A Realist Review of How Community-Based Drug Checking Services Could Be Designed and Implemented to Promote Engagement of People Who Use Drugs

With rising numbers of drug-related deaths in the UK and globally, exploration of interventions that seek to reduce drug-related harm is essential. Drug checking services (DCS) allow people to submit drug samples for chemical analysis and receive feedback about the sample, as well as harm reduction advice. The use of DCS is often linked to festival and/or nightlife settings and to so-called ‘recreational’ drug use, but research has also shown the potential of community-based DCS as an intervention serving more varied demographics of people who use drugs, including more marginalised individuals and those experiencing drug dependence. Whilst there is a growing evidence base on the effectiveness of drug checking as a harm reduction intervention, there is still limited evidence of the underlying mechanisms and processes within DCS which may aid implementation and subsequent engagement of people who use drugs. This presents a challenge to understanding why engagement differs across types of DCS, and how best to develop and deliver services across different contexts and for different populations. To explore the contexts and mechanisms which impact engagement in community-based DCS, a realist review was undertaken to synthesise the international evidence for the delivery and implementation of DCS. There were 133 sources included in the review. From these sources the underlying contexts, mechanisms, and outcomes relating to DCS implementation and engagement were developed and refined into seven programme theories. The findings of this review are theoretically novel and hold practical relevance for the design of DCS, with implications for optimisation, tailoring, and implementing services to reach individuals in different settings

Evaluation of a domestic violence intervention in the maternity and sexual health services of a UK hospital.

This paper reports on an evaluation of a domestic violence intervention in the maternity and sexual health services of a UK hospital. The intervention encompassed guidelines, staff training, inclusion of routine enquiry for domestic violence with all patients, and referral of women disclosing violence to an on-site advocacy service. An "assumption querying" approach was applied to evaluate the intervention. Programmatic assumptions were identified and tested using interviews with service providers and patients, review of patient records, and pre- and post-training questionnaires. Domestic violence training resulted in changes in health professionals' knowledge and practice in the short-term, but universal routine enquiry was not achieved even in a context of organisational support, guidelines, training and advocacy. Potential and actual harm occurred, including breaches of confidentiality and failure to document evidence, limiting women's ability to access civil and legal remedies. Advocacy support led to positive outcomes for many women, as long as support to maintain positive changes, whether women stayed with or left the violent partner, continued to be given. Maternity and sexual health services were found to be opportune points of intervention for domestic violence services that combine routine enquiry by clinicians, support after disclosure and attention to harm reduction

Controversies in orthopaedic oncology

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR