Parental bonding style and illness severity in a longitudinal study of individuals with first episode psychosis.

A parenting style with high amounts of control combined with low caring or nurturing behaviour has been reported in association with mental disorders including schizophrenia. However, the association of parenting style with illness severity in individuals with schizophrenia has never been evaluated retrospectively or over a longitudinal time course. In a subset (n = 84) of the participants included in the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses)-10 study, we evaluated participants' perceptions of their own parents' bonding style at the time of their first episode of psychosis using the parental bonding instrument (PBI). We then examined the association between different bonding styles, illness course and severity, and global functioning over a 10-year follow-up. Participants who perceived that their fathers had a more caring and less controlling parenting style showed better functioning at follow-up. However, in contrast to previous research, participants who reported having been subject to uncaring and controlling parenting styles were not found to have a notably worse course of illness or symptom severity over the follow-up period. These results indicate that more optimal parental bonding styles may be associated with better overall functioning in individuals with psychosis but not with other measures of illness outcome.

Rethinking the course of psychotic disorders: modelling long-term symptom trajectories.

BACKGROUND: The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach. METHOD: AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time. RESULTS: We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory. CONCLUSION: Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

The experience of widening participation students in undergraduate medical education in the UK: A qualitative systematic review.

Introduction: Most widening participation (WP) research is focused on medical school recruitment; there is a paucity of research examining whether the experience of medical school itself is an equal experience for both 'traditional' and WP students.Methods: This qualitative systematic review used the Joanna Briggs Institute (JBI) meta-aggregative approach to characterise the experience of undergraduate medical education in the UK from the perspective of WP students. Seven databases were searched, 27 studies were critically appraised, and 208 findings were grouped into 12 categories and four synthesised findings.Results: The majority of the research found relates to ethnic minority groups, with reports of other WP groups being less frequent. Whilst WP programmes attempt to alleviate disadvantages prior to entering university, our findings suggest that difficulties follow WP students into medical school. Unfamiliarity with higher education and lack of representation of WP staff in faculty can deter help-seeking behaviour and result in lack of trust. Furthermore, students from different backgrounds can find their identity conflicted upon entering medical school. Despite difficulties in establishing social networks with 'traditional' medical student peers, WP students form strong relationships with students from similar backgrounds.Conclusions: Ultimately, these students find that the uniqueness of their experience is a useful tool for communicating with diverse patients which they come across and are able to overcome adversity with the help of a supportive institution.

Diagnostic stability and outcome after first episode psychosis.

BACKGROUND: Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied. AIMS: Our aim was to examine the association between diagnostic change and later outcome. METHODS: Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression. RESULTS: Individuals always diagnosed with schizophrenia (n = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia (n = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia (n = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia (n = 44). CONCLUSIONS: Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis.

Symptom remission at 12-weeks strongly predicts long-term recovery from the first episode of psychosis.

BACKGROUND: To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis. METHODS: AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up. RESULTS: At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60-7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02-7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23-6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25-8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61-41.42). CONCLUSIONS: Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Neuropsychological function at first episode in treatment-resistant psychosis: findings from the ÆSOP-10 study.

BACKGROUND: Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis. METHODS: We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up. RESULTS: Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = -2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = -2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01-0.001) and those born outside the UK (p values<0.05). CONCLUSIONS: Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable - at a group level - at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

Ethnicity and long-term course and outcome of psychotic disorders in a UK sample: the ÆSOP-10 study.

BackgroundThe incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.AimsTo investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.MethodÆSOP-10 is a 10-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.ResultsThere was evidence that, compared with White British, Black Caribbean patients experienced worse clinical, social and service use outcomes and Black African patients experienced worse social and service use outcomes. There was evidence that baseline social disadvantage contributed to these disparities.ConclusionsThese findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.

Outcomes following first-episode psychosis - Why we should intervene early in all ages, not only in youth.

OBJECTIVE: To compare baseline demographics and 10-year outcomes of a first-episode psychosis patient incidence cohort in order to establish whether current youth-focussed age-based criteria for early intervention services are justified by patient needs. The patients in this cohort were treated prior to the establishment of early intervention services. The study aimed to test the hypothesis that those who develop psychosis at a younger age have worse outcomes than those who develop psychosis at an older age. METHODS: Data on first-episode psychosis patients from the ÆSOP-10 longitudinal follow-up study were used to compare baseline characteristics, and 10-year clinical, functional and service use outcomes between those patients who would and would not have met age-based criteria for early intervention services, in Australia or in the United Kingdom. RESULTS: In total, 58% men and 71% women with first-episode psychosis were too old to meet current Australian-early intervention age-entry criteria (χ2 = 9.1, p = 0.003), while 21% men and 34% women were too old for UK-early intervention age-entry criteria (χ2 = 11.1, p = 0.001). The 10-year clinical and functional outcomes did not differ significantly between groups by either Australian- or UK-early intervention age-entry criteria. Service use was significantly greater among the patients young enough to meet early intervention age-criteria (Australia: incidence rate ratio = 1.35 [1.19, 1.52], p < 0.001; United Kingdom: incidence rate ratio = 1.65 [1.41, 1.93], p < 0.001). CONCLUSION: Current early intervention services are gender- and age-inequitable. Large numbers of patients with first-episode psychosis will not receive early intervention care under current service provision. Illness outcomes at 10-years were no worse in first-episode psychosis patients who presented within the age range for whom early intervention has been prioritised, though these patients had greater service use. These data provide a rationale to consider extension of early intervention to all, rather than just to youth.

Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study.

It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described.

Gender differences in the association between childhood physical and sexual abuse, social support and psychosis.

PURPOSE: Childhood adversity (variously defined) is a robust risk factor for psychosis, yet the mitigating effects of social support in adulthood have not yet been explored. This study aimed to investigate the relationships between childhood sexual and physical abuse and adult psychosis, and gender differences in levels of perceived social support. METHODS: A sample of 202 individuals presenting for the first time to mental health services with psychosis and 266 population-based controls from south-east London and Nottingham, UK, was utilised. The Childhood Experience of Care and Abuse Questionnaire was used to elicit retrospective reports of exposure to childhood adversity, and the Significant Others Questionnaire was completed to collect information on the current size of social networks and perceptions of emotional and practical support. RESULTS: There was evidence of an interaction between severe physical abuse and levels of support (namely, number of significant others; likelihood ratio test χ(2) = 3.90, p = 0.048). When stratified by gender, there were no clear associations between childhood physical or sexual abuse, current social support and odds of psychosis in men. In contrast, for women, the highest odds of psychosis were generally found in those who reported severe abuse and low levels of social support in adulthood. However, tests for interaction by gender did not reach conventional levels of statistical significance. CONCLUSIONS: These findings highlight the importance of investigating the potential benefits of social support as a buffer against the development of adult psychosis amongst those, particularly women, with a history of early life stress.

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study.

BACKGROUND: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. METHODS: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases. Cognitive measures were grouped into seven cognitive domains based on the pre-existing literature. We ran multiple imputation for missing data and used logistic regression to test for associations between cognitive performance at FEP and treatment resistant status at follow-up. RESULTS: On average patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. Univariate logistic regressions showed that antipsychotic treatment resistance cases had significantly poorer IQ/general cognitive functioning at FEP (OR = 0.70, p = .003). These findings remained significant after adjusting for additional variables in multivariable analyses (OR = 0.76, p = .049). CONCLUSIONS: Although replication in larger studies is required, it appears that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance. Cognitive variables may be able to provide further insight into neurodevelopmental factors associated with treatment resistance or act as early predictors of treatment resistance, which could allow prompt identification of refractory illness and timely interventions.

Barriers and facilitators for implementation of a national recommended specialty core-curriculum across UK medical schools: a cross-sectional study using an online questionnaire.

OBJECTIVES: The National Health Service (NHS) Long-Term plan published in 2019 set out healthcare reforms to meet the healthcare demands of UK. Undergraduate specialty core-curricula like dermatology aligns well to the training needs of the future workforce but lacks representation, consistency and implementation. This study explores the barriers and facilitators influencing the implementation of a specialty-specific (dermatology) national core-curriculum across UK medical schools. DESIGN: A constructivist approach was used to develop an online questionnaire and data collected using mixed methodology. PARTICIPANTS: Undergraduate dermatology teaching leads across all UK medical schools. RESULTS: 30 out of 42 UK medical schools responded to the survey (71%). 16 out of 30 (53%) responders were unaware of the planned Medical Licensing Assessments (MLA) for all UK graduates in 2024-2025; 43% were unaware if dermatology was mapped to national standards; 50% were unsure if the dermatology was blueprinted on school curricula. Barriers to implementation included competing NHS service commitments, the specialty not seen as a priority and difficulty influencing curricula changes at school level. Facilitators included workforce planning and transparency in funding to support leadership in undergraduate education. Domains identified for curriculum implementation were: (1) awareness of the role of General Medical Council and the MLA, (2) medical education training for teaching leads, (3) lack of recognition and resources for leadership, (4) skills development to map, blueprint and assess specialty core-components, (5) medical school and specialty engagement. CONCLUSIONS: This study identifies the potential barriers and facilitators to specialty specific core-curricular implementation across UK medical schools. Lack of standardised training in medical education, time and resources undermine the role of specialty teaching leads as medical educators. Medical school engagement with specialties with mutual support would aid the forthcoming educational reforms.

Usability: An introduction to and literature review of usability testing for educational resources in radiation oncology.

Usability, or the ease with which something can be used, is a key aspect in ensuring end-users can achieve the best possible outcomes from a given educational resource. Ideally usability testing should take place iteratively throughout the design of the resource, and there are several approaches for undertaking usability testing described in the wider literature. Within radiation oncology education, the extent to which usability testing occurs remains unclear. This literature review aimed to assess current practice and provide a practical introduction to usability testing for educational resource design within radiation oncology. Two web databases were searched for articles describing planned or completed usability testing during the design of a radiation oncology educational resource. Fifteen studies were identified. Data was gathered describing the type of usability testing performed, the number of cycles of testing and the number of test subjects. Articles described design of educational resources for both patients and trainees, with the number of test subjects ranging from 8 to 18. Various testing methods were used, including questionnaires, think aloud studies and heuristic evaluation. Usability testing comprised a range of single cycle through to several rounds of testing. Through illustrative examples identified in the literature review, we demonstrate that usability testing is feasible and beneficial for educational resources varying in size and context. In doing so we hope to encourage radiation oncologists to incorporate usability testing into future educational resource design.

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia.

IMPORTANCE: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. OBJECTIVE: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. DESIGN, SETTING, AND PARTICIPANTS: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). MAIN OUTCOMES AND MEASURES: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. RESULTS: The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04). CONCLUSIONS AND RELEVANCE: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

INTRODUCTION: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. METHODS: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. RESULTS: Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). IMPLICATIONS: Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Assessment of posttraumatic symptoms in patients with first-episode psychosis.

Posttraumatic stress disorder is common among patients with psychotic disorders. The present study examined the internal reliability and comparability of the Impact of Event Scale (IES) in a sample of 38 patients with first-episode psychosis and 47 controls exposed to severe physical and/or sexual abuse. The IES total score and both subscales showed high internal consistency in both groups (Cronbach's alpha coefficients of approximately 0.9 or higher). Given their equivalent trauma reporting, the lack of differences in IES scores between patients and controls seems to indicate that patients are likely to report accurately and neither exaggerate nor minimize their posttraumatic symptoms. Overall, the findings suggest that the IES can be used to assess symptoms of posttraumatic stress in patients with psychotic disorders as in other populations.

The association between substance misuse and first-episode psychosis in a defined UK geographical area during the 1990s.

OBJECTIVE: The aim of this study was to examine the prevalence of all substance use disorders (SUD) and cannabis-specific SUDs reported in two first-episode epidemiological studies, conducted in the same catchment area, 5 years apart. METHODS: The prevalence of schizophrenia in Nottingham and Aetiology and Ethnicity of Schizophrenia and Other Psychoses studies included all people with a first-episode of psychosis between 1992 and 1994 and 1997 and 1999, respectively. Those individuals with a comorbid diagnosis of a SUD (ICD-10 harmful use or dependence) were identified. RESULTS: An upward (but not statistically significant) trend in all SUDs was found for the first-episode study population as a whole, between the two cohorts (11.9-18.2%). When analysed by age, a significant increase in cannabis-specific SUDs was observed for all first-episode cases aged 16-29 between cohorts (3.2-10.6%). When analysed by age and gender, a significant increase in all SUDs was apparent for female first-episode patients aged 16-29 between cohorts (6.1-24.2%), this same increase was not seen in male patients. CONCLUSIONS: Illegal drug misuse is common in patients with a first-episode of psychosis. However, most concerning is that when both age and gender are considered, females with a first-episode of psychosis aged 16-29 show a highly significant rise in the prevalence of all SUDs over the 1990s. More recent drug use data from England and Wales shows that the prevalence of drug use in the 21st century is declining; further epidemiological studies are required to determine whether this is also the case in young female first-episode psychosis populations.

Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study.

Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.