HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965.

Interventions for treating supracondylar elbow fractures in children.

BACKGROUND: Elbow supracondylar fractures are common, with treatment decisions based on fracture displacement. However, there remains controversy regarding the best treatments for this injury. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating supracondylar elbow fractures in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase in March 2021. We also searched trial registers and reference lists. We applied no language or publication restrictions. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials comparing different interventions for the treatment of supracondylar elbow fractures in children. We included studies investigating surgical interventions (different fixation techniques and different reduction techniques), surgical versus non-surgical treatment, traction types, methods of non-surgical intervention, and timing and location of treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data and conducted GRADE assessment for five critical outcomes: functional outcomes, treatment failure (requiring re-intervention), nerve injury, major complications (pin site infection in most studies), and cosmetic deformity (cubitus varus).  MAIN RESULTS: We included 52 trials with 3594 children who had supracondylar elbow fractures; most were Gartland 2 and 3 fractures. The mean ages of children ranged from 4.9 to 8.4 years and the majority of participants were boys. Most studies (33) were conducted in countries in South-East Asia. We identified 12 different comparisons of interventions: retrograde lateral wires versus retrograde crossed wires; lateral crossed (Dorgan) wires versus retrograde crossed wires; retrograde lateral wires versus lateral crossed (Dorgan) wires; retrograde crossed wires versus posterior intrafocal wires; retrograde lateral wires in a parallel versus divergent configuration; retrograde crossed wires using a mini-open technique or inserted percutaneously; buried versus non-buried wires; external versus internal fixation; open versus closed reduction; surgical fixation versus non-surgical immobilisation; skeletal versus skin traction; and collar and cuff versus backslab. We report here the findings of four comparisons that represent the most substantial body of evidence for the most clinically relevant comparisons.  All studies in these four comparisons had unclear risks of bias in at least one domain. We downgraded the certainty of all outcomes for serious risks of bias, for imprecision when evidence was derived from a small sample size or had a wide confidence interval (CI) that included the possibility of benefits or harms for both treatments, and when we detected the possibility of publication bias.  Retrograde lateral wires versus retrograde crossed wires (29 studies, 2068 children) There was low-certainty evidence of less nerve injury with retrograde lateral wires (RR 0.65, 95% CI 0.46 to 0.90; 28 studies, 1653 children). In a post hoc subgroup analysis, we noted a greater difference in the number of children with nerve injuries when lateral wires were compared to crossed wires inserted with a  percutaneous medial wire technique (RR 0.41, 95% CI 0.20 to 0.81, favours lateral wires; 10 studies, 552 children), but little difference when an open technique was used (RR 0.91, 95% CI 0.59 to 1.40, favours lateral wires; 11 studies, 656 children). Although we noted a statistically significant difference between these subgroups from the interaction test (P = 0.05), we could not rule out the possibility that other factors could account for this difference. We found little or no difference between the interventions in major complications, which were described as pin site infections in all studies (RR 1.08, 95% CI 0.65 to 1.79; 19 studies, 1126 children; low-certainty evidence). For functional status (1 study, 35 children), treatment failure requiring re-intervention (1 study, 60 children), and cosmetic deformity (2 studies, 95 children), there was very low-certainty evidence showing no evidence of a difference between interventions. Open reduction versus closed reduction (4 studies, 295 children) Type of reduction method may make little or no difference to nerve injuries (RR 0.30, 95% CI 0.09 to 1.01, favours open reduction; 3 studies, 163 children). However, there may be fewer major complications (pin site infections) when closed reduction is used (RR 4.15, 95% CI 1.07 to 16.20; 4 studies, 253 children). The certainty of the evidence for these outcomes is low. No studies reported functional outcome, treatment failure requiring re-intervention, or cosmetic deformity. The four studies in this comparison used direct visualisation during surgery. One additional study used a joystick technique for reduction, and we did not combine data from this study in analyses. Surgical fixation using wires versus non-surgical immobilisation using a cast (3 studies, 140 children) There was very low-certainty evidence showing little or no difference between interventions for treatment failure requiring re-intervention (1 study, 60 children), nerve injury (3 studies, 140 children), major complications (3 studies, 126 children), and cosmetic deformity (2 studies, 80 children). No studies reported functional outcome. Backslab versus sling (1 study, 50 children) No nerve injuries or major complications were experienced by children in either group; this evidence is of very low certainty. Functional outcome, treatment failure, and cosmetic deformity were not reported.  AUTHORS' CONCLUSIONS: We found insufficient evidence for many treatments of supracondylar fractures. Fixation of displaced supracondylar fractures with retrograde lateral wires compared with crossed wires provided the most substantial body of evidence in this review, and our findings indicate that there may be a lower risk of nerve injury with retrograde lateral wires. In future trials of treatments, we would encourage the adoption of a core outcome set, which includes patient-reported measures. Evaluation of the effectiveness of traction compared with surgical fixation would provide a valuable addition to this clinical field.

Are facemasks a priority for all staff in theatre to prevent surgical site infections during shortages of supply? A systematic review and meta-analysis.

BACKGROUND: The provision of facemasks must be prioritised when supplies are interrupted. These include supplies to operating rooms. The aim of this review is to evaluate the available evidence to determine the relative priority for the provision of facemasks in operating rooms to prevent surgical site infection. METHODS: A systematic search of OVID Medline, Embase & Cochrane Central was completed. Candidate full-text articles were identified and analysed by two reviewers who also assessed risk of bias. FINDINGS: Six studies were identified that described infections with and without facemask usage. The pooled effect of not wearing facemasks was a risk ratio for infection of 0.77 (0.62-0.97) in favour of not wearing masks. Only one case-controlled study evaluated facemask usage in implant surgery and demonstrated an odds ratio for developing infection of 3.34 (95% CI 1.94-5.74) if facemasks were not worn by the operating surgeon. Four studies collected microbiological cultures during periods in surgery with or without facemasks. Two demonstrated an increase in colony forming units in surgery where the wound was directly below the surgeon. One study showed equivocal results when masks were worn, and one was terminated early limiting interpretation. CONCLUSION: The use of facemasks by scrubbed staff during implant surgery should be mandatory to prevent infection. We recommend the use of facemasks by all scrubbed staff during other forms of surgery to protect the patient and staff, but the supporting evidence is weak. There is insufficient evidence to show that non-scrubbed staff must wear masks during surgery.

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study.

Background: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients. Methods: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers. Results: Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76-40.51], and with both markers plus estimated glomerular filtration rate (eGFR)- cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI. Conclusion: High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.

Genetic and gut microbiome determinants of SCFA circulating and fecal levels, postprandial responses and links to chronic and acute inflammation.

Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK, n = 2507; ZOE PREDICT-1, n = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average h2: serum = 14%(SD = 14%); stool = 12%(SD = 6%)). Furthermore, we find that gut microbiome can accurately predict their fecal levels (AUC>0.71) while presenting weaker associations with serum. Finally, we report different correlation patterns with inflammatory markers depending on the type of inflammatory response (chronic or acute trauma). Our results illustrate the breadth of the physiological relevance of SCFAs on human inflammatory and metabolic responses highlighting the need for a deeper understanding of this important class of molecules.

Interventions for treating proximal humeral fractures in adults.

