Modelling the Anatomic Distribution of Neurologic Events in Patients with COVID-19: A Systematic Review of MRI Findings.

BACKGROUND: Neurologic events have been reported in patients with coronavirus disease 2019 (COVID-19). However, a model-based evaluation of the spatial distribution of these events is lacking. PURPOSE: Our aim was to quantitatively evaluate whether a network diffusion model can explain the spread of small neurologic events. DATA SOURCES: The MEDLINE, EMBASE, Scopus, and LitCovid data bases were searched from January 1, 2020, to July 19, 2020. STUDY SELECTION: Thirty-five case series and case studies reported 317 small neurologic events in 123 unique patients with COVID-19. DATA ANALYSIS: Neurologic events were localized to gray or white matter regions of the Illinois Institute of Technology (gray-matter and white matter) Human Brain Atlas using radiologic images and descriptions. The total proportion of events was calculated for each region. A network diffusion model was implemented, and any brain regions showing a significant association (P < .05, family-wise error-corrected) between predicted and measured events were considered epicenters. DATA SYNTHESIS: Within gray matter, neurologic events were widely distributed, with the largest number of events (∼10%) observed in the bilateral superior temporal, precentral, and lateral occipital cortices, respectively. Network diffusion modeling showed a significant association between predicted and measured gray matter events when the spread of pathology was seeded from the bilateral cerebellum (r = 0.51, P < .001, corrected) and putamen (r = 0.4, P = .02, corrected). In white matter, most events (∼26%) were observed within the bilateral corticospinal tracts. LIMITATIONS: The risk of bias was not considered because all studies were either case series or case studies. CONCLUSIONS: Transconnectome diffusion of pathology via the structural network of the brain may contribute to the spread of neurologic events in patients with COVID-19.

The relationship of embolic particle size to patient outcomes in prostate artery embolisation for benign prostatic hyperplasia: a systematic review and meta-regression.

AIM: To explore the relationship of embolic particle size used in prostate artery embolisation (PAE) to patient outcomes. MATERIALS AND METHODS: A systematic review of PubMed, EMBASE, and the Cochrane database was undertaken to identify all existing studies using PAE for benign prostatic hyperplasia (BPH). Inclusion criteria included prospective studies reporting baseline and 12-month International Prostate Symptom Score (IPSS) and particle size. Exclusion criteria were overlapping studies, commentaries, abstracts, and letters. Data extraction from eligible studies included the size of embolic particle, particle material, and baseline and 12-month values for the following patient outcomes: IPSS, IPSS quality of life, urinary flow rate (Q-max), prostate volume, prostate specific antigen, and post-void residual volume. A meta-regression analysis was then undertaken to examine the relationship of particle size to patient outcome measures. RESULTS: Six studies with a total of 687 patients were identified. Meta-regression analysis demonstrated particle size as a statistically significant (p<0.001) moderator of 12-month IPSS change following PAE. No statistically significant relationships were identified with other patient outcome measures. CONCLUSION: Smaller embolic particle size is associated with a greater reduction in IPSS following PAE.

Cost-effectiveness of negative-pressure wound therapy in adults with severe open fractures of the lower limb: evidence from the WOLLF randomized controlled trial.

AIMS: The aim of this study was to estimate the cost-effectiveness of negative-pressure wound therapy (NPWT) in comparison with standard wound management after initial surgical wound debridement in adults with severe open fractures of the lower limb. PATIENTS AND METHODS: An economic evaluation was conducted from the perspective of the United Kingdom NHS and Personal Social Services, based on evidence from the 460 participants in the Wound Management of Open Lower Limb Fractures (WOLLF) trial. Economic outcomes were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Bivariate regression of costs (given in £, 2014 to 2015 prices) and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained associated with NPWT dressings. Sensitivity and subgroup analyses were undertaken to assess the impacts of uncertainty and heterogeneity, respectively, surrounding aspects of the economic evaluation. RESULTS: The base case analysis produced an incremental cost-effectiveness ratio of £267 910 per QALY gained, reflecting higher costs on average (£678; 95% confidence interval (CI) -£1082 to £2438) and only marginally higher QALYS (0.002; 95% CI -0.054 to 0.059) in the NPWT group. The probability that NPWT is cost-effective in this patient population did not exceed 27% regardless of the value of the cost-effectiveness threshold. This result remained robust to several sensitivity and subgroup analyses. CONCLUSION: This trial-based economic evaluation suggests that NPWT is unlikely to be a cost-effective strategy for improving outcomes in adult patients with severe open fractures of the lower limb. Cite this article: Bone Joint J 2019;101-B:1392-1401.

Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer.

RESEARCH QUESTION: An important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve? DESIGN: A prospective cohort study measured serum AMH in 66 young women with lymphoma and breast cancer, before and at 1 year and 5 years after chemotherapy, compared with 124 healthy volunteers of the same age range (18-43 years). Contemporaneously, patients reported their menses and live births during 5-year follow-up. RESULTS: After adjustment for age, serum AMH was 1.4 times higher (95% CI 1.1 to 1.9; P < 0.02) in healthy volunteers than in cancer patients before chemotherapy. A strong correlation was observed between baseline and 5-year AMH in the breast cancer group (P < 0.001, regression coefficient = 0.58, 95% CI 0.29 to 0.89). No significant association was found between presence of menses at 5 years and serum AMH at baseline (likelihood ratio test from logistics regression analysis). CONCLUSIONS: Reproductive-age women with malignancy have lower serum AMH than healthy controls even before starting chemotherapy. Pre-chemotherapy AMH was significantly associated with long-term ovarian function in women with breast cancer. At key time points, AMH measurements could be used as a reproductive health advisory tool for young women with cancer. Our results highlight the unsuitability of return of menstruation as a clinical indicator of ovarian reserve after chemotherapy.

Percutaneous fixation with Kirschner wires versus volar locking-plate fixation in adults with dorsally displaced fracture of distal radius: five-year follow-up of a randomized controlled trial.

AIMS: The aim of this study was to compare the clinical effectiveness of Kirschner wire (K-wire) fixation with locking-plate fixation for patients with a dorsally displaced fracture of the distal radius in the five years after injury. PATIENTS AND METHODS: We report the five-year follow-up of a multicentre, two-arm, parallel-group randomized controlled trial. A total of 461 adults with a dorsally displaced fracture of the distal radius within 3 cm of the radiocarpal joint that required surgical fixation were recruited from 18 trauma centres in the United Kingdom. Patients were excluded if the surface of the wrist joint was so badly displaced it required open reduction. In all, 448 patients were randomized to receive either K-wire fixation or locking-plate fixation. In the K-wire group, there were 179 female and 38 male patients with a mean age of 59.1 years (19 to 89). In the locking-plate group, there were 194 female and 37 male patients with a mean age of 58.3 years (20 to 89). The primary outcome measure was the patient-rated wrist evaluation (PRWE). Secondary outcomes were health-related quality of life using the EuroQol five-dimension three-level (EQ-5D-3L) assessment, and further surgery related to the index fracture. RESULTS: At 12 months, 402/448 participants (90%) recruited into the main study provided PRWE scores. At year two, 294 participants (66%) provided scores; at year five, 198 participants (44%) provided scores. There was no clinically relevant difference in the PRWE at any point during the five-year follow-up; at five years, the PRWE score was 8.3 (12.5) in the wire group and 11.3 (15.6) in the plate group (95% confidence interval -6.99 to 0.99; p = 0.139). Nor was there a clinically relevant difference in health-related quality of life. Only three participants had further surgery in the five years after their injury (one in the wire group and two in the plate group). CONCLUSION: This follow-up study continues to show no evidence of a difference in wrist pain, wrist function, or quality of life for patients treated with wires versus locking plates in the five years following a dorsally displaced fracture of the distal radius. Cite this article: Bone Joint J 2019;101-B:978-983.

