Comparison of surgical or non-surgical management for non-acute anterior cruciate ligament injury: the ACL SNNAP RCT.

Background: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. Objective(s): To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Design: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Setting: Twenty-nine NHS orthopaedic units in the United Kingdom. Participants: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Interventions: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. Main outcome measures: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Results: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively. Limitations: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. Conclusions: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation. Future work: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful. Trial registration: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367. Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.

The study aimed to find out whether it is better to offer surgical reconstruction or rehabilitation first to patients with a more long-standing injury of their anterior cruciate ligament in their knee. This injury causes physical giving way of the knee and/or sensations of it being wobbly (instability). The instability can affect daily activities, work, sport and can lead to arthritis. There are two main treatment options for this problem: non-surgical rehabilitation (prescribed exercises and advice from physiotherapists) or an operation by a surgeon to replace the damaged ligament (anterior cruciate ligament reconstruction). Although studies have highlighted the best option for a recently injured knee, the best management was not known for patients with a long-standing injury, perhaps occurring several months previously. Because the surgery is expensive to the NHS (around £100 million per year), it was also important to look at the costs involved. We carried out a study recruiting 316 non-acute anterior cruciate ligament-injured patients from 29 different hospitals and allocated each patient to either surgery or rehabilitation as their treatment option. We measured how well they did with special function and activity scores, patient satisfaction and costs of treatment. Patients in both groups improved substantially. It was expected that some patients in the rehabilitation group would want surgery if non-surgical management was unsuccessful. Forty-one per cent of patients who initially underwent rehabilitation subsequently elected to have reconstructive surgery. Overall, the patients allocated to the surgical reconstruction group had better results in terms of knee function and stability, activity level and satisfaction with treatment than patients allocated to the non-operative rehabilitation group. There were few problems or complications with either treatment option. Although the surgery was a more expensive treatment option, it was found to be cost-effective in the UK setting. The evidence can be discussed in shared decision-making with anterior cruciate ligament-injured patients. Both strategies of management led to improvement. Although a rehabilitation strategy can be beneficial, especially for recently injured patients, it is advised that later-presenting non-acute and more long-standing anterior cruciate ligament-injured patients undergo surgical reconstruction without necessarily delaying for a period of rehabilitation.

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

BACKGROUND: Anterior 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. METHODS: We 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. FINDINGS: Between 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. INTERPRETATION: Surgical 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. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

Deep Brain Stimulation for Recovery of Consciousness in Minimally Conscious Patients After Traumatic Brain Injury: A Systematic Review.

OBJECTIVES: Minimally conscious state (MCS) is a disorder of consciousness in which minimal but definite behavioral evidence of self-awareness or environmental awareness is demonstrated. Deep brain stimulation (DBS) of various targets has been used to promote recovery in patients with disorders of consciousness with varying results. The aim of this systematic review was to assess the effects of DBS in MCS following traumatic brain injury (TBI). MATERIALS AND METHODS: A systematic literature review was carried out using a number of electronic bibliographic data bases to identify relevant studies. We included all studies describing applications of DBS on patients in MCS following TBI. RESULTS: Eight studies were identified, including a total of ten patients, aged 15-58 years. The time from injury to stimulation ranged from 3 to 252 months, with the duration of follow-up post-DBS ranging from 10 to 120 months. Seven patients improved their postsurgical outcome score measures (three patients with the coma recovery scale, one with the near coma scale, and three with the Glasgow outcome score). A descriptive favorable outcome was reported in one patient. Two patients were reported not to have shown any improvements following the intervention. CONCLUSIONS: Current evidence is based on a small population of heterogeneous patients. The time from injury to stimulation was significantly variable and problematic, as spontaneous recovery can occur within the first year of injury. Although seven patients showed promising results in validated outcome measures, evidence supporting the use of DBS in MCS patients following TBI is lacking. There is need for controlled and randomized studies.

GBA-Associated Parkinson's Disease: Progression in a Deep Brain Stimulation Cohort.

BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.