An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.

Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.

Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays. No HIV HLA-E peptides were identified by tandem mass spectrometry analysis of HIV-infected cells. In addition, all bioinformatically predicted HIV peptide ligands (>80) were characterized by poor complex stability. Furthermore, infected cell elimination assays using an affinity-enhanced T cell receptor bispecific targeted to a previously reported HIV Gag HLA-E epitope demonstrated inconsistent presentation of the peptide, despite normal HLA-E expression on HIV-infected cells. This work highlights the instability of the HIV HLA-E peptidome as a major challenge for drug development.

Weight Stigma and Mental and Emotional Health Among Sexual and Gender Minority Individuals: A Scoping Review.

Purpose: Weight stigma is associated with poor mental and emotional health and may be especially harmful to sexual and gender minority (SGM) individuals due to co-occurring minority stress. The literature on this topic has not been synthesized. We conducted a scoping review of the literature on weight stigma and mental and emotional health among SGM individuals to synthesize findings, highlight gaps, and identify clinical and research implications. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, we searched PubMed, CINAHL, PsycINFO, and Scopus in April 2022. Included studies examined the relationship between weight stigma and mental and emotional health among SGM people of any age. We did not restrict study design or publication date. Results: Of 513 records identified, 23 met inclusion criteria. Most focused on sexual minority individuals; one focused specifically on gender minority individuals. Weight stigma was associated with poorer mental and emotional health in nearly all studies. The most common outcomes examined were self-esteem, maladaptive eating, and depressive symptoms. Five studies, all using the same dataset, focused on adolescents; none focused on older adults. Conclusions: Weight stigma is associated with poorer mental and emotional health among SGM individuals and, through its intersections with minority stress, might impact SGM individuals differently than their cisgender and heterosexual counterparts. There are important gaps regarding weight stigma's effect on SGM adolescents and gender minority individuals and its relationship with a broader range of mental and emotional health outcomes.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Group-Based Medical Mistrust in Adolescents With Poorly Controlled Asthma Living in Rural Areas.

Black youth and rural adolescents are two groups who experience asthma disparities. Racism and discrimination in health care likely lead to group-based (systems-level) medical mistrust for some adolescents. Group-based medical mistrust, one pathway by which racism drives health inequities, is associated with poorer outcomes for patients with chronic conditions. Despite its potential importance in adolescent asthma, previous research has not considered group-based medical mistrust in this population. To fill this gap, we characterize group-based medical mistrust among rural adolescents with poorly controlled asthma, examining demographic differences. We analyzed baseline data from a school-based clinical trial in which 164 adolescents (mean age = 16.3; 76.2% Black) completed the Group-Based Medical Mistrust Scale (GBMMS). Using linear regression, we tested associations with race, gender, and age, controlling for recent medical visits and insurance status. The total GBMMS mean score was 2.3 (SD = 1.22); subscale scores ranged from 2.3 to 2.4. Black adolescents reported significantly higher total GBMMS scores (ß = .45, p = .003) and significantly higher scores on two GBMMS subscales: suspicion of health care providers (ß = .56, p = .007) and lack of support from health care providers (ß = .36, p = .007). Gender and age were not associated with GBMMS scores. Health care providers need to consider medical mistrust and its role in their clinical care. Together with their institutions, health care providers and researchers should work toward changing systems that perpetuate racism to build trust as a means of reducing asthma disparities among adolescents.

Staged Cement Injections for Massive Sacral Hemangioma.

Vertebral hemangiomas are typically asymptomatic; however, they can also be a source of severe axial back pain. In this report, the authors describe the case of an unusually large sacral hemangioma that was effectively treated with staged cement augmentation. A 57-year-old man presented with chronic mid-sacral pain that was episodically severe. Magnetic resonance imaging revealed a massive lytic defect involving a majority of the body of S1 with features consistent with a hemangioma. It was theorized that the patient's pain could be attributed to the compromised structural integrity of the proximal sacrum with associated microfractures. Extensive conservative treatment failed to ameliorate the pain. A cement augmentation procedure was therefore recommended to stabilize the proximal sacrum. Due to concern about the potential for cement embolic complications, a staged bilateral approach was chosen. In the first procedure, 12 mL of bone cement was injected into the right proximal sacrum. The pain was partially improved by this injection. A 2-month interval was observed before the second cement injection in order to give time for pulmonary recovery from any potential microscopic emboli. In the second stage, 8 mL of bone cement was injected into the left proximal sacrum with excellent pain relief. There were no complications from either injection. At the 5-year follow-up, the patient reported no recurrence of mid-sacral pain. To the authors' knowledge, this is the first case reporting the effective treatment of a sacral hemangioma with staged cement injections. [Orthopedics. 2023;46(4):e253-e256.].

Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Is C7-T1 cervical disc replacement a viable technique: A case series.

INTRODUCTION: Cervical disc replacement (CDR) surgery is well established for the treatment of disc degeneration from C3-C7, but there is little data regarding the safety and efficacy of CDR at the cervicothoracic junction, C7-T1. CDR is an appealing option, in terms of range of motion preservation, symptom relief, and absence of risk for nonunion. Currently, C7-T1 CDR is not approved by the Food and Drug Administration, and the existing literature is limited to two case reports that describe the results of a combined two patients. This series explores whether C7-T1 CDR is a reasonable treatment and alternative to fusion. METHODS: We present a case series of seven consecutive patients who underwent CDR at C7-T1 by a single surgeon from January to December of 2019. There were five females and two males with an average age of 61.3 ± 6.4 years. RESULTS: Average follow up was 18.9 ± 2.5 months. The average postoperative NDI score was 22.6 % ± 14.0. We also recorded qualitative data regarding patient satisfaction and revision surgery status. There was one complication of disc subsidence following three months of complete pain resolution. The six other patients reported being very satisfied with their surgical outcome. CONCLUSION: These seven cases dramatically increase the volume of data in the literature on clinical outcomes and patient satisfaction following CDR at the cervicothoracic junction. Additionally, the heterogeneity of cases shows the effectiveness of this treatment in many real-world cases. A greater volume of cases with longer follow up will be necessary to better establish long-term clinical success.

Asthma Knowledge, Self-Efficacy, and Self-Management Among Rural Adolescents with Poorly Controlled Asthma.

Rural adolescents with asthma are a disparate group. Self-management is essential to asthma control. We describe asthma knowledge, self-efficacy, and self-management behaviors among 198 rural adolescents with poorly controlled asthma, exploring demographic differences; we also test the application of Social Cognitive Theory to asthma self-management examining if self-efficacy mediates associations between knowledge and self-management. Asthma knowledge and self-management were relatively poor in our sample, particularly among male and White adolescents; greater knowledge was significantly associated with better symptom prevention and management. Self-efficacy partially mediated the association between knowledge and symptom prevention, but not acute symptom management, suggesting that knowledge may not improve symptom prevention behaviors without confidence to implement such behaviors and that factors beyond knowledge and self-efficacy likely play a role in asthma self-management in this population. Addressing asthma knowledge and self-efficacy could improve self-management and, ultimately, enhance asthma control among rural adolescents with poorly controlled asthma.

Characteristics of People Returned to Prison From Medium Secure Psychiatric Services in England and Wales: National Cohort Study.

Background: Little is known about people who are admitted to medium secure services (MSSs) from prison, including characteristics and factors that influence clinical pathways and subsequent discharge. We recently published the first study to establish the circumstances by which MSS "prison-transfer" patients are returned to prison. Of particular concern was the finding that a quarter of prison-transfer patients were returned to prison by Responsible Medical Officers (RMOs) because they were not engaging with treatment or were deemed too "high risk" to remain detained within the services, circumstances that would be unacceptable when considering discharge via a community care pathway. It is important to further explore the characteristics of people admitted to MSSs from prison, and to investigate how these may differ for individuals who are returned to prison, as compared to those discharged into the community. Aim: (a) To describe the characteristics of prison-transfers who receive an RMO directed discharge from MSSs; and (b) to compare these characteristics by discharge destination; prison return and community discharge. Methods: Prospective cohort comparative study: all prison-transfer patients discharged under the instruction of their RMO over a 6-month period, from 33 NHS medium secure units across England and Wales. Data on patient demographic, clinical and legal characteristics were extracted via full patient health record review and collateral information from clinicians was also obtained. This information was used to complete The Historical, Clinical and Risk--20 items (HCR-20v3) and The Structured Assessment of Protective Factors (SAPROF). Individuals who were returned to prison were compared with those who were discharged to the community. Results: Persons returned to prison represented a vulnerable group at time of discharge as compared to those discharged into the community and had a significantly shorter length of stay in MSSs. Over half of those returned to prison had a length of stay of <6 months. Individuals returned to prison displayed significantly more issues with psychological adjustment at time of discharge, and had a higher risk of future violence and a lower prevalence of protective factors that mitigate subsequent risks of relapse and reoffending. Discussion: MSs in England and Wales are returning vulnerable individuals to prison in lieu of adequate aftercare services. The role of and responsibilities of MSSs as regards admissions from prison needs to be reconsidered.

Interrogating intervention delivery and participants' emotional states to improve engagement and implementation: A realist informed multiple case study evaluation of Engager.

BACKGROUND: 'Engager' is an innovative 'through-the-gate' complex care intervention for male prison-leavers with common mental health problems. In parallel to the randomised-controlled trial of Engager (Trial registration number: ISRCTN11707331), a set of process evaluation analyses were undertaken. This paper reports on the depth multiple case study analysis part of the process evaluation, exploring how a sub-sample of prison-leavers engaged and responded to the intervention offer of one-to-one support during their re-integration into the community. METHODS: To understand intervention delivery and what response it elicited in individuals, we used a realist-informed qualitative multiple 'case' studies approach. We scrutinised how intervention component delivery lead to outcomes by examining underlying causal pathways or 'mechanisms' that promoted or hindered progress towards personal outcomes. 'Cases' (n = 24) were prison-leavers from the intervention arm of the trial. We collected practitioner activity logs and conducted semi-structured interviews with prison-leavers and Engager/other service practitioners. We mapped data for each case against the intervention logic model and then used Bhaskar's (2016) 'DREIC' analytic process to categorise cases according to extent of intervention delivery, outcomes evidenced, and contributing factors behind engagement or disengagement and progress achieved. RESULTS: There were variations in the dose and session focus of the intervention delivery, and how different participants responded. Participants sustaining long-term engagement and sustained change reached a state of 'crises but coping'. We found evidence that several components of the intervention were key to achieving this: trusting relationships, therapeutic work delivered well and over time; and an in-depth shared understanding of needs, concerns, and goals between the practitioner and participants. Those who disengaged were in one of the following states: 'Crises and chaos', 'Resigned acceptance', 'Honeymoon' or 'Wilful withdrawal'. CONCLUSIONS: We demonstrate that the 'implementability' of an intervention can be explained by examining the delivery of core intervention components in relation to the responses elicited in the participants. Core delivery mechanisms often had to be 'triggered' numerous times to produce sustained change. The improvements achieved, sustained, and valued by participants were not always reflected in the quantitative measures recorded in the RCT. The compatibility between the practitioner, participant and setting were continually at risk of being undermined by implementation failure as well as changing external circumstances and participants' own weaknesses. TRIAL REGISTRATION NUMBER: ISRCTN11707331, Wales Research Ethics Committee, Registered 02-04-2016-Retrospectively registered https://doi.org/10.1186/ISRCTN11707331.

Associations of asthma self-management and mental health in adolescents: A scoping review.

BACKGROUND: Adolescent asthma is highly prevalent and frequently uncontrolled despite control being achievable with good self-management. Anxiety, depression, and stress are associated with worse asthma outcomes, and may impact self-management; no previous review has examined this relationship. AIM: This scoping review assessed the nature of the current literature on mental health and asthma self-management among adolescents ages 11 to 24 and synthesized their relationships. METHODS: Guided by the PRISMA-ScR guidelines, we systematically searched the literature using MEDLINE, Embase, CINAHL, PsycInfo, and Scopus in September 2020 and updated it in June 2021. Included studies examined associations between anxiety, depression, and/or stress and asthma self-management in adolescents ages 11-24. We did not restrict study design, location, or date. RESULTS: Out of 1559 records identified, 14 met inclusion criteria. Types of self-management included trigger control, healthcare adherence, and overall symptom prevention and management. Anxiety symptoms were associated with poorer asthma self-management in four studies, but better in three. Depressive symptoms were associated with poorer asthma self-management in five studies, but better in two. Stress was associated with poorer self-management in one study. Mental health symptoms were nearly universally associated with poorer trigger control, but associations with healthcare adherence and overall symptom prevention and management varied. CONCLUSION: Mental health symptoms may facilitate or hinder asthma self-management depending on the types of mental health and self-management. Further research is needed to better understand this relationship and inform future interventions. Providers might assess mental health as a potential barrier to adolescent asthma self-management.

Conducting Randomized Controlled Trials of Complex Interventions in Prisons: A Sisyphean Task?

Randomized Controlled Trials (RCT) are the "gold standard" for measuring the effectiveness of an intervention. However, they have their limitations and are especially complex in prison settings. Several systematic reviews have highlighted some of the issues, including, institutional constraints e.g., "lock-downs," follow-ups, contamination of allocation conditions and a reliance on self-report measures. In this article, we reflect on our experiences and will describe two RCTs. People in prison are a significantly disadvantaged and vulnerable group, ensuring equitable and effective interventions is key to reducing inequality and promoting positive outcomes. We ask are RCTs of complex interventions in prisons a sisyphean task? We certainly don't think so, but we propose that current accepted practice and research designs may be limiting our understanding and ability to test complex interventions in the real-world context of prisons. RCTs will always have their place, but designs need to be flexible and adaptive, with the development of other rigorous methods for evaluating impact of interventions e.g., non-randomized studies, including pre-post implementation studies. With robust research we can deliver quality evidence-based healthcare in prisons - after all the degree of civilization in a society is revealed by entering its prisons.

Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.

The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.

Mitigating SARS-CoV-2 Transmission in Hispanic and Latino Communities-Prince William Health District, Virginia, June 2020.