Validation of a prospective cohort study of older adults with hip fractures.

AIMS: This study sought to determine the proportion of older adults with hip fractures captured by a multicentre prospective cohort, the World Hip Trauma Evaluation (WHiTE), whether there was evidence of selection bias during WHiTE recruitment, and the extent to which the WHiTE cohort is representative of the broader population of older adults with hip fractures. PATIENTS AND METHODS: The characteristics of patients recruited into the WHiTE cohort study were compared with those treated at WHiTE hospitals during the same timeframe and submitted to the National Hip Fracture Database (NHFD). RESULTS: Patients recruited to WHiTE were more likely to be admitted from their own home (83.5% vs 80.2%; p < 0.001) and to have a higher median Abbreviated Mental Test Score (AMTS) (9 (interquartile range (IQR) 6 to 10) vs 9 (IQR 5 to 10); p < 0.001) than those who were not recruited. In terms of WHiTE cohort generalizability, participating hospitals included a greater proportion of Major Trauma Centres (47.8% vs 7.8%) and large hospitals (997 (IQR 873 to 1290) vs 707 (459 to 903) beds) with high-volume Emergency Departments (median annual attendances of 43 981 (IQR 37 147 to 54 385) vs 35 964 (IQR 26 229 to 50 551)). However, there were few differences in baseline characteristics between patients in the WHiTE cohort and those recorded in the NHFD. CONCLUSION: There is evidence of a weak selection bias towards recruiting fitter patients within the WHiTE cohort, which will help to put into context the findings of future studies. We conclude that the patients within the WHiTE cohort are representative of the national population of older adults with hip fractures throughout England, Wales, and Northern Ireland. Cite this article: Bone Joint J 2019;101-B:708-714.

The Avon patellofemoral joint arthroplasty: two- to 18-year results of a large single-centre cohort.

Aims: This study reports on the medium- to long-term implant survivorship and patient-reported outcomes for the Avon patellofemoral joint (PFJ) arthroplasty. Patients and Methods: A total of 558 Avon PFJ arthroplasties in 431 patients, with minimum two-year follow-up, were identified from a prospective database. Patient-reported outcomes and implant survivorship were analyzed, with follow-up of up to 18 years. Results: Outcomes were recorded for 483 implants (368 patients), representing an 86% follow-up rate. The median postoperative Oxford Knee Score (0 to 48 scale) was 35 (interquartile range (IQR) 25.5 to 43) and the median Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, 0 to 100 scale) was 35 (IQR 25 to 53) at two years. There were 105 revisions, 61 (58%) for progression of osteoarthritis. All documented revisions were to primary knee systems without augmentation. The implant survival rate was 77.3% (95% confidence interval (CI) 72.4 to 81.7, number at risk 204) at ten years and 67.4% (95% CI 72.4 to 81.7 number at risk 45) at 15 years. Regression analysis of explanatory data variable showed that cases performed in the last nine years had improved survival compared with the first nine years of the cohort, but the individual operating surgeon had the strongest effect on survivorship. Conclusion: Satisfactory long-term results can be obtained with the Avon PFJ arthroplasty, with maintenance of patient-reported outcome measures (PROMs), satisfactory survival, and low rates of loosening and wear. Cite this article: Bone Joint J 2018;100-B:1162-7.

A comparison of the cost-effectiveness of intramedullary nail fixation and locking plate fixation in the treatment of adult patients with an extra-articular fracture of the distal tibia: economic evaluation based on the FixDT trial.

Aims: The aim of this study was to compare the cost-effectiveness of intramedullary nail fixation and 'locking' plate fixation in the treatment of extra-articular fractures of the distal tibia. Patients and Methods: An economic evaluation was conducted from the perspective of the United Kingdom National Health Service (NHS) and personal social services (PSS), based on evidence from the Fixation of Distal Tibia Fractures (UK FixDT) multicentre parallel trial. Data from 321 patients were available for analysis. Costs were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality adjusted life year (QALY) gained, and net monetary benefit. Sensitivity analyses were conducted to test the robustness of cost-effectiveness estimates. Results: Mean NHS and PSS costs were significantly lower for patients treated with an intramedullary nail than for those treated with a locking plate (-£970, 95% confidence interval (CI) -1685 to -256; p = 0.05). There was a small increase in QALYs gained in the nail fixation group (0.01, 95% CI -0.03 to 0.06; p = 0.52). The probability of cost-effectiveness for nail fixation exceeded 90% at cost-effectiveness thresholds as low as £15 000 per additional QALY. The cost-effectiveness results remained robust to several sensitivity analyses. Conclusion: This trial-based economic evaluation suggests that nail fixation is a cost-effective alternative to locking plate fixation. Cite this article: Bone Joint J 2018;100-B:624-33.

The effect of triclosan-coated sutures on the rate of surgical site infection after hip and knee arthroplasty: a double-blind randomized controlled trial of 2546 patients.

Aims: Surgical site infection (SSI) is a common complication of surgery with an incidence of about 1% in the United Kingdom. Sutures can lead to the development of a SSI, as micro-organisms can colonize the suture as it is implanted. Triclosan-coated sutures, being antimicrobical, were developed to reduce the rate of SSI. Our aim was to assess whether triclosan-coated sutures cause a reduction in SSIs following arthroplasty of the hip and knee. Patients and Methods: This two-arm, parallel, double-blinded study involved 2546 patients undergoing elective total hip (THA) and total knee arthroplasty (TKA) at three hospitals. A total of 1323 were quasi-randomized to a standard suture group, and 1223 being quasi-randomized to the triclosan-coated suture group. The primary endpoint was the rate of SSI at 30 days postoperatively. Results: The baseline characteristics of age, gender and comorbidities were well matched in the two groups. The rates of superficial SSI were 0.8% in the control group and 0.7% in the intervention group (p = 0.651), and when deep and superficial SSIs were combined the rates were 2.5% and 1.8 (p = 0.266). The length of stay in hospital and the rates of medical complications did not differ significantly between the groups (p = 1.000). Conclusion: This trial provided no evidence that the use of triclosan-coated sutures at THA and TKA leads to a reduction in the rate of SSI. Cite this article: Bone Joint J 2018;100-B:296-302.

A randomized controlled trial comparing the Thompson hemiarthroplasty with the Exeter polished tapered stem and Unitrax modular head in the treatment of displaced intracapsular fractures of the hip: the WHiTE 3: HEMI Trial.

Aims: This study aimed to compare the change in health-related quality of life of patients receiving a traditional cemented monoblock Thompson hemiarthroplasty compared with a modern cemented modular polished-taper stemmed hemiarthroplasty for displaced intracapsular hip fractures. Patients and Methods: This was a pragmatic, multicentre, multisurgeon, two-arm, parallel group, randomized standard-of-care controlled trial. It was embedded within the WHiTE Comprehensive Cohort Study. The sample size was 964 patients. The setting was five National Health Service Trauma Hospitals in England. A total of 964 patients over 60 years of age who required hemiarthroplasty of the hip between February 2015 and March 2016 were included. A standardized measure of health outcome, the EuroQol (EQ-5D-5L) questionnaire, was carried out on admission and at four months following the operation. Results: Of the 964 patients enrolled, 482 died or were lost to follow-up (50%). No significant differences were noted in EQ-5D between groups, with a mean difference at four months of 0.037 in favour of the Exeter/Unitrax implant (95% confidence interval (CI) 0.014 to 0.087, p = 0.156), rising to 0.045 (95% CI 0.007 to 0.098, p = 0.09) when patients who died were excluded. The minimum clinically important difference for EQ-5D-5L used in this study is 0.08, therefore any benefit between implants is unlikely to be noticeable to the patient. There was no difference in mortality or mobility score. Conclusion: Allowing for the high rate of loss to follow-up, the use of the traditional Thompson hemiarthroplasty in the treatment of the displaced intracapsular hip fracture shows no difference in health outcome when compared with a modern cemented hemiarthroplasty. Cite this article: Bone Joint J 2018;100-B:352-60.

A pilot randomized trial of meniscal allograft transplantation versus personalized physiotherapy for patients with a symptomatic meniscal deficient knee compartment.

AIMS: Meniscal allograft transplantation is undertaken to improve pain and function in patients with a symptomatic meniscal deficient knee compartment. While case series have shown improvements in patient reported outcome measures (PROMs), its efficacy has not been rigorously evaluated. This study aimed to compare PROMs in patients having meniscal transplantation with those having personalized physiotherapy at 12 months. PATIENTS AND METHODS: A single-centre assessor-blinded, comprehensive cohort study, incorporating a pilot randomized controlled trial (RCT) was performed on patients with a symptomatic compartment of the knee in which a (sub)total meniscectomy had previously been performed. They were randomized to be treated either with a meniscal allograft transplantation or personalized physiotherapy, and stratified for malalignment of the limb. They entered the preference groups if they were not willing to be randomized. The Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score and Lysholm score and complications were collected at baseline and at four, eight and 12 months following the interventions. RESULTS: A total of 36 patients entered the study; 21 were randomized and 15 chose their treatments. Their mean age was 28 years (range 17 to 46). The outcomes were similar in the randomized and preference groups, allowing pooling of data. At 12 months, the KOOS4 composite score (mean difference 12, p = 0.03) and KOOS subscales of pain (mean difference 15, p = 0.02) and activities of daily living (mean difference 18, p = 0.005) were significantly superior in the meniscal transplantation group. Other PROMs also favoured this group without reaching statistical significance. There were five complications in the meniscal transplantation and one in the physiotherapy groups. CONCLUSION: This is the first study to compare meniscal allograft transplantation to non-operative treatment. The results provide the best quality evidence to date of the symptomatic benefits of meniscal allograft transplantation in the short term, but a multicentre RCT is required to investigate this question further. Cite this article: Bone Joint J 2018;100-B:56-63.

Modelling and estimation of health-related quality of life after hip fracture: A re-analysis of data from a prospective cohort study.

OBJECTIVES: This study investigates the reporting of health-related quality of life (HRQoL) in patients following hip fracture. We compare the relative merits and make recommendations for the use for two methods of measuring HRQoL; (i) including patients who died during follow-up and (ii) including survivors only. METHODS: The World Hip Trauma Evaluation has previously reported changes in HRQoL using EuroQol-5D for patients with hip fractures. We performed additional analysis to investigate the effect of including or excluding those patients who died during the first four months of the follow-up period. RESULTS: The dataset included 503 patients, 25 of whom died between 30 days and four months of injury. There was a statistically significant difference in 30-day HRQoL between those alive (mean 0.331 and standard deviation (sd) 0.360) and those dead (mean 0.156 and sd 0.421) by four months (independent-samples t-test; p 0.022). The estimated difference of 0.175 in HRQoL (95% confidence interval 0.025 to 0.325) was also highly clinically significant. CONCLUSION: When reporting HRQoL for patients after a hip fracture, excluding patients who die during follow-up leads to an overestimate of the effects of the intervention or treatment pathway. We would recommend that death-adjusted estimates should be used routinely when reporting HRQoL in this population.Cite this article: N. Parsons, X. L. Griffin, J. Achten, T. J. Chesser, S. E. Lamb, M. L. Costa. Modelling and estimation of health-related quality of life after hip fracture: A re-analysis of data from a prospective cohort study. Bone Joint Res 2018;7:1-5.

A pragmatic randomised controlled trial comparing the efficacy of a femoral nerve block and periarticular infiltration for early pain relief following total knee arthroplasty.

AIMS: The aim of this study was to compare the effectiveness of a femoral nerve block and a periarticular infiltration in the management of early post-operative pain after total knee arthroplasty (TKA). PATIENTS AND METHODS: A pragmatic, single centre, two arm parallel group, patient blinded, randomised controlled trial was undertaken. All patients due for TKA were eligible. Exclusion criteria included contraindications to the medications involved in the study and patients with a neurological abnormality of the lower limb. Patients received either a femoral nerve block with 75 mg of 0.25% levobupivacaine hydrochloride around the nerve, or periarticular infiltration with 150 mg of 0.25% levobupivacaine hydrochloride, 10 mg morphine sulphate, 30 mg ketorolac trometamol and 0.25 mg of adrenaline all diluted with 0.9% saline to make a volume of 150 ml. RESULTS: A total of 264 patients were recruited and data from 230 (88%) were available for the primary analysis. Intention-to-treat analysis of the primary outcome measure of a visual analogue score for pain on the first post-operative day, prior to physiotherapy, was similar in both groups. The mean difference was -0.7 (95% confidence interval (CI) -5.9 to 4.5; p = 0.834). The periarticular group used less morphine in the first post-operative day compared with the femoral nerve block group (74%, 95% CI 55 to 99). The femoral nerve block group reported 39 adverse events, of which 27 were serious, in 31 patients and the periarticular group reported 51 adverse events, of which 38 were serious, in 42 patients up to six weeks post-operatively. None of the adverse events were directly attributed to either of the interventions under investigation. CONCLUSION: Periarticular infiltration is a viable and safe alternative to femoral nerve block for the early post-operative relief of pain following TKA. Cite this article: Bone Joint J 2017;99-B:904-11.

The tip-apex distance in the X-Bolt dynamic plating system.

OBJECTIVES: The Sliding Hip Screw (SHS) is commonly used to treat trochanteric hip fractures. Fixation failure is a devastating complication requiring complex revision surgery. One mode of fixation failure is lag screw cut-out which is greatest in unstable fracture patterns and when the tip-apex distance of the lag screw is > 25 mm. The X-Bolt Dynamic Hip Plating System (X-Bolt Orthopaedics, Dublin, Ireland) is a new device which aims to reduce this risk of cut-out. However, some surgeons have reported difficulty minimising the tip-apex distance with subsequent concerns that this may lead to an increased risk of cut-out. PATIENTS AND METHODS: We measured the tip-apex distance from the intra-operative radiographs of 93 unstable trochanteric hip fractures enrolled in a randomised controlled trial (Warwick Hip Trauma Evaluation, WHiTE One trial). Participants were treated with either the sliding hip screw or the X-Bolt dynamic hip plating system. We also recorded the incidence of cut-out in both groups, at a median follow-up time of 17 months. RESULTS: There was a significantly increased tip-apex distance with the use of the X-Bolt (mean difference 3.7mm (95% confidence interval 1.58 to 5.73); SHS mean 17.1 mm, X-Bolt mean 20.8; p = 0.001. However, this was not associated with an increased incidence of cut-out at a median follow-up time of 17 months, with three cut-outs (6%) in the SHS group and 0 (0%) in the X-Bolt group. CONCLUSION: The X-Bolt is a safe implant with no increased risk for cut-out. Concerns about minimising the tip-apex distance may be justified but do not appear to be clinically important.Cite this article: M. A. Fernandez, A. Aquilina, J. Achten, N. Parsons, M. L. Costa, X. L. Griffin. The tip-apex distance in the X-Bolt dynamic plating system. Bone Joint Res 2017;6:-207. DOI: 10.1302/2046-3758.64.BJR-2015-0016.R2.