A multicomponent psychosocial intervention to reduce substance use by adolescents involved in the criminal justice system: the RISKIT-CJS RCT.

Background: Substance use and offending are related in the context of other disinhibitory behaviours. Adolescents involved in the criminal justice system constitute a particularly vulnerable group, with a propensity to engage in risky behaviour that has long-term impact on their future health and well-being. Previous research of the RISKIT programme provided evidence of a potential effect in reducing substance use and risky behaviour in adolescents. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of a multicomponent psychosocial intervention compared with treatment as usual in reducing substance use for substance-using adolescents involved in the criminal justice system. Design: A mixed-methods, prospective, pragmatic, two-arm, randomised controlled trial with follow-up at 6 and 12 months post randomisation. Setting: The study was conducted across youth offending teams, pupil referral units and substance misuse teams across four areas of England (i.e. South East, London, North West, North East). Participants: Adolescents aged between 13 and 17 years (inclusive), recruited between September 2017 and June 2020. Interventions: Participants were randomised to treatment as usual or to treatment as usual in addition to the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme was a multicomponent intervention and consisted of two individual motivational interviews with a trained youth worker (lasting 45 minutes each) and two group sessions delivered over half a day on consecutive weeks. Main outcome measures: At 12 months, we assessed per cent days abstinent from substance use over the previous 28 days. Secondary outcome measures included well-being, motivational state, situational confidence, quality of life, resource use and fidelity of interventions delivered. Results: A total of 693 adolescents were assessed for eligibility, of whom 505 (73%) consented. Of these, 246 (49%) were allocated to the RISKIT-CJS intervention and 259 (51%) were allocated to treatment as usual only. At month 12, the overall follow-up rate was 57%: 55% in the RISKIT-CJS arm and 59% in the treatment-as-usual arm. At month 12, we observed an increase in per cent days abstinent from substances in both arms of the study, from 61% to 85%, but there was no evidence that the RISKIT-CJS intervention was superior to treatment as usual. A similar pattern was observed for secondary outcomes. The RISKIT-CJS intervention was not found to be any more cost-effective than treatment as usual. The qualitative research indicated that young people were positive about learning new skills and acquiring new knowledge. Although stakeholders considered the intervention worthwhile, they expressed concern that it came too late for the target population. Limitations: Our original aim to collect data on offences was thwarted by the onset of the COVID-19 pandemic, and this affected both the statistical and economic analyses. Although 214 (87%) of the 246 participants allocated to the RISKIT-CJS intervention attended at least one individual face-to-face session, 98 (40%) attended a group session and only 47 (19%) attended all elements of the intervention. Conclusions: The RISKIT-CJS intervention was no more clinically effective or cost-effective than treatment as usual in reducing substance use among adolescents involved in the criminal justice system. Future research: The RISKIT-CJS intervention was considered more acceptable, and adherence was higher, in pupil referral units and substance misuse teams than in youth offending teams. Stakeholders in youth offending teams thought that the intervention was too late in the trajectory for their population. Trial registration: This trial is registered as ISRCTN77037777. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

We explored how useful a psychological intervention was in reducing substance use among young people who had some involvement in the criminal justice system. We recruited young people aged between 13 and 17 years in four areas of England (i.e. South East, London, North West and North East). Young people were recruited from youth offending teams, pupil referral units and substance misuse teams. Those young people who were willing to participate were offered usual treatment and half, chosen at random, were offered an opportunity to take part in the RISKIT-Criminal Justice System (RISKIT-CJS) programme. The RISKIT-CJS programme had four distinct parts. The first was a 1-hour session that used an approach called motivational interviewing to explore the young person's substance use and discuss different strategies to change their behaviour. This was followed by two group sessions delivered over 2 consecutive weeks. These group sessions addressed risks associated with substance use, what triggers use and the health and social consequences. In addition, young people were taught new skills to help them manage in situations in which they might normally use substances. At the end of the group sessions, the young people had another motivational interview. Twelve months after participants started, we found that the frequency of substance use had decreased in both groups; however, the RISKIT-CJS intervention was no better than treatment as usual. When we spoke with young people who had taken part and staff involved with this population, we got a mixed picture. In some settings, particularly pupil referral units, the RISKIT-CJS intervention was well received by young people and staff, and staff felt that it was a useful additional resource to the work that they were currently undertaking. On the other hand, in the youth offending teams, the staff thought that the programme was too different from their normal work to be implemented easily and they considered the population they work with too established in their substance use and criminal activity to benefit from the programme.

What are the impacts of setting up new medical schools? A narrative review.

BACKGROUND: The growth of the UK's population together with an aging society with increasingly complex health and social care needs has placed a greater demand on statutory care services. In view of this emerging landscape, the UK Government has sought to increase its medically trained workforce in order to better respond to the demands placed on the health service. Five universities were announced as homes to new medical schools offering undergraduate places to boost the numbers of doctors training in England. The aim of this narrative review was to explore how new medical schools could improve the health outcomes of the local population and evaluate the potential contribution it may make to the local economy, workforce and to research and innovation. METHODS: A narrative review was undertaken using a systematic approach for the search literature strategy. The articles were evaluated by undertaking a critical assessment evaluating the fitness of a paper for review according to results, methods used to test the hypothesis, conclusions and impact and limitations. Thematic analysis was employed to organise and summarise the findings across a heterogeneous body of literature included in the review. The analysis was developed in an inductive manner and there were not any predefined themes to guide data extraction and analysis. RESULTS: Thirty-six articles were selected for inclusion for this narrative review. The review identified six key themes: influence of prior rural exposure, medical school environment and rural enrichment programmes, workforce, health outcomes of local populations, social accountability, economic contribution of medical schools to communities and impact on rural research. CONCLUSIONS: The studies included found a wealth of information on a wide-range of topics on the expansion of undergraduate education and its implications on the future medical workforce. It was shown that medical schools can have a positive effect on the health, social, economic and research activity of a region, but this literature tended to be heterogeneous in focus without consideration of the inter-connections between the wider societal and economic impacts arising from long-term sustainable change being brought to a region.

Incorporating the interaction between health and work into the undergraduate medical curriculum - a qualitative evaluation of a teaching pilot in English medical schools.

Introduction: There is a growing recognition of the impact of work on health both positive and negative. It is important that all health care professionals are equipped to understand the effects of work and worklessness on health and help patients remain in work or manage a healthy return to work where appropriate. Despite explicit reference to health and work in the General Medical Council's Outcomes for Graduates, currently, this is not a theme that is integrated across the undergraduate medical curricula.Aim: This study evaluates medical tutors' and undergraduates' perspectives of a selection of health and work topics in a teaching pilot to consider the suitability and appropriateness for delivery, integration into the curriculum, tailoring of the resources, and appropriateness and expected attainment of learning objectives.Methods: Qualitative, semi-structured interviews and focus groups were carried out with five medical tutors and 36 undergraduates. Interviews and focus groups were recorded, transcribed and thematically analysed.Results: Medical tutors and undergraduates identified suitability of appropriate subject specialities and years of teaching, whether learning objectives were important and if these had been achieved, and recommendations for future delivery.Discussion: Medical tutors were committed to delivering the health and work topics with the flexibility of tailoring the resources to existing subject specialities and with respect to the year of study. Learning objectives were perceived appropriate by tutors, despite ambivalence about their importance from some undergraduates. Resources were identified as having relevance to public health undergraduate teaching and during general practice placements.

The role of the Quality and Outcomes Framework in the care of long-term conditions: a systematic review.

BACKGROUND: Improving care for people with long-term conditions is central to NHS policy. It has been suggested that the Quality and Outcomes Framework (QOF), a primary care pay-for-performance scheme that rewards practices for delivering effective interventions in long-term conditions, does not encourage high-quality care for this group of patients. AIM: To examine the evidence that the QOF has improved quality of care for patients with long-term conditions. DESIGN AND SETTING: This was a systematic review of research on the effectiveness of the QOF in the UK. METHOD: The authors searched electronic databases for peer-reviewed empirical quantitative research studying the effect of the QOF on a broad range of processes and outcomes of care, including coordination and integration of care, holistic and personalised care, self-care, patient experience, physiological and biochemical outcomes, health service utilisation, and mortality. Because the studies were heterogeneous, a narrative synthesis was carried out. RESULTS: The authors identified three systematic reviews and five primary research studies that met the inclusion criteria. The QOF was associated with a modest slowing of both the increase in emergency admissions and the increase in consultations in severe mental illness (SMI), and modest improvements in diabetes care. The nature of the evidence means that the authors cannot be sure that any of these associations is causal. No clear effect on mortality was found. The authors found no evidence that the QOF influences integration or coordination of care, holistic care, self-care, or patient experience. CONCLUSION: The NHS should consider more broadly what constitutes high-quality primary care for people with long-term conditions, and consider other ways of motivating primary care to deliver it.

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B4 (LTB4) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB4, a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots.

Pragmatic randomised controlled trial to evaluate the effectiveness and cost effectiveness of a multi-component intervention to reduce substance use and risk-taking behaviour in adolescents involved in the criminal justice system: A trial protocol (RISKIT-CJS).

BACKGROUND: Adolescence is a critical developmental stage when young people make lifestyle choices that have the potential to impact on their current and future health and social wellbeing. The relationship between substance use and criminal activity is complex but there is clear evidence that the prevalence of problematic substance use is far higher among adolescent offenders than the general adolescent population. Adolescent offenders are a marginalized and vulnerable population who are significantly more likely to experience health and social inequalities in later life than their non-offending peers. There is a paucity of evidence on effective interventions to address substance use and risk-taking behaviours in adolescent offender populations but it is clear that preventative or abstinence orientated interventions are not effective. RISKIT-CJS is an intervention developed in collaboration with young people taking account of the current best evidence. Feasibility and pilot studies have found the intervention addresses the needs of adolescents, is acceptable and has demonstrated potential in reducing substance use and risk-taking behavior. METHODS: The study is a mixed method, two-armed, prospective, pragmatic randomized controlled trial with individual randomisation to either treatment as usual alone or the RISKIT-CJS intervention in addition to treatment as usual. Adolescents, aged 13 to 17 years inclusive, engaged with the criminal justice system who are identified as having problematic substance use are eligible to participate. The study will be conducted across three geographical areas; South and South East England, London and North East England between March 2017 and February 2019. DISCUSSION: The study represents an ambitious programme of work to address an area of need for a marginalized and vulnerable population. TRIAL REGISTRATION: ISRCTN77037777 registered 15/09/2016.

Addressing the crisis of GP recruitment and retention: a systematic review.

BACKGROUND: The numbers of GPs and training places in general practice are declining, and retaining GPs in their practices is an increasing problem. AIM: To identify evidence on different approaches to retention and recruitment of GPs, such as intrinsic versus extrinsic motivational determinants. DESIGN AND SETTING: Synthesis of qualitative and quantitative research using seven electronic databases from 1990 onwards (Medline, Embase, Cochrane Library, Health Management Information Consortium [HMIC], Cumulative Index to Nursing and Allied Health Literature (Cinahl), PsycINFO, and the Turning Research Into Practice [TRIP] database). METHOD: A qualitative approach to reviewing the literature on recruitment and retention of GPs was used. The studies included were English-language studies from Organisation for Economic Cooperation and Development countries. The titles and abstracts of 138 articles were reviewed and analysed by the research team. RESULTS: Some of the most important determinants to increase recruitment in primary care were early exposure to primary care practice, the fit between skills and attributes, and a significant experience in a primary care setting. Factors that seemed to influence retention were subspecialisation and portfolio careers, and job satisfaction. The most important determinants of recruitment and retention were intrinsic and idiosyncratic factors, such as recognition, rather than extrinsic factors, such as income. CONCLUSION: Although the published evidence relating to GP recruitment and retention is limited, and most focused on attracting GPs to rural areas, the authors found that there are clear overlaps between strategies to increase recruitment and retention. Indeed, the most influential factors are idiosyncratic and intrinsic to the individuals.

Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled controls, chitosan implants solidified with thrombin elicited a more hyaline and structurally integrated osteochondral unit, features needed for long-term durability.

[Use of procalcitonine in intensive care units: comparison of semi quantitative PCT-Q Brahms assay with automated PCT-Kryptor assay]. / Utilisation au quotidien de la procalcitonine dans un service de soins intensifs : comparaison de la technique semi-quantitative PCT-Q Brahms à celle automatisée PCT-Kryptor.

Procalcitonine (PCT) is recognized as a major and specific biomarker in diagnosis of bacterial infection. Used early in sepsis, it allows immediate administration of antibiotics and monitoring its effectiveness. Confronted on systemic inflammation response syndrom (SIRS), physicians must react quickly and effectively to evaluate bacterial infection and sepsis. The objective of this study was to compare analytical and clinical performances of semi-quantitative PCT-Q assay (Brahms) with quantitative and automated assay such on Kryptor (Brahms). Fifty blood samples of intensive care patients were compared. The analytical performance observed with PCT-Q assay is accurate: linear ratio kappa of 0.912 (95% CI 0.61, 0.97) and a good correlation between these techniques (p < 0.0001) (MedCalc software) were observed. Three discordances were observed and confirm the difficulties of reading for values close to 0.5 ng/mL. For these patients, PCT result showed its interest to discriminate local infection of a sepsis, to stop antibiotherapy with broad spectrum and to consolidate a therapeutic effectiveness in multi-visceral failure context. The semi-quantitative assay seems adapted for a fast and reliable evaluation of PCT in a general-purpose laboratory, not requiring neither dedicated analyzer, nor complex technicality but a control of the visual evaluation of results. It could be used for diagnosis of sepsis without monitoring precisely therapeutic follow-up.

Standardized three-dimensional volumes of interest with adapted surfaces for more precise subchondral bone analyses by micro-computed tomography.

Micro-computed tomography can be used to analyze subchondral bone features below treated cartilage defects in animal models. However, standardized methods for generating precise three-dimensional (3D) volumes of interest (VOI) below curved articular surfaces are lacking. The aims of this study were to develop standardized 3D VOI models adapted to the curved articular surface, and to characterize the subchondral bone specifically below a cartilage defect zone in intact and defect femoral trochlea. Skeletally mature rabbit distal femurs (N = 8 intact; N = 6 with acute debrided and microdrilled trochlear defects) were scanned by micro-computed tomography. Bone below the defect zone (3.5 mm width, 3.6 mm length, 1 mm deep) was quantified using simple geometric rectangular VOIs, and an optimized 3D VOI model with an adapted surface curvature, the Rectangle with Adapted Surface (RAS) model. In addition, a 250-µm-thick Curved-RAS model analyzed bone at three discrete subchondral levels. Simple geometric VOIs failed to analyze ~17% of the tissue volume, mainly near the top of the curved trochlear ridges. The RAS models revealed that after debridement and drilling, only 31% of the original bone remained within the VOI and bone loss was mainly accounted for by surgical debridement. Adapted surface VOIs are better than simple geometric VOI shapes for quantifying structural features of subchondral bone below a curved articular surface. Structural differences between the bone plate and cancellous bone were best captured using the smaller, depth-dependent Curved-RAS model.

Scaffold-guided subchondral bone repair: implication of neutrophils and alternatively activated arginase-1+ macrophages.

BACKGROUND: Microfracture and drilling elicit a cartilage repair whose quality depends on subchondral bone repair. Alternatively activated (AA) macrophages express arginase-1, release angiogenic factors, and could be potential mediators of trabecular bone repair. HYPOTHESIS: Chitosan-glycerol phosphate (GP)/blood implants elicit arginase-1+ macrophages in vivo through neutrophil-dependent mechanisms and improve trabecular bone repair of drilled defects compared with drilling alone. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral trochlear cartilage defects were created in 15 rabbits, microdrilled, and treated or not with chitosan-GP/blood implant to analyze AA macrophages, CD-31+ blood vessels, bone, and cartilage repair after 1, 2, or 8 weeks. Neutrophil and macrophage chemotaxis to rabbit subcutaneous implants of autologous blood and chitosan-GP (+/-blood) was quantified at 1 or 7 days. In vitro, sera from human chitosan-GP/blood and whole blood clots cultured at 37 degrees C were analyzed by proteomics and neutrophil chemotaxis assays. RESULTS: Chitosan-GP/blood clots and whole blood clots released a similar profile of chemotactic factors (PDGF-BB, IL-8/CXCL8, MCP-1/CCL2, and no IL-1beta or IL-6), although chitosan clot sera attracted more neutrophils in vitro. Subcutaneous chitosan-GP (+/-blood) implants attracted more neutrophils (P < .001) and AA macrophages than whole blood clots in vivo. In repairing subchondral drill holes, chitosan-GP/blood implant attracted more AA macrophages at 1 and 2 weeks and more blood vessels at 2 weeks compared with drilled controls. Treatment elicited a more complete woven bone repair at 8 weeks than controls (P = .0011) with a more uniform, integrated collagen type II+ cartilage repair tissue. CONCLUSION AND CLINICAL RELEVANCE: AA macrophages may play a role in the regeneration of subchondral bone, and chitosan-GP can attract and transiently accumulate these cells in the repair tissue. The resulting improved subchondral repair could be advantageous toward enhancing integration of a restored chondral surface to the subchondral bone.

Role of MSK1 in the signaling pathway leading to VEGF-mediated PAF synthesis in endothelial cells.

Vascular endothelial growth factor (VEGF) inflammatory effects require acute platelet-activating factor (PAF) synthesis by endothelial cells (EC). We previously reported that VEGF-mediated PAF synthesis involves the activation of VEGF receptor-2/Neuropilin-1 complex, which is leading to the activation of p38 and p42/44 mitogen-activated protein kinases (MAPKs) and group V secretory phospholipase A(2) (sPLA(2)-V). As the mechanisms regulating sPLA(2)-V remain unknown, we addressed the role of the mitogen- and stress-activated protein kinase-1 (MSK1), which can be rapidly and transiently activated by p38 or p42/44 MAPKs. In native bovine aortic endothelial cells (BAEC), we observed a constitutive protein interaction of MSK1 with p38, p42/44 MAPKs, and sPLA(2)-V. These protein interactions were maintained in BAEC transfected either with the empty vector pCDNA3.1, wild-type MSK1 (MSK1-WT) or N-terminal dead kinase MSK1 mutant (MSK1-D195A). However, in BAEC expressing C-terminal dead kinase MSK1 mutant (MSK1-D565A), the interaction between MSK1 and sPLA(2)-V was reduced by 82% and 90% under basal and VEGF-treated conditions as compared to native BAEC. Treatment with VEGF for 15 min increased basal PAF synthesis in native BAEC, pCDNA3.1, MSK1-WT, and MSK1-D195A by 166%, 139%, 125%, and 82%, respectively. In contrast, PAF synthesis was prevented in cells expressing MSK1-D565A mutant. These results demonstrate the essential role of the C-terminal domain of MSK1 for its constitutive interaction with sPLA(2)-V, which appears essential to support VEGF-mediated PAF synthesis.