OBJECTIVES: To identify factors contributing to disproportionate rates of COVID-19 among Hispanic or Latino persons in Prince William Health District, Virginia, and to identify measures to better engage Hispanic and Latino communities in COVID-19 mitigation. METHODS: Data collection proceeded via three methods in June 2020: a quantitative survey of Hispanic or Latino residents, key informant interviews with local leaders familiar with this population, and focus group discussions with Hispanic or Latino community members. RESULTS: Those who worked outside the home, lived in larger households, or lived with someone who had tested positive were more likely to report testing positive for SARS-CoV-2 (unadjusted odds ratios of 2.5, 1.2, and 12.9, respectively). Difficulty implementing COVID-19 prevention practices (reported by 46% of survey respondents), immigration-related fears (repeatedly identified in qualitative data), and limited awareness of local COVID-19 resources (57% of survey respondents spoke little or no English) were identified. Survey respondents also reported declines in their food security (25%) and mental health (25%). CONCLUSIONS: Specific attention to the needs of Hispanic or Latino communities could help reduce the burden of COVID-19. The investigation methods can also be used by other jurisdictions to evaluate the needs of and services provided to diverse underserved populations.

Managing children's forearm fractures in the emergency department.

Forearm fractures are the most common fractures among children and young people aged up to 19 years and these patients frequently present to the emergency department (ED). Many of these fractures can be treated in the ED without the need for inpatient admission. This article examines the assessment, diagnosis and management of forearm fractures. The authors also use a case study format to demonstrate best practice in the treatment of forearm fractures in this age group. The information in this article will enable ED nurses to enhance the experience of children and their families who present with forearm fractures.

Associations among anxiety, self-efficacy, and self-care in rural adolescents with poorly controlled asthma.

BACKGROUND: Rural adolescents are vulnerable to asthma; good self-care can reduce morbidity. The subtypes of anxiety (eg, asthma-related, generalized) may have differential associations with asthma self-care. Low self-efficacy, a determinant of behavior, is associated with increased anxiety. Little is known regarding these relationships in rural adolescents. OBJECTIVE: To evaluate whether anxiety symptoms are associated with asthma symptom prevention and management among rural adolescents and whether self-efficacy mediates these relationships. METHODS: We used baseline data from 197 rural adolescents (mean age = 16 years; 69% girls; 62% Black) who were part of a trial that tested the effectiveness of a school-based asthma intervention. Adolescents completed the Youth Asthma-Related Anxiety Scale, Screen for Child Anxiety and Emotional Disorders, Asthma Management Self-efficacy Index, and Asthma Prevention and Management Indices. Linear regression was performed to test whether: (1) asthma-related and generalized anxiety had curvilinear relationships with self-care; (2) social and separation anxiety had linear relationships with self-care; and (3) self-efficacy mediated relationships. RESULTS: Asthma-related anxiety had a significant curvilinear relationship with prevention (P = 0.001) and a linear association with management (P = .01). Generalized anxiety had a significant curvilinear association with management (P = .03), whereas social anxiety had a significant linear relationship with prevention (P = .04). Self-efficacy partially or fully mediated these relationships. CONCLUSION: Anxiety symptoms were associated with asthma self-care among this sample of rural adolescents, with differing roles for prevention and management. Self-efficacy may be a mechanism to improve asthma self-care among rural adolescents with anxiety. With a lack of self-efficacy, asthma-related, generalized, or social anxiety may motivate adolescents to take steps to care for their asthma.

Managing returns to prison from medium-secure services: qualitative study.

BACKGROUND: Little is known about factors that influence discharge decision-making for people admitted to medium-secure services from prison, particularly for those who are returned to prison following treatment. AIMS: To explore the organisational influences on care pathways through medium-secure services for those admitted from prison. METHOD: We recruited 24 clinicians via purposive and snowball sampling; 13 shared their experiences via a focus group, and 11 shared their experiences via individual semi-structured interviews. A thematic analysis was conducted, producing three overarching themes: maintenance of throughput and service provision, class of two systems, and desirable and undesirable patients. RESULTS: Data indicated external factors that direct and, at times, limit clinicians' pathway decisions, including commissioning criteria and legal status under the Mental Health Act 1983 and within the criminal courts system (i.e. whether on remand or sentenced). These factors also influence how clinicians view the role and function of medium-secure services within the wider forensic mental health system, and therefore the types of patients that are deemed 'appropriate' for continued treatment when making discretionary pathway decisions. CONCLUSIONS: There remains a deficit in adequate resources to meet the mental health needs of prisoners who are admitted to medium-secure services. To meet the clinical need of all admissions, criteria for prolonged treatment in medium-secure services needs to be reconsidered, and it is likely that provision for the medium-secure hospital estate will need to increase substantially if effective rehabilitation of those who transfer from prison is to take place.