Opioid dependence is associated with adverse physical health, mental health and social consequences. Daily oral opiate substitutes offer some treatment gains but several negative associations including daily dosage fluctuations, long-term reliance on services and negative impact on ability to work.

Long-acting injectable buprenorphine (LAIB) is a new treatment option, extensively used in Wales since 2020. We have shown the many gains, including increased treatment retention, reduced service reliance, improved patient satisfaction and increased capacity for people to move on in their recoveries, are likely to be due to LAIBs unique combination of allostatic μ-opioid receptor agonism (craving reduction) and sustained κ-receptor antagonism (anxiolysis). However, ~50% experience resurfacing of mental health and/or trauma symptoms on LAIB that impedes recovery. The Buvidal Psychological Support Service, commissioned by Welsh Government, seeks to develop the evidence base for provision of rapidly accessible, tiered psychological support alongside LAIB to address this. Here we present initial 9-month findings.

Tier 1 of the service offers 8 weekly individual therapy sessions, delivered flexibly over 2–6 months, with an experienced trained therapist focused on psychoeducation, co-production of a trauma and compassioned based formulation, and the development of skills to manage current mental health or trauma symptoms.

Pre- and post-evaluation programme assessed efficacy including: EQ5D-5L, Work and Social Adjustment Scale (WSAS), Clinical Global Impressions (CGI), PRO Severity and Clinical Outcomes in Routine Evaluation –10 (CORE-10).

The service launched in March 2023 with 100 referrals in the first 9 months.

35 patients have completed Tier 1, taking between 2 and 6 months to complete.

Patients who completed Tier 1 showed clinically significant reductions in psychological distress and improvements in global functioning, quality of life and perceived mental health difficulties.

These were statistically significant at p < 0.001 for all measures (EQ5D, ICECAPS, WSAS, CGI, PRO, CORE-10) (28< = n <=34).

Rates of retention in treatment are greater than expected amongst this complex client group and the significant global improvements support the notion that those on LAIB present with increased stability and ability to engage in therapy, and that a tiered flexible approach to therapy can promote psychological safety and engagement and sustained recovery.

We propose that a tiered trauma-focused psychology service is well placed to meet the needs of people on LAIB and should be a core component of LAIB treatment in the UK.

The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of NHSScotland. Assessment of end-of-life (EoL), orphan, and ultra-orphan medicines includes a process to gather evidence from patients and carers during Patient and Clinician Engagement (PACE) meetings. The output of PACE meetings is a consensus statement describing the medicine’s added value from the perspective of patients/carers and clinicians. The PACE statement is used by SMC committee members in decision making. This study compared how PACE participants and SMC committee members rate the importance of information in PACE statements for these medicines.

A survey was undertaken of patient group (PG) representatives and clinicians who participated in PACE meetings, and SMC committee members.

PACE participants who responded (26 PG representatives and 14 clinicians) rated health benefits and ability to take part in normal life as important/very important. Convenience of administration and treatment choice received the lowest rating. Hope for the future received the most diverse response. PACE participants generally rated the importance of quality of life themes higher than committee members (n = 20) but the rank order was similar. Differences between the proportion of PACE participants and committee members who rated themes as important/very important were greatest for treatment choice and hope for the future.

In general, PACE themes and subthemes that were rated highly by PACE participants were also considered important by SMC committee members, indicating that information captured during PACE meetings is relevant when making decisions on EoL, orphan, and ultra-orphan medicines.

Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of NHSScotland. Evidence from patients and carers on end-of-life and orphan medicines is gathered during Patient and Clinician Engagement (PACE) meetings. The output is a consensus statement describing a medicine's added value from the perspective of patients/carers and clinicians, which is used by SMC committee members in decision-making. This study compared the importance of factors in the PACE statement to PACE participants and committee members.

A survey of ninety-eight PACE participants (consisting of forty-two patient group (PG) representatives and fifty-six clinicians) investigated the importance of quality of life (QoL) themes (family/carer impact, health benefits, tolerability, psychological benefit, hope, normal life, treatment choice and convenience) identified from an earlier thematic analysis of PACE statements. The findings from PG representatives and clinicians were compared, and the overall results were further compared with those from a previous survey of committee members (n = 26).

Among PACE participants who responded (twenty-six PG representatives and fourteen clinicians), 100 percent rated ‘health benefits’ and ‘ability to take part in normal life’ as important / very important. ‘Convenience of administration’ and ‘treatment choice’ received the lowest rating with fifteen percent and nineteen percent respectively of PG representatives versus seven percent of clinicians rating each as very important. ‘Hope for the future’ received the most diverse response with fifty-eight percent of PG representatives and fourteen of clinicians rating this as very important.

In general, PACE participants rated importance of QoL themes higher than committee members (n = 21) but the rank order was similar. Differences between the proportion of PACE participants and committee members who rated themes important/very important was greatest for ‘treatment choice’ (sixty-seven percent versus twenty percent respectively) and ‘hope for the future’ (eighty-two percent versus fifty-three percent).

The findings demonstrate some alignment between PACE participants’ and committee members’ responses, supporting the value of the PACE output in decision-making. Areas for further research are highlighted.

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans.

We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites.

Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention.

In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.

Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting.

Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery.

Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria).

We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients’ needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.

Psychotic experiences may emerge in more severe cases of common mental disorders (CMD). Previous work identified that 30% of patients treated by mental health services in primary healthcare, specifically the Improving Access to Psychological Therapies (IAPT) programme in England, reported psychotic experiences, began treatment with more severe CMD and were less likely to reach recovery.

To replicate our previous assessment of psychotic experiences in the IAPT programme using a more sensitive threshold and determine its impact on the prevalence of psychotic experience and likelihood of recovery. Additionally, to compare recovery rates between patients with and without psychotic experiences at the end of therapy.

The Community Assessment of Psychic Experiences (CAPE-P15) with a cut-off of 1.30 was used to determine the prevalence of psychotic experiences. Recovery rates were determined using measures collected in the IAPT programme for depression (PHQ-9) and anxiety (GAD-7). Multi-group growth models estimated improvement trajectories.

In total, 2042 patients with CMD completed the CAPE-P15. The mean age was 39.8. The prevalence of psychotic experiences was 18% higher when using a lower threshold. The recovery rate for patients with psychotic experiences was lower (36%) than for those without (64%). Despite sharing similar improvement trajectories, the higher initial severity of CMD among patients with psychotic experiences impeded likelihood of recovery.

As psychotic experiences may be a marker of severity in CMD, the benefits of identifying these in IAPT populations may also apply to patients with milder experiences. Further investigation of the consequential demands on service provision and how this would affect clinical practice is recommended.

Alexithymia (difficulties in identifying and describing emotion) is a transdiagnostic trait implicated in social–emotional and mental health problems in the general population. Many autistic individuals experience significant social-communication difficulties and elevated anxiety/depression and alexithymia. Nevertheless, the role of alexithymia in explaining individual variability in the quality/severity of social-communication difficulties and/or anxiety and depression symptoms in autism remains poorly understood.

In total, 337 adolescents and adults (autism N = 179) were assessed for alexithymia on the Toronto Alexithymia Scale and for social-communication difficulties, anxiety and depression symptoms. A total of 135 individuals (autism N = 76) were followed up 12–24 months later. We used regression models to establish cross-sectional and longitudinal associations between alexithymia, social-communication difficulties, anxiety and depression symptoms.

Autistic individuals reported significantly higher alexithymia than comparison individuals (p < 0.001, r effect size = 0.48), with 47.3% of autistic females and 21.0% of autistic males meeting cut-off for clinically relevant alexithymia (score ⩾61). Difficulties in describing feelings were particularly associated with current self-reported social-communication difficulties [p < 0.001, β = 0.57, 95% confidence interval (CI) 0.44–0.67] and predicted later social-communication difficulties (p = 0.02, β = 0.43, 95% CI 0.07–0.82). Difficulties in identifying feelings were particularly associated with current anxiety symptom severity (p < 0.001, β = 0.54, 95% CI 0.41–0.77) and predicted later anxiety (p = 0.01; β = 0.31, 95% CI 0.08–0.62).

Our findings suggest that difficulties in identifying v. describing emotion are associated with differential clinical outcomes in autism. Psychological therapies targeting emotional awareness may improve social-communication and anxiety symptoms in autism, potentially conferring long-term benefits.

The Scottish Medicines Consortium (SMC) advises NHS Scotland on the clinical and cost-effectiveness of new medicines. Since 2014, evidence from patients and carers on end-of-life and orphan medicines has been gathered during Patient and Clinician Engagement (PACE) meetings. The output is a consensus statement which describes the added value of a new medicine from the perspective of the patient/carer and clinician. This study investigates the importance of factors identified through PACE to committee members and how these are used in their decision-making.

Survey methodology was used to gain an understanding of the factors from the PACE statement that are most likely to influence members (n = 26) in decision-making. The survey instrument was informed by a literature review and observation of PACE and SMC meetings. Likert scale questions were used to determine the relative importance of factors in the PACE statement, including information relating to eight prominent ‘quality of life’ themes (family/carer impact, health benefits, tolerability, psychological benefit, hope, normal life, treatment choice and convenience), that were identified by an earlier thematic analysis of these statements.

Analysis of survey responses will use mainly descriptive techniques to generate percentages and ranges. Correlation analysis will be considered to investigate relationships between members’ demographics, type of medicine (end-of-life, orphan) and the importance of different factors in the PACE statement. Preliminary results indicate that key quality of life themes highly valued by patients/carers are also important to committee members in their decision making. Challenges in assimilating qualitative patient-based evidence from PACE alongside quantitative clinical and economic data were highlighted.

Findings from this survey will provide valuable insight into how PACE evidence is used by SMC decision makers alongside traditional clinical and economic evidence and will help shape future improvements to the PACE methodology.

Medicines regulation has become increasingly adaptive to support earlier patient access but the immature clinical data is often challenging for health technology assessment decision-makers due to high levels of uncertainty on long term risks and benefits. Scottish Medicines Consortium (SMC) is therefore exploring new, more adaptive approaches to help manage this challenge.

SMC consulted with key stakeholders including clinicians, the pharmaceutical industry and patient groups on a number of options that would allow the committee to make an interim decision that would be revisited based on later evidence. The ability to collect robust patient level data given data capabilities in National Health Service Scotland (NHSScotland) was an important consideration.

To ensure that additional evidence would be available to inform a re-assessment, the new approach applies to medicines with a Conditional Marketing Authorisation (MA) from the European Medicines Agency (EMA). This obligates the company to provide specified clinical data to the regulator within a pre-set timeframe. For these medicines, the SMC decision-making committee can accept or not recommend the medicine as at present but can also accept the medicine on an interim basis, if the regulator's mandated Specific Obligations are likely to address the uncertainties in the clinical evidence. When the regulator converts the MA from conditional to standard, the company is required to make a further SMC submission to allow a reassessment and a final decision. The company can also provide additional supplementary post-licensing patient level evidence at reassessment.

This new decision option allows SMC to test an approach to managing uncertainty targeted at a small number of promising new medicines where there is unmet patient need, with the reassurance that a final decision will be supported by additional clinical data.

Medicines for very rare conditions present challenges for healthcare globally due to uncertain evidence and often extremely high costs. In 2014, SMC introduced an ultra-orphan framework placing less emphasis on the cost per quality adjusted life year (QALY). Despite this, many medicines continued to be not recommended. A new pathway aimed at improved patient access based on further evidence collection is now being implemented.

The development of the new pathway has involved collaboration with key stakeholders including patient groups, the pharmaceutical industry, and clinicians. Medicines that meet a new definition (based on four criteria including the prevalence of the condition treated) will be appraised by the SMC committee and a data collection plan will then be agreed with the pharmaceutical company.

From April 2019, medicines validated as ultra-orphans will initially be appraised using the broader decision-making framework and the SMC committee will outline key uncertainties in the clinical effectiveness. The medicine will then be available for a period of at least three years while further data are gathered, potentially comprising ongoing clinical trials, registry data, and patient reported outcome measures. SMC will then re-assess the clinical and economic evidence to inform a final decision on routine use of the medicine in NHS Scotland.

The new pathway for ultra-orphan medicines will allow further evidence on their longer-term clinical benefits to be collected before a final decision on routine use. This approach reflects the current direction of travel in medicines regulation, by making medicines that address an unmet need available to patients at an earlier stage of development.

Schizophrenia is associated with impaired neurodevelopment as indexed by lower premorbid IQ. We examined associations between erythrocyte sedimentation rate (ESR), a marker of low-grade systemic inflammation, IQ, and subsequent schizophrenia and other non-affective psychoses (ONAP) to elucidate the role of neurodevelopment and inflammation in the pathogenesis of psychosis.

Population-based data on ESR and IQ from 638 213 Swedish men assessed during military conscription between 1969 and 1983 were linked to National Hospital Discharge Register for hospitalisation with schizophrenia and ONAP. The associations of ESR with IQ (cross-sectional) and psychoses (longitudinal) were investigated using linear and Cox-regression. The co-relative analysis was used to examine effects of shared familial confounding. We examined mediation and moderation of effect between ESR and IQ on psychosis risk.

Baseline IQ was associated with subsequent risk of schizophrenia (adjusted HR per 1-point increase in IQ = 0.961; 95% confidence interval (CI) 0.960–0.963) and ONAP (adjusted HR = 0.973; 95% CI 0.971–0.975). Higher ESR was associated with lower IQ in a dose-response fashion. High ESR was associated with increased risk for schizophrenia (adjusted HR = 1.14; 95% CI 1.01–1.28) and decreased risk for ONAP (adjusted HR = 0.85; 95% CI 0.74–0.96), although these effects were specific to one ESR band (7–10 mm/hr). Familial confounding explained ESR-IQ but not ESR-psychoses associations. IQ partly mediated the ESR-psychosis relationships.

Lower IQ is associated with low-grade systemic inflammation and with an increased risk of schizophrenia and ONAP in adulthood. Low-grade inflammation may influence schizophrenia risk by affecting neurodevelopment. Future studies should explore the differential effects of inflammation on different types of psychosis.

New approaches are needed to safely reduce emergency admissions to hospital by targeting interventions effectively in primary care. A predictive risk stratification tool (PRISM) identifies each registered patient's risk of an emergency admission in the following year, allowing practitioners to identify and manage those at higher risk. We evaluated the introduction of PRISM in primary care in one area of the United Kingdom, assessing its impact on emergency admissions and other service use.

We conducted a randomized stepped wedge trial with cluster-defined control and intervention phases, and participant-level anonymized linked outcomes. PRISM was implemented in eleven primary care practice clusters (total thirty-two practices) over a year from March 2013. We analyzed routine linked data outcomes for 18 months.

We included outcomes for 230,099 registered patients, assigned to ranked risk groups.

Overall, the rate of emergency admissions was higher in the intervention phase than in the control phase: adjusted difference in number of emergency admissions per participant per year at risk, delta = .011 (95 percent Confidence Interval, CI .010, .013). Patients in the intervention phase spent more days in hospital per year: adjusted delta = .029 (95 percent CI .026, .031). Both effects were consistent across risk groups.

Primary care activity increased in the intervention phase overall delta = .011 (95 percent CI .007, .014), except for the two highest risk groups which showed a decrease in the number of days with recorded activity.

Introduction of a predictive risk model in primary care was associated with increased emergency episodes across the general practice population and at each risk level, in contrast to the intended purpose of the model. Future evaluation work could assess the impact of targeting of different services to patients across different levels of risk, rather than the current policy focus on those at highest risk.

Emergency admissions to hospital are a major financial burden on health services. In one area of the United Kingdom (UK), we evaluated a predictive risk stratification tool (PRISM) designed to support primary care practitioners to identify and manage patients at high risk of admission. We assessed the costs of implementing PRISM and its impact on health services costs. At the same time as the study, but independent of it, an incentive payment (‘QOF’) was introduced to encourage primary care practitioners to identify high risk patients and manage their care.

We conducted a randomized stepped wedge trial in thirty-two practices, with cluster-defined control and intervention phases, and participant-level anonymized linked outcomes. We analysed routine linked data on patient outcomes for 18 months (February 2013 – September 2014). We assigned standard unit costs in pound sterling to the resources utilized by each patient. Cost differences between the two study phases were used in conjunction with differences in the primary outcome (emergency admissions) to undertake a cost-effectiveness analysis.

We included outcomes for 230,099 registered patients. We estimated a PRISM implementation cost of GBP0.12 per patient per year.

Costs of emergency department attendances, outpatient visits, emergency and elective admissions to hospital, and general practice activity were higher per patient per year in the intervention phase than control phase (adjusted δ = GBP76, 95 percent Confidence Interval, CI GBP46, GBP106), an effect that was consistent and generally increased with risk level.

Despite low reported use of PRISM, it was associated with increased healthcare expenditure. This effect was unexpected and in the opposite direction to that intended. We cannot disentangle the effects of introducing the PRISM tool from those of imposing the QOF targets; however, since across the UK predictive risk stratification tools for emergency admissions have been introduced alongside incentives to focus on patients at risk, we believe that our findings are generalizable.

A predictive risk stratification tool (PRISM) to estimate a patient's risk of an emergency hospital admission in the following year was trialled in general practice in an area of the United Kingdom. PRISM's introduction coincided with a new incentive payment (‘QOF’) in the regional contract for family doctors to identify and manage the care of people at high risk of emergency hospital admission.

Alongside the trial, we carried out a complementary qualitative study of processes of change associated with PRISM's implementation. We aimed to describe how PRISM was understood, communicated, adopted, and used by practitioners, managers, local commissioners and policy makers. We gathered data through focus groups, interviews and questionnaires at three time points (baseline, mid-trial and end-trial). We analyzed data thematically, informed by Normalisation Process Theory (1).

All groups showed high awareness of PRISM, but raised concerns about whether it could identify patients not yet known, and about whether there were sufficient community-based services to respond to care needs identified. All practices reported using PRISM to fulfil their QOF targets, but after the QOF reporting period ended, only two practices continued to use it. Family doctors said PRISM changed their awareness of patients and focused them on targeting the highest-risk patients, though they were uncertain about the potential for positive impact on this group.

Though external factors supported its uptake in the short term, with a focus on the highest risk patients, PRISM did not become a sustained part of normal practice for primary care practitioners.