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With reports of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) continuing to increase and therapeutic options decrease, infection control methods are of increasing importance. Here we investigate the relationship between surveillance and infection control. Surveillance plays two roles with respect to control: it allows detection of infected/colonized individuals necessary for their removal from the general population, and it allows quantification of control success. We develop a stochastic model of MRSA transmission dynamics exploring the effects of two screening strategies in an epidemic setting: random and on admission. We consider both hospital and community populations and include control and surveillance in a single framework. Random screening was more efficient at hospital surveillance and allowed nosocomial control, which also prevented epidemic behaviour in the community. Therefore, random screening was the more effective control strategy for both the hospital and community populations in this setting. Surveillance strategies have significant impact on both ascertainment of infection prevalence and its control. [ABSTRACT FROM AUTHOR]

Accreditation of healthcare services provides quality assurance of hospital practice to support safe and effective care for patients. Accreditation programmes focused on antimicrobial stewardship (AMS) have been developed in high-income countries (HIC) and recently the WHO has developed a toolkit to support AMS practice in low and middle-income (LMIC) countries. BSAC has developed their Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS) for hospitals based on globally applicable standards. GAMSAS aims to support healthcare organizations to build measurable AMS programmes and to support spread of best practice. GAMSAS involves a desktop assessment by BSAC experts followed by a hospital visit to gather further insight into how a hospital's AMS programme operates. A final report of compliance with the GAMSAS standards and a recommendation about accreditation at one of three levels is formally approved at a GAMSAS panel meeting involving well-established global experts in AMS. The BSAC GAMSAS team reflect on progress during the first year and ambitions for future spread., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort., Methods: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples., Results: Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77)., Interpretation: In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables., Competing Interests: Competing interests: MPW, WH and TB have received speaker fees from Gilead Sciences. JY has received honoraria from Pfizer for contributing to a CAPA working group. TB has received Advisory Board fees from Gilead Sciