganization symptoms. We analyzed effect sizes of change in four subgroups based on durations of illness at baseline: <2 years, 2-5 years, 5-10 years, >10 years. Potential moderators were explored using meta-regression and sensitivity analyses. Overall, we found large improvements of positive symptoms and small improvements of negative, depressive, and disorganization symptoms. Positive and disorganization symptoms improved relatively stronger for patients earlier in the course of illness, whereas negative and depressive symptoms showed modest improvement regardless of duration of illness. Improvement of symptoms was associated with higher baseline severity of positive symptoms, a younger age, a smaller subsample with schizophrenia, and, specifically for negative symptoms, higher baseline severity of depressive symptoms. Future research should focus on exploring ways to optimize improvement in negative and depressive symptoms for patients with schizophrenia spectrum disorders., Competing Interests: Declaration of competing interest All authors declare no financial relationships with commercial interest, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A robust association has been reported between childhood adverse life events (ALEs) and risky substance use in adolescence. It remains unclear, however, what the impact of type and timing of these ALEs is. We investigated the association between ALEs and substance use in adolescents. ALEs were operationalized as broad (e.g., moving, parental divorce, family sickness) or physically threatening (physical and/or sexual abuse). First, we examined lifetime ALEs, followed by an investigation into their timing. The sample consisted of 909 adolescents (aged 12-18 years) from a cohort oversampled on high levels of emotional and behavioral problems. The primary caregiver indicated which ALEs each adolescent experienced across their lifetime. Adolescents self-reported on number and frequency of substances used. Poisson and ordinal regression models were used to model the associations. The associations between lifetime ALEs and a substance used were observed only for physical ALEs (incidence rate ratio 1.18 [1.03, 1.35], p = 0.02). When investigating timing, physical ALEs after the age of 12 predicted number of substances used (IRR 1.36 [1.13, 1.63], p < .001). Recent ALEs (occurring after age 12) seem to have considerable impact on substance use. Alcohol and drugs as a coping mechanism were considered a plausible explanation for the results.

Background: Spermatogonial stem cell transplantation (SSCT) is proposed as a fertility therapy for childhood cancer survivors. SSCT starts with cryopreserving a testicular biopsy prior to gonadotoxic treatments such as cancer treatments. When the childhood cancer survivor reaches adulthood and desires biological children, the biopsy is thawed and SSCs are propagated in vitro and subsequently auto-transplanted back into their testis. However, culturing stress during long-term propagation can result in epigenetic changes in the SSCs, such as DNA methylation alterations, and might be inherited by future generations born after SSCT. Therefore, SSCT requires a detailed preclinical epigenetic assessment of the derived offspring before this novel cell therapy is clinically implemented. With this aim, the DNA methylation status of sperm from SSCT-derived offspring, with in vitro propagated SSCs, was investigated in a multi-generational mouse model using reduced-representation bisulfite sequencing., Results: Although there were some methylation differences, they represent less than 0.5% of the total CpGs and methylated regions, in all generations. Unsupervised clustering of all samples showed no distinct grouping based on their pattern of methylation differences. After selecting the few single genes that are significantly altered in multiple generations of SSCT offspring compared to control, we validated the results with quantitative Bisulfite Sanger sequencing and RT-qPCRin various organs. Differential methylation was confirmed only for Tal2, being hypomethylated in sperm of SSCT offspring and presenting higher gene expression in ovaries of SSCT F1 offspring compared to control F1., Conclusions: We found no major differences in DNA methylation between SSCT-derived offspring and control, both in F1 and F2 sperm. The reassuring outcomes from our study are a prerequisite for promising translation of SSCT to the human situation., (© 2023. The Author(s).)

Background: There is growing evidence that the COVID-19 pandemic, and its associated social distancing measures, affect adolescents' mental health. We wanted to examine whether and how the number and characteristics of adolescents' psychiatric emergency presentations have changed throughout the pandemic., Methods: We extracted data from the records of 977 psychiatric emergency consultations of adolescents aged 12- 19 who had been referred to the mobile psychiatric emergency services in Rotterdam, the Netherlands between January 1 st  2018 and January1 st  2022. Demographic, contextual, and clinical characteristics were recorded. Time-series-analyses were performed using quasi-Poisson Generalized Linear Model to examine the effect of the first and second COVID-19 lockdown on the number of psychiatric emergency consultations, and to explore differences between boys and girls and internalizing versus externalizing problems., Results: The number of psychiatric emergency consultations regarding adolescents increased over time: from about 13 per month in 2018 to about 29 per month in 2021. During the COVID-19 pandemic, the increase was tempered. In the second wave a pronounced increase of psychiatric emergencies among adolescents with internalizing problems but not with externalizing problems was found., Conclusion: Despite the reported increase of mental health problems in adolescents during the COVID-19 pandemic, we did find a smaller increase in psychiatric emergency consultations in this group then would be expected considering the overall trend. Besides changes in help-seeking and access to care, a possible explanation may be that a calmer, more orderly existence, or more parental supervision led to less psychiatric emergency situations in this age group. In the second wave the number of emergency consultations increased especially among girls with internalizing problems. While there has been a particular fall in emergency referrals of adolescents with externalizing problems since the start of the pandemic it is still too early to know whether this is a structural phenomenon. It would be important to elucidate whether the changes in emergency referrals reflect a true change in prevalence of urgent internalizing and externalizing problems in adolescents during the pandemic or a problem related to access to care., (© 2023. The Author(s).)