BACKGROUND: Fractures of the proximal humerus are common injuries. The management, including surgical intervention, of these fractures varies widely. This is an update of a Cochrane review first published in 2001 and last updated in 2010. OBJECTIVES: To review the evidence supporting the various treatment and rehabilitation interventions for proximal humeral fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other databases, and bibliographies of trial reports. The full search ended in January 2012. SELECTION CRITERIA: All randomised controlled trials pertinent to the management of proximal humeral fractures in adults were selected. DATA COLLECTION AND ANALYSIS: Two people performed independent study selection, risk of bias assessment and data extraction. Only limited meta-analysis was performed. MAIN RESULTS: Twenty-three small randomised trials with a total of 1238 participants were included. Bias in these trials could not be ruled out. Additionally there is a need for caution in interpreting the results of these small trials, which generally do not provide sufficient evidence to conclude that any non-statistically significant finding is 'evidence of no effect'.Eight trials evaluated conservative treatment. One trial found an arm sling was generally more comfortable than a less commonly used body bandage. There was some evidence that 'immediate' physiotherapy compared with that delayed until after three weeks of immobilisation resulted in less pain and potentially better recovery in people with undisplaced or other stable fractures. Similarly, there was evidence that mobilisation at one week instead of three weeks alleviated short term pain without compromising long term outcome. Two trials provided some evidence that unsupervised patients could generally achieve a satisfactory outcome when given sufficient instruction for an adequate self-directed exercise programme.Six heterogeneous trials, involving a total of 270 participants with displaced and/or complex fractures, compared surgical versus conservative treatment. Pooled results of patient-reported functional scores at one year from three trials (153 participants) showed no statistically significant difference between the two groups (standardised mean difference -0.10, 95% CI -0.42 to 0.22; negative results favour surgery). Quality of life based on the EuroQol results scores from three trials (153 participants) showed non-statistically significant differences between the two groups at three time points up to 12 months. However, the pooled EuroQol results at two years (101 participants) from two trials run concurrently from the same centre were significantly in favour of the surgical group. There was no significant difference between the two groups in mortality (8/98 versus 5/98; RR 1.55, 95% CI 0.55 to 4.36; 4 trials). Significantly more surgical group patients had additional or secondary surgery (18/112 versus 5/111; RR 3.36, 95% CI 1.33 to 8.49; 5 trials). This is equivalent to an extra operation in one of every nine surgically treated patients.Different methods of surgical management were tested in seven small trials. One trial comparing two types of locking plate versus a locking nail for treating two-part surgical neck fractures found some evidence of better function after plate fixation but also of a higher rate of surgically-related complications. One trial comparing a locking plate versus minimally invasive fixation with distally inserted intramedullary nails found some evidence of a short-term benefit for the nailing group. Compared with hemiarthroplasty, tension-band fixation of severe injuries using wires was associated with a higher re-operation rate in one trial. Two trials found no important differences between 'polyaxial' and 'monaxial' screws combined with locking plate fixation. One trial produced some preliminary evidence that tended to support the use of medial support locking screws in locking plate fixation. One trial found better functional results for one of two types of hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial) or hemiarthroplasty (one trial). AUTHORS' CONCLUSIONS: There is insufficient evidence to inform the management of these fractures. Early physiotherapy, without immobilisation, may be sufficient for some types of undisplaced fractures. It remains unclear whether surgery, even for specific fracture types, will produce consistently better long term outcomes but it is likely to be associated with a higher risk of surgery-related complications and requirement for further surgery.There is insufficient evidence to establish what is the best method of surgical treatment, either in terms of the use of different categories of surgical intervention (such as plate versus nail fixation, or hemiarthroplasty versus tension-wire fixation) or different methods of performing an intervention in the same category (such as different methods of plate fixation). There is insufficient evidence to say when to start mobilisation after either surgical fixation or hemiarthroplasty.

Has a change in established care pathways during the first wave of the COVID-19 pandemic led to an excess death rate in the fragility fracture population? A longitudinal cohort study of 1846 patients.

OBJECTIVE: During the first wave of the COVID-19 pandemic, changes to established care pathways and discharge thresholds for patients with fragility fractures were made. This was to increase hospital bed capacity and minimise the inpatient risk of contracting COVID-19. This study aims to identify the excess death rate in this population during the first wave of the pandemic. DESIGN: A longitudinal cohort study of patients with fragility fractures identified by specific International Classification of Diseases (ICD)-10 codes. The first wave of the pandemic was defined as the 3-month period between 1 March and 1 June 2020. The control group presented between 1 March and 1 June 2019. SETTING: Two acute National Health Service hospitals within the East Midlands region of England. PARTICIPANTS: 1846 patients with fragility fractures over the aforementioned two specified matched time points. PRIMARY AND SECONDARY OUTCOME MEASURES: Four-month mortality of all patients with fragility fractures with a subanalysis of patients with fragility hip fractures. RESULTS: 832 patients with fragility fracture were admitted during the pandemic period (104 diagnosed with COVID-19). 1014 patients presented with fragility fractures in the control group. Mortality in patients with fragility fracture without COVID-19 was significantly higher among pandemic period admissions (14.7%) than the pre-pandemic cohort (10.2%) (HR=1.86; 95% CI 1.41 to 2.45; p<0.001) adjusted for age and sex. Length of stay was shorter during the pandemic period (effect size=-4.2 days; 95% CI -5.8 to -3.1, p<0.001). Subanalysis of patients with fragility hip fracture revealed a mortality of 8.4% in the pre-pandemic cohort, and 15.48% during pandemic admissions with no COVID-19 diagnosis (HR=2.08; 95% CI 1.11 to 3.90; p=0.021). CONCLUSIONS: There is a significant increase in excess death, not explained by confirmed COVID-19 infections. Altered care pathways and aggressive discharge criteria during the pandemic are likely responsible for the increase in excess deaths.

Erector Spinae Plane Blocks for the Early Analgesia of Rib Fractures in Trauma (ESPEAR): protocol for a multicentre pilot randomised controlled trial with feasibility and embedded qualitative assessment.

INTRODUCTION: Patients with rib fractures commonly experience significant acute pain and are at risk of hypoxia, retained secretions, respiratory failure and death. Effective analgesia improves these outcomes. There is widespread variation in analgesic treatments given to patients including oral, intravenous and epidural routes of administration. Erector spinae plane (ESP) blockade, a novel regional analgesic technique, may be effective, but high-quality evidence is lacking. METHODS AND ANALYSIS: To determine if a definitive trial of ESP blockade in rib fractures is possible, we are conducting a multicentre, randomised controlled pilot study with feasibility and qualitative assessment. Fifty adult patients with rib fractures will be randomised in a 1:1 ratio to ESP blockade with multimodal analgesia or placebo ESP blockade with multimodal analgesia. Participants and outcome assessors will be blinded. The primary feasibility outcomes are recruitment rate, retention rate and trial acceptability assessed by interview. ETHICS AND DISSEMINATION: The study was approved by the Oxford B Research Ethics Committee on 22 February 2022 (REC reference: 22/SC/0005). All participants will provide written consent. Trial results will be reported via peer review and to grant funders. TRIAL REGISTRATION NUMBER: ISRCTN49307616.

IgG N-glycome changes during the course of severe COVID-19: An observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. METHODS: Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). FINDINGS: Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. INTERPRETATION: The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. FUNDING: This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Trends in hospital admissions for childhood fractures in England.

Purpose: Fractures to the axial and appendicular skeleton are common in children causing loss of opportunities and disability. There are relatively few studies available to quantify the number of children who have their fractures diagnosed in the emergency department and are then admitted to hospital for ongoing management. The purpose of this study is to explore trends of frequency, types and age of children sustaining fractures who were admitted for intervention to National Health Service (NHS) hospitals. Design: The study uses data from the Hospital Episode Statistics and Office for National Statistics from 2012 to 2019 to calculate the annual incidence of hospital admission for limb, spine, facial and skull fractures per 100 000 children. Results: During 2012-2019, 368 120 children were admitted to English NHS hospitals with a fracture. 256 008 (69.5%) were upper limb fractures, 85 737 (23.3%) were lower limb fractures and 20 939 (5.7%) were skull or facial fractures. The annual incidence of upper limb fractures was highest in children aged 5-9 (348.3 per 100 000 children) and the highest incidence of lower limb fractures was in children aged 10-15 (126.5 per 100 000 children). The incidence of skull and facial fractures in preschool (age 0-4) children has been increasing at a rate of 0.629 per 100 000 children per year. Implications: The annual incidence of hospital admission for fractures in children has been shown to be consistent for several fracture types between 2012 and 2019. An increasing trend of admissions with preschool skull fractures was observed, though the study data do not have sufficient granularity to demonstrate if this is due to changes in practice or to accidental or non-accidental causes.

Development of the CORE-Kids core set of outcome domains for studies of childhood limb fractures.

AIMS: The aim of this study is to develop a core set of outcome domains that should be considered and reported in all future trials of childhood limb fractures. METHODS: A four-phase study was conducted to agree a set of core outcome domains. Identification of candidate outcome domains were identified through systematic review of trials, and outcome domains relevant to families were identified through semi-structured interviews with 20 families (parent-child pairing or group). Outcome domains were prioritized using an international three-round Delphi survey with 205 panellists and then condensed into a core outcome set through a consensus workshop with 30 stakeholders. RESULTS: The systematic review and interviews identified 85 outcome domains as relevant to professionals or families. The Delphi survey prioritized 30 upper and 29 lower limb outcome domains at first round, an additional 17 upper and 18 lower limb outcomes at second round, and four additional outcomes for upper and lower limb at the third round as important domains. At the consensus workshop, the core outcome domains were agreed as: 1) pain and discomfort; 2) return to physical and recreational activities; 3) emotional and psychosocial wellbeing; 4) complications from the injury and treatment; 5) rturn to baseline activities daily living; 6) participation in learning; 7) appearance and deformity; and 8) time to union. In addition, 9a) recovery of mobility and 9b) recovery of manual dexterity was recommended as a core outcome for lower and upper limb fractures, respectively. CONCLUSION: This set of core outcome domains is recommended as a minimum set of outcomes to be reported in all trials. It is not an exhaustive set and further work is required to identify what outcome tools should be used to measure each of these outcomes. Adoption of this outcome set will improve the consistency of research for these children that can be combined for more meaningful meta-analyses and policy development. Cite this article: Bone Joint J 2021;103-B(12):1821-1830.

Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

Longitudinal assessment of symptoms and risk of SARS-CoV-2 infection in healthcare workers across 5 hospitals to understand ethnic differences in infection risk.

BACKGROUND: : Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. We aimed to understand ethnic differences in SARS-CoV-2 seropositivity among hospital healthcare workers depending on their hospital role, socioeconomic status, Covid-19 symptoms and basic demographics. METHODS: A prospective longitudinal observational cohort study. 1364 HCWs at five UK hospitals were studied with up to 16 weeks of symptom questionnaires and antibody testing (to both nucleocapsid and spike protein) during the first UK wave in five NHS hospitals between March 20 and July 10 2020. The main outcome measures were SARS-CoV-2 infection (seropositivity at any time-point) and symptoms. Registration number: NCT04318314. FINDINGS: 272 of 1364 HCWs (mean age 40.7 years, 72% female, 74% White, ≥6 samples per participant) seroconverted, reporting predominantly mild or no symptoms. Seropositivity was lower in Intensive Therapy Unit (ITU) workers (OR=0.44 95%CI 0.24, 0.77; p=0.0035). Seropositivity was higher in Black (compared to White) participants, independent of age, sex, role and index of multiple deprivation (OR=2.61 95%CI 1.47-4.62 p=0.0009). No association was seen between White HCWs and other minority ethnic groups. INTERPRETATION: In the UK first wave, Black ethnicity (but not other ethnicities) more than doubled HCWs likelihood of seropositivity, independent of age, sex, measured socio-economic factors and hospital role.

Interventions for treating proximal humeral fractures in adults.

BACKGROUND: Proximal humeral fractures are common injuries. The management, including surgical intervention, of these fractures varies widely. OBJECTIVES: To review the evidence supporting the various treatment and rehabilitation interventions for proximal humeral fractures. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other databases, and bibliographies of trial reports. The full search ended in March 2010. SELECTION CRITERIA: All randomised controlled trials pertinent to the management of proximal humeral fractures in adults were selected. DATA COLLECTION AND ANALYSIS: Two people performed independent study selection, risk of bias assessment and data extraction. Trial heterogeneity prevented meta-analysis. MAIN RESULTS: Sixteen small randomised trials with 801 participants were included. Bias in these trials could not be ruled out.Eight trials evaluated conservative treatment. One trial found an arm sling was generally more comfortable than a less commonly used body bandage. There was some evidence that 'immediate' physiotherapy compared with that delayed until after three weeks of immobilisation resulted in less pain and potentially better recovery in people with undisplaced or other stable fractures. Similarly, there was evidence that mobilisation at one week instead of three weeks alleviated short term pain without compromising long term outcome. Two trials provided some evidence that unsupervised patients could generally achieve a satisfactory outcome when given sufficient instruction for an adequate physiotherapy programme.Surgery improved fracture alignment in two trials but was associated with more complications in one trial, and did not result in improved shoulder function. Preliminary data from another trial showed no significant difference in complications, quality of life or costs between plate fixation and conservative treatment. In one trial, hemiarthroplasty resulted in better short-term function with less pain and disability when compared with conservative treatment for severe injuries.Compared with hemiarthroplasty, tension-band fixation of severe injuries using wires was associated with a high re-operation rate in one trial. One trial found better functional results for one type of hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial) or hemiarthroplasty (one trial). AUTHORS' CONCLUSIONS: There is insufficient evidence to inform the management of these fractures. Early physiotherapy, without immobilisation, may be sufficient for some types of undisplaced fractures. It is unclear whether surgery, even for specific fracture types, will produce consistently better long term outcomes.

Outcomes reported in trials of childhood fractures: a systematic review.

AIMS: To analyze outcomes reported in trials of childhood fractures. METHODS: OVID MEDLINE, Embase, and Cochrane CENTRAL databases were searched on the eighth August 2019. A manual search of trial registries, bibliographic review and internet search was used to identify additional studies. 11,476 studies were screened following PRISMA guidelines. 100 trials were included in the analysis. Data extraction was completed by two researchers for each trial. Study quality was not evaluated. Outcomes reported by trials were mapped onto domains in the World Health Organization (WHO) International Classification of Function framework. RESULTS: In all, 525 outcomes were identified representing 52 WHO domains. Four domains were reported in more than 50% of trials: structure of upper/lower limb, sensation of pain, mobility of joint function, and health services, systems and policies. The Activities Scale for Kids performance (ASK-p) score was the most common outcome score reported in 6/72 upper limb and 4/28 lower limb trials. CONCLUSION: There is a diverse range of outcomes reported in trials of childhood fractures covering all areas in the International Classification of Functioning, Disability and Health (ICF) framework. There were three common upper limb and three common lower limb outcomes. In the absence of a core outcome set, we recommend that upper limb trials report pain, range of movement and radiograph appearance of the arm and lower limb trials report pain, radiograph appearance of the leg and healthcare costs to improve consistency of reporting in future trials.Cite this article: Bone Joint Open 2020;1-5:167-174.

High mortality following revision hip arthroplasty for periprosthetic femoral fracture.

AIMS: To determine mortality risk after first revision total hip arthroplasty (THA) for periprosthetic femoral fracture (PFF), and to compare this to mortality risk after primary and first revision THA for other common indications. METHODS: The study cohort consisted of THAs recorded in the National Joint Registry between 2003 and 2015, linked to national mortality data. First revision THAs for PFF, infection, dislocation, and aseptic loosening were identified. We used a flexible parametric model to estimate the cumulative incidence function of death at 90 days, one year, and five years following first revision THA and primary THA, in the presence of further revision as a competing risk. Analysis covariates were age, sex, and American Society of Anesthesiologists (ASA) grade. RESULTS: A total of 675,078 primary and 74,223 first revision THAs were included (of which 6,131 were performed for PFF). Following revision for PFF, mortality ranged from 9% at 90 days, 21% at one year, and 60% at five years in the highest risk group (males, ≥ 75 years, ASA ≥ 3) to 0.6%, 1.4%, and 5.5%, respectively, for the lowest risk group (females, < 75 years, ASA ≤ 2). Mortality was greater in all groups following first revision THA for PFF than for primary THA. Compared to mortality risk after first revision THA for infection, dislocation, or aseptic loosening, revision for PFF was associated with higher five-year mortality in all groups except males < 75 years with an ASA ≤ 2. CONCLUSION: Mortality risk after revision THA for PFF is high, reaching 60% at five years in the highest risk patient group. In comparison to other common indications for revision, PFF demonstrated the highest overall risk of mortality at five years. These estimates can be used in the surgical decision-making process and when counselling patients and carers regarding surgical risk. Cite this article: Bone Joint J 2020;102-B(12):1670-1674.

Quality of patient-reported outcomes used for quality of life, physical function, and functional capacity in trials of childhood fractures.

AIMS: This study evaluates the quality of patient-reported outcome measures (PROMs) reported in childhood fracture trials and recommends outcome measures to assess and report physical function, functional capacity, and quality of life using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) standards. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review of OVID Medline, Embase, and Cochrane CENTRAL was performed to identify all PROMs reported in trials. A search of OVID Medline, Embase, and PsycINFO was performed to identify all PROMs with validation studies in childhood fractures. Development studies were identified through hand-searching. Data extraction was undertaken by two reviewers. Study quality and risk of bias was evaluated by COSMIN guidelines and recorded on standardized checklists. RESULTS: Searches yielded 13,672 studies, which were screened to identify 124 trials and two validation studies. Review of the 124 trials identified 16 reported PROMs, of which two had validation studies. The development papers were retrieved for all PROMs. The quality of the original development studies was adequate for Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility and Upper Extremity and doubtful for the EuroQol Five Dimension Youth questionnaire (EQ-5D-Y). All other PROMs were found to have inadequate development studies. No content validity studies were identified. Reviewer-rated content validity was acceptable for six PROMs: Activity Scale for Kids (ASK), Childhood Health Assessment Questionnaire, PROMIS Upper Extremity, PROMIS Mobility, EQ-5D-Y, and Pediatric Quality of Life Inventory (PedsQL4.0). The Modified Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was shown to have indeterminate reliability and convergence validity in one study and PROMIS Upper Extremity had insufficient convergence validity in one study. CONCLUSION: There is insufficient evidence to recommend strongly the use of any single PROM to assess and report physical function or quality of life following childhood fractures. There is a need to conduct validation studies for PROMs. In the absence of these studies, we cautiously recommend the use of the PROMIS or ASK-P for physical function and the PedsQL4.0 or EQ-5D-Y for quality of life. Cite this article: Bone Joint J 2020;102-B(12):1599-1607.

CORE-Kids: a protocol for the development of a core outcome set for childhood fractures.

INTRODUCTION: Limb fractures in children are common yet there are few trials that compare treatments for these injuries. There is significant heterogeneity in the outcomes reported in the paediatric orthopaedic literature, which limits the ability to compare study results and draw firm conclusions. The aim of the CORE-Kids Study is to develop a core outcome set for use in research studies of childhood limb fractures. A core outcome set will provide a minimum set of outcomes to be measured in all trials to minimise the heterogeneity of outcomes reported and minimise reporting bias. A core outcome set ensures that outcomes are reported that are relevant to families as well as clinicians. The core outcome set will include additional upper and lower limb modules. METHODS: The development of the core outcome set will require four phases to evaluate:What are the outcomes that are relevant to professionals?What are the outcomes that are relevant to families?What are the most important of these outcomes?Which outcomes should be included in the core outcome set?This will be completed through a systematic review of trials to identify the outcomes domains that are relevant to trialists. A series of semi-structured interviews will be completed with families to identify the outcome domains that are relevant to families. These outcome domains will be used in a three-round Delphi Study to analyse the importance of these outcome domains to a range of stakeholders including parents, clinicians and researchers. Following this, the core outcome set will be decided at a consensus meeting. ETHICS AND DISSEMINATION: Ethical approval has been awarded HRA/REC IRAS number 262503. Date of approval 06/08/2019. Dissemination will be through scientific literature and international societies. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials Initiative, registration number: 1274. Date of registration 13/12/2018. PROSPERO REGISTRATION NUMBER: CRD42018106605.

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Evaluating the cervical spine in confused or unconscious adults after blunt trauma.

Potential injury to the cervical spine should be considered in all patients who have suffered blunt trauma. Early spinal immobilization is required to minimize the risk of secondary spinal cord injury. However, prolonged immobilization is associated with its own morbidity. Clinical evaluation of the cervical spine in confused or unconscious adult trauma patients is challenging, and imaging is required to safely 'clear' the cervical spine. Despite the existence of national guidelines, significant variations in practice exist. This article summarizes the evidence for the initial stabilization of the cervical spine in adult trauma patients. It reviews the imaging modalities available and the criteria for discontinuation of cervical spine immobilization.