Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Perioperative interventions to improve early mobilisation and physical function after hip fracture: a systematic review and meta-analysis.

BACKGROUND: Perioperative interventions could enhance early mobilisation and physical function after hip fracture surgery. OBJECTIVE: Determine the effectiveness of perioperative interventions on early mobilisation and physical function after hip fracture. METHODS: Ovid MEDLINE, CINAHL, Embase, Scopus and Web of Science were searched from January 2000 to March 2022. English language experimental and quasi-experimental studies were included if patients were hospitalised for a fractured proximal femur with a mean age 65 years or older and reported measures of early mobilisation and physical function during the acute hospital admission. Data were pooled using a random effect meta-analysis. RESULTS: Twenty-eight studies were included from 1,327 citations. Studies were conducted in 26 countries on 8,192 participants with a mean age of 80 years. Pathways and models of care may provide a small increase in early mobilisation (standardised mean difference [SMD]: 0.20, 95% confidence interval [CI]: 0.01-0.39, I2 = 73%) and physical function (SMD: 0.07, 95% CI 0.00 to 0.15, I2 = 0%) and transcutaneous electrical nerve stimulation analgesia may provide a moderate improvement in function (SMD: 0.65, 95% CI: 0.24-1.05, I2 = 96%). The benefit of pre-operative mobilisation, multidisciplinary rehabilitation, recumbent cycling and clinical supervision on mobilisation and function remains uncertain. Evidence of no effect on mobilisation or function was identified for pre-emptive analgesia, intraoperative periarticular injections, continuous postoperative epidural infusion analgesia, occupational therapy training or nutritional supplements. CONCLUSIONS: Perioperative interventions may improve early mobilisation and physical function after hip fracture surgery. Future studies are needed to model the causal mechanisms of perioperative interventions on mobilisation and function after hip fracture.

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. Trial Registration: ANZCTR Identifier: ACTRN12618001879257.

Outcome of paediatric acute flaccid myelitis associated with enterovirus D68: a case series.

Enterovirus D68 (EV-D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV-D68 infection have increased in recent years and the evidence for a causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV-D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2-6y) from South East Scotland during September and October 2016 after infection with EV-D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18-month follow-up, two cases remain ventilator-dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV-D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18-month outcome will help clinicians to counsel families. WHAT THIS PAPER ADDS: Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases. Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.

Patient, surgical and hospital factors predicting actual first-day mobilisation after hip fracture surgery: An observational cohort study.

OBJECTIVES: To examine patient, surgical and hospital factors associated with Day-1 postoperative mobility after hip fracture surgery in older adults. METHODS: A cohort study using Australia and New Zealand Hip Fracture Registry was conducted. Participants were aged older than 50 years and underwent hip fracture surgery between 1 January 2020 and 31 December 2020 inclusive. The outcome was standing and step transferring out of bed onto a chair and/or walking Day-1 after hip fracture surgery. RESULTS: Mean age was 82 years and 68% were women. Of 12,318 patients with hip fracture, 5981 (49%) actually mobilised Day-1. Odds of actual first-day mobilisation were lower for individuals usually walking with either stick or crutch (OR = 0.71, 95% CI 0.62-0.82) or two aids or frame (OR = 0.57, 95% CI 0.52-0.64) or wheelchair/bed bound (OR = 0.24, 95% CI 0.17-0.33); who had impaired cognition preadmission (OR = 0.57, 95% CI 0.51-0.64); from aged care facilities (OR = 0.59, 95% CI 0.52-0.67); had an American Society of Anaesthesiologists grade 2 (OR = 0.63, 95% CI 0.41-0.97), 3 (OR = 0.31, 95% CI 0.20-0.47) or 4 or 5 (OR = 0.21, 95% CI 0.14-0.32); surgery delay >48 h (OR = 0.81, 95% CI 0.71-0.91); and restricted/non-weight-bearing status immediately postoperatively (OR = 0.53, 95% CI 0.42-0.67). CONCLUSIONS: Both non-modifiable and modifiable patient and surgical factors influence first-day mobilisation after hip fracture surgery. Reducing time to surgery might assist future quality improvement efforts to increase Day-1 postoperative mobility.

Improving hip fracture care: A five-year review of the early contributors to the Australian and New Zealand Hip Fracture Registry.

OBJECTIVE: The aim of this study was to examine temporal trends (2016-2020) in hip fracture care in Australian and New Zealand (ANZ) hospitals that started providing patient-level data to the ANZ Hip Fracture Registry (ANZHFR) on/before 1 January 2016 (early contributors). METHODS: Retrospective cohort study of early contributor hospitals (n = 24) to the ANZHFR. The study cohort included patients aged ≥50 years admitted with a low trauma hip fracture between 1 January 2016 and 31 December 2020 (n = 26,937). Annual performance against 11 quality indicators and 30- and 365-day mortality were examined. RESULTS: Compared to 2016/2017, year-on-year improvements were demonstrated for preoperative cognitive assessment (2020: OR 3.57, 95% confidence interval [95% CI] 3.29-3.87) and nerve block use prior to surgery (2020: OR 4.62, 95% CI 4.17-5.11). Less consistent improvements over time from 2016/2017 were demonstrated for emergency department (ED) stay of <4 h (2017; 2020), pain assessment ≤30 min of ED presentation (2020), surgery ≤48 h (2020) and bone protection medication prescribed on discharge (2017-2020; 2020 OR 2.22, 95% CI 2.03-2.42). The odds of sustaining a hospital-acquired pressure injury increased in 2019-2020 compared to 2016. The odds of receiving an orthogeriatric model of care and being offered the opportunity to mobilise on Day 1 following surgery fluctuated. There was a reduction in 365-day mortality in 2020 compared to 2016 (OR 0.86, 95% CI 0.74-0.98), whereas 30-day mortality did not change. CONCLUSIONS: Several quality indicators improved over time in early contributor hospitals. Indicators that did not improve may be targets for future care improvement activities, including considering incentivised hip fracture care, which has previously been shown to improve care/outcomes. COVID-19 and reporting practices may have impacted the study findings.

Complications related to therapeutic anticoagulation in total hip arthroplasty.

Bleeding-related wound complications cause significant morbidity in lower limb arthroplasty surgery. Patients who require therapeutic anticoagulation in the perioperative period are potentially at higher risk for these complications. This is a retrospective case-control study reviewing all primary total hip arthroplasties performed in a single center during a 5-year period and comparing outcomes of the patients on warfarin with a double-matched control group of patients not on warfarin. The warfarin group had a significantly higher risk of deep joint infection (9% vs 2.2%), hematoma/wound ooze (28% vs 4%), and superficial infection (13.5% vs 2.2%). Managing patients undergoing total hip arthroplasty with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding-related complications. Improved understanding of this risk will better allow patients to make an informed decision regarding their elective arthroplasty surgery.

Comparing outcomes of total hip arthroplasty versus hemiarthroplasty in neck of femur fracture patients: an Australian registry study.

PURPOSE: To determine discharge outcomes of displaced subcapital NOF patients who were from home, with intact pre-operative cognition, ASA 1 or 2 and independent walkers treated with either THA or hemiarthroplasty. METHODS: A retrospective registry study was performed using data from the Australia and New Zealand Hip Fracture Registry (ANZHFR). Institutional ethics approval was obtained prior to commencement. Hip fracture registry records between 1st January 2016 and 31st January 2020 were reviewed. RESULTS: A total of 930 patients with complete records were identified and included. There were 602 THA and 328 hemiarthroplasty patients. Using multivariate analysis, pre-operative factors associated with THA include younger age (OR = 0.90 for every year older, p < 0.001), females (p = 0.043), private admissions (OR = 1.62, p = 0.028) and receiving pre-operative geriatric assessment (OR = 1.89, p = 0.002). Delay to theatre due to not being fit for surgery was associated with not receiving THA (OR = 0.21, p < 0.001). THA resulted in a shorter total hospital length of stay (MD = 7.24, p < 0.001), higher likelihood of being discharged home (OR = 1.88, p < 0.001) and lower likelihood of being discharged to a residential aged care facility (OR = 0.32, p = 0.019). CONCLUSION: Displaced subcapital NOF patients who were admitted from home, had intact pre-operative cognition, ASA 1 or 2, independent walkers and had THAs, had shorter total hospital length of stay, were more likely to be discharged home directly and less likely to end up in residential aged care facilities compared to those undergoing hemiarthroplasty.

Effect of Aspirin vs Enoxaparin on 90-Day Mortality in Patients Undergoing Hip or Knee Arthroplasty: A Secondary Analysis of the CRISTAL Cluster Randomized Trial.

Importance: Ischemic heart disease remains the leading cause of mortality following hip and knee arthroplasty. Due to its antiplatelet and cardioprotective properties, aspirin has been proposed as an agent that could reduce mortality when used as venous thromboembolism (VTE) prophylaxis following these procedures. Objective: To compare aspirin with enoxaparin in reducing 90-day mortality for patients undergoing hip or knee arthroplasty procedures. Design, Setting, and Participants: This study was a planned secondary analysis of the CRISTAL cluster randomized, crossover, registry-nested trial performed across 31 participating hospitals in Australia between April 20, 2019, and December 18, 2020. The aim of the CRISTAL trial was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE following hip or knee arthroplasty. The primary study restricted the analysis to patients undergoing total hip or knee arthroplasty for a diagnosis of osteoarthritis only. This study includes all adult patients (aged ≥18 years) undergoing any hip or knee arthroplasty procedure at participating sites during the course of the trial. Data were analyzed from June 1 to September 6, 2021. Interventions: Hospitals were randomized to administer all patients oral aspirin (100 mg daily) or subcutaneous enoxaparin (40 mg daily) for 35 days after hip arthroplasty and 14 days after knee arthroplasty procedures. Main Outcomes and Measures: The primary outcome was mortality within 90 days. The between-group difference in mortality was estimated using cluster summary methods. Results: A total of 23 458 patients from 31 hospitals were included, with 14 156 patients allocated to aspirin (median [IQR] age, 69 [62-77] years; 7984 [56.4%] female) and 9302 patients allocated to enoxaparin (median [IQR] age, 70 [62-77] years; 5277 [56.7%] female). The mortality rate within 90 days of surgery was 1.67% in the aspirin group and 1.53% in the enoxaparin group (estimated difference, 0.04%; 95% CI, -0.05%-0.42%). For the subgroup of 21 148 patients with a nonfracture diagnosis, the mortality rate was 0.49% in the aspirin group and 0.41% in the enoxaparin group (estimated difference, 0.05%; 95% CI, -0.67% to 0.76%). Conclusions and Relevance: In this secondary analysis of a cluster randomized trial comparing aspirin with enoxaparin following hip or knee arthroplasty, there was no significant between-group difference in mortality within 90 days when either drug was used for VTE prophylaxis. Trial Registration: http://anzctr.org.au Identifier: ACTRN12618001879257.

Knowledge of Musculoskeletal Medicine in Junior Doctors in Australia: Is It Adequate?

Purpose: The incidence of musculoskeletal disease is increasing in Australia and around the world. However, medical student education does not necessarily reflect current and projected trends in musculoskeletal medicine. The aim of this study was to assess junior doctors' competency in musculoskeletal medicine using the Freedman and Bernstein Basic Competency Examination in Musculoskeletal Medicine questionnaire. Methods: We conducted a cohort study of interns (first year post medical school) across four teaching hospitals in Australia. Interns were asked to take the Freedman and Bernstein examination during organised intern teaching sessions, and results were analysed using the original Freedman and Bernstein marking criteria and validated pass mark. Results: The mean score for the 92 interns was 13.9 out of 25 (55%) with scores ranging from 8 to 20.8 (29-83%). Only 8 of the 92 interns (8.7%) achieved a score of greater than 73%, the pre-specified pass mark. Conclusion: Our study identifies inadequacies in musculoskeletal medical knowledge in Australian interns. Review of undergraduate medical education may be required to reflect current and predicted trends in the prevalence of musculoskeletal disease and adequately prepare junior doctors.

Obesity and the Risk of Venous Thromboembolism after Major Lower Limb Orthopaedic Surgery: A Literature Review.

The risk of venous thromboembolism following total joint arthroplasty is significantly greater than those of other types of elective orthopaedic procedures. This risk is increased in obesity due to the associated prothrombotic physiological and hematological changes that predispose to embolic events. The prevalence of obesity is increasing in the aging population, which contributes to a further increase in the risk of postoperative thrombosis in the older patients. There is a lack of clear evidence regarding dosing information for thromboprophylaxis medications in patients with obesity. As a result, the currently available thromboprophylaxis guidelines do not provide specific recommendations for this group. Suboptimal dosing regimens for these medications can place these patients at a risk of bleeding or clotting complications postsurgery. Hence any increase in dosage may require intensive surveillance for the residual anticoagulant effects and careful balancing of risks and benefits on an individual basis. Our review discusses the basis for increased thrombotic risk in obesity, the evidence supporting dosage recommendations, and the implications of the current guidelines for pharmacological thromboprophylaxis in patients with obesity undergoing lower limb arthroplasty.

Two-country comparison of the prescription of bone protection medication before and early after hip fracture.

Pharmacological management of bone health warrants investigation into factors influencing initiation of bone protection medication (BPM) at discharge after a hip fracture. This sprint audit identified reasons attributed to low BPM treatment levels at hospital discharge which can guide improvement in the prevention of future fractures. PURPOSE: To compare patient characteristics and Australian and New Zealand approaches to prescribing bone protection medication (BPM) pre- or post-hip fracture, determine reasons why BPM was not prescribed earlier post-fracture, and assess the generalisability of sprint audit and the Australian and New Zealand Hip Fracture Registry (ANZHFR) patient cohorts. METHODS: A retrospective cohort study of hip fracture patients from the ANZHFR aged ≥ 50 years (2016-2020) and consecutive patients from the 2021 BPM sprint audit. Multivariable logistic regression was used to examine factors associated with not prescribing BPM. RESULTS: Of 55,618 patients admitted with a hip fracture in the ANZHFR, less than 10% of patients in Australia and New Zealand were taking BPM on admission, increasing to 22.4% in Australia and 27.8% in New Zealand on discharge. Registry patients who were younger (50-69 years), healthy (ASA grade 1), lived in a residential aged care facility, had impaired cognition, delirium identified, or were awaiting a specialist falls assessment were less likely to take BPM. Within the audit, 46.2% of patients in Australia and 39.2% in New Zealand did not have BPM in their discharge prescription. The most common reason for not prescribing BPM in Australia was low level of vitamin D (13.3%), and in New Zealand, renal impairment (14.8%). Sprint and registry patient characteristics were comparable in terms of patient age, sex, usual place of residence, and ASA grade. CONCLUSIONS: BPM prescription early after hip fracture is low. Opportunities exist to increase the rate of prescription of medications known to prevent future fractures in this high-risk population.

A desirability of outcome ranking (DOOR) for periprosthetic joint infection - a Delphi analysis.

Background: Treatment outcomes in studies on prosthetic joint infection are generally assessed using a dichotomous outcome relating to treatment success or failure. These outcome measures neither include patient-centred outcome measures including joint function and quality of life, nor do they account for adverse effects of treatment. A desirability of outcome ranking (DOOR) measure can include these factors and has previously been proposed and validated for other serious infections. We aimed to develop a novel DOOR for prosthetic joint infections (PJIs). Methods: The Delphi method was used to develop a DOOR for PJI research. An international working group of 18 clinicians (orthopaedic surgeons and infectious disease specialists) completed the Delphi process. The final DOOR comprised the dimensions established to be most important by consensus with > 75  % of participant agreement. Results: The consensus DOOR comprised four main dimensions. The primary dimension was patient-reported joint function. The secondary dimensions were infection cure and mortality. The final dimension of quality of life was selected as a tie-breaker. Discussion: A desirability of outcome ranking for periprosthetic joint infection has been proposed. It focuses on patient-centric outcome measures of joint function, cure and quality of life. This DOOR provides a multidimensional assessment to comprehensively rank outcomes when comparing treatments for prosthetic joint infection.

Reactive Arthritis from Influenza Vaccination: A Novel Presentation That Mimics Prosthetic Joint Infection: A Case Report.

CASE: A 50-year-old woman with a history of bilateral knee replacements developed acute-onset bilateral painful knee effusions and inability to weight-bear. She was systemically well, but 2 days before the onset of her symptoms, she received an influenza vaccination. Synovial fluid analysis revealed white cell count (WCC) 190,000 × 109, 85% polymorphomuclear lymphocytes (PMN) on the left knee and WCC 252,200 × 109, 89% PMN on the right knee. Debridement and implant retention and polyethylene exchange was performed. Extended bacterial culture was negative as was 16s RNA polymerase chain reaction for remnants of bacterial DNA. No crystals were seen on any specimen. Both knees are stable and pain free at 12-month follow-up. CONCLUSION: Reactive arthritis secondary to influenza vaccination is a rare condition that can mimic prosthetic joint infection.

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study.

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016-2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016-2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.

Face Coverings, Aerosol Dispersion and Mitigation of Virus Transmission Risk.

The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. Face covers can mitigate the risk of virus transmission but their outward effectiveness is not fully ascertained. Objective: by using a background oriented schlieren technique, we aim to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. Results: we found that all face covers without an outlet valve reduce the front flow through by at least 63% and perhaps as high as 86% if the unfiltered cough jet distance was resolved to the anticipated maximum distance of 2-3 m. However, surgical and handmade masks, and face shields, generate significant leakage jets that may present major hazards. Conclusions: the effectiveness of the masks should mostly be considered based on the generation of secondary jets rather than on the ability to mitigate the front throughflow.

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling.

Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER-Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.

Transarticular tibiotalocalcaneal nailing versus open reduction and internal fixation for treatment of the elderly ankle fracture: protocol for a multicentre, prospective, randomised controlled trial.

INTRODUCTION: Ankle fractures are common in the elderly population. Surgical fixation is technically challenging and often results in complications due to high rates of osteoporosis and vascular disease. Open reduction and internal fixation (ORIF) often requires prolonged periods of non-weight bearing increasing the risks of complications. Tibiotalocalcaneal (TTC) nailing has been suggested as an alternative to ORIF which allows immediate weight bearing, and is suggested to result in fewer complications. This study aims to compare the two surgical techniques in the elderly population with ankle fractures. METHODS AND ANALYSIS: The study will be a multicentre, prospective, randomised controlled trial comparing ORIF to TTC nailing in 110 patients with ankle fractures aged 50 or above with a Charlson Comorbidity Index of greater than or equal to four. Participants and assessors will not be blinded to intervention. The primary outcome measure will be overall complication rate. Secondary outcomes include length of hospital stay, mobility at discharge, discharge destination, the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot score, the Olerud-Molander Ankle Score, mortality rate, rate of secondary surgical interventions and number of blood transfusions required postoperatively. Our null hypothesis is that there is no clinically significant difference in the primary outcome measure between the two treatment groups. ETHICS AND DISSEMINATION: The study has been approved by Metro South Hospital and Health Services Human Research Ethics Committee (EC00167) (reference number HREC/17/QPAH/351). DISCUSSION: Completion of this trial will provide evidence on the effectiveness of TTC nailing versus ORIF in treatment of the elderly ankle fracture. If TTC nailing is found to result in superior outcomes, this trial has the capacity to change current clinical practice. TRIAL REGISTRATION NUMBER: ACTRN12617001588381;Pre-results andU1111-1203-1704.