Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis

Objective. To identify the number of haemodialysis patients with diabetes in a large NHS Trust, their current glycaemic control, and the impact on other renal specific outcomes. Design. Retrospective, observational, cross-sectional study. Methods. Data was collected from an electronic patient management system. Glycaemic control was assessed from HbA1c results that were then further adjusted for albumin (Alb) and haemoglobin (Hb). Interdialytic weight gains were analysed from weights recorded before and after dialysis, 2 weeks before and after the most recent HbA1c date. Amputations were identified from electronic records. Results. 39% of patients had poor glycaemic control (HbA1c > 8%). Adjusted HbA1c resulted in a greater number of patients with poor control (55%). Significant correlations were found with interdialytic weight gains (P<0.02, r=0.14), predialysis sodium (P<0.0001, r=-1.9), and predialysis bicarbonate (P<0.02, r=0.12). Trends were observed with albumin and C-reactive protein. Patients with diabetes had more amputations (24 versus 2). Conclusion. Large number of diabetic patients on haemdialysis have poor glycaemic control. This may lead to higher interdialytic weight gains, larger sodium and bicarbonate shifts, increased number of amputations, and possibly increased inflammation and decreased nutritional status. Comprehensive guidelines and more accurate long-term tests for glycaemic control are needed

Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis

Objective. To identify the number of haemodialysis patients with diabetes in a large NHS Trust, their current glycaemic control, and the impact on other renal specific outcomes. Design. Retrospective, observational, cross-sectional study. Methods. Data was collected from an electronic patient management system. Glycaemic control was assessed from HbA1c results that were then further adjusted for albumin (Alb) and haemoglobin (Hb). Interdialytic weight gains were analysed from weights recorded before and after dialysis, 2 weeks before and after the most recent HbA1c date. Amputations were identified from electronic records. Results. 39% of patients had poor glycaemic control (HbA1c &gt; 8%). Adjusted HbA1c resulted in a greater number of patients with poor control (55%). Significant correlations were found with interdialytic weight gains ( &lt; 0.02, = 0.14), predialysis sodium ( &lt; 0.0001, = −1.9), and predialysis bicarbonate ( &lt; 0.02, = 0.12). Trends were observed with albumin and C-reactive protein. Patients with diabetes had more amputations (24 versus 2). Conclusion. Large number of diabetic patients on haemdialysis have poor glycaemic control. This may lead to higher interdialytic weight gains, larger sodium and bicarbonate shifts, increased number of amputations, and possibly increased inflammation and decreased nutritional status. Comprehensive guidelines and more accurate long-term tests for glycaemic control are needed

Patient, Physician, or Observer: Qualitative Analysis of a Peer Role-play for Developing Communication Skills

Learning Objectives: Identify and compare the lessons students learn from participating in peer role-play as either physician, patient, or observer.Background: Communication Skills Training (CST) is an important part of undergraduate medical training, with instructional modalities including peer role-play (RP) and simulated patients (SP). Research comparing effectiveness of RP and SP is mixed, with some evidence suggesting RP may better develop empathy. Unlike with SP CST, students participating in RP CST spend time portraying patients. The impact of this patient role-play has not been explored.Methods: We developed a virtual RP case in which a physician communicates diagnostic uncertainty to a patient being discharged from the emergency department. We scripted three roles: physician, patient, and observer. Third-year medical students complete the RP, then enter small-group break-out rooms (10 students) for facilitated debriefing, which we transcribe. Each session included only students from a single role. Qualitative analysis began with generation of inductive codes. Pairs of researchers developed preliminary codebooks for each role, testing codes against several transcriptions. We integrated these codebooks into a master codebook to be used on all transcriptions.Results: 273 students participated, yielding 24 transcriptions with &gt;85,000 words. Preliminary analysis revealed themes that differed between roles. Students playing the physician tend to emphasize useful lessons they gleaned, whereas those playing patients discussed empathy and the emotional impact of decisions by the physician role.Conclusion: Initial results indicate that role-playing as patient may support learning in ways that playing as physician does not. Educators should utilize RP with an eye towards these benefits, emphasizing engagement when playing the role of the patient

Exploring the cellular uptake and localisation of phosphorescent rhenium fac-tricarbonyl metallosurfactants as a function of lipophilicity

A systematic study of the cellular uptake of emissive complexes as a function of their lipophilicity is presented. Here a series of amphiphilic rhenium fac-tricarbonyl bisimine complexes bearing axial substituted imidazole or thiazole ligands, [Re(bpy)(CO)3(ImCnHm)]+ {n = 1 m = 3 (1+), n = 4 m = 9 (2+), n = 8 m = 17 (3+), n = 12 m = 25 (4+), n = 16 m = 33 (5+), n = 2 m = 3 (6+); bpy = 2,2'-bipyridine, Im = imidazole} and [Re(bpy)(CO)3(L)]+ {L = 1-mesitylimidazole, ImMes (7+), 4,5-dimethylthiazole, dmt (8+) and 4-methyl-5-thiazole-ethanol, mte (9+)} is reported. The X-ray crystal structures of 2+, 8+ and 9+ confirm the geometry and expected distribution of ligands and indicated that the plane of the imidazole/thiazole ring is approximately parallel to the long axis of the bipy ligand. Luminescence studies revealed excellent properties for their use in cell imaging with visible excitation and broad emission profiles. Their uptake in two distinct species has been examined by fluorescence imaging of the diplomonad fish parasite Spironucleus vortens (S. vortens) and rod-shaped yeast Schizosaccharomyces pombe (Schiz. pombe) as a function of their lipophilicity. The uptake of the complexes was highest for the more lipophilic 2+-5+ in both S. vortens and Schiz. pombe in which the long alkyl chain aids in crossing bilipid membranes. However, the increased lipophilicity of longer chains also resulted in greater toxicity. Localisation over the whole cell varied with differing alkyl chain lengths with complex 2+ preferentially locating to the nucleus of S. vortens, 3+ showing enhanced nuclear partitioning in Schiz. pombe, and 4+ for the remaining cell wall bound in the case of S. vortens. Interestingly, complexes of intermediate lipophilicity such as 7+ and 8+ showed reasonable uptake, proved to be non-toxic, and were capable of crossing exterior cell walls and localising in the organelles of the cells.</p

Influencing policy and practice for young people in foster care: Learning from a model of collective participation

A strong rationale for the collective participation of young people in care regarding decisions related to their care experience is evident in literature and statutory reports. However international research demonstrates challenges relating to participation in the childcare system. This includes context specific factors relating to issues in the field of child protection and welfare, along with more universal challenges such as access and diversity of representation, the imposition of adult formats and agendas and limits to the level of influence achieved. This paper reflects on the collective participation of young people in care in a rights-based initiative intended to facilitate input into service and policy development. This model, initiated by Tusla, Irelands Child and Family Agency, in partnership with EPIC an independent advocacy agency, provided an opportunity for young people in care to share direct experiences in order to identify and address challenges within the care system through meaningful collaborative processes. The perspectives of twenty-eight young participants were sought through five focus groups. In addition, twenty practitioners took part in semi-structured interviews. The design and analysis of these methods utilised a framework derived from Lundy s (2007) articulation of rights-based practice through the Voice Model . Key lessons emerging suggest that a strong policy and legislative frame for practice underpinned by a model that articulates the practice requirements for effective participation is promising as evidenced by the outputs of the collective model. However, evidence of influence on policy and the service delivery experienced by children in care remains to be seen, as this process requires further time and organisational resources to embed and assess. Moreover, there is a need for the further development of communicative structures and feedback mechanisms if it is to be experienced as meaningful by all young people who engage with the model. Despite challenges in practice and the time required to achieve transformative influence, the personal benefits of direct participation in the fora for young people are arguably a worthy outcome of participatory practice.This research was conducted as part of the Development and Mainstreaming Programme for Prevention, Partnership and Family Support Study, which is supported by the Atlantic Philanthropies Ireland; Galway University Foundation; the National University of Ireland, Galway.peer-reviewed2023-03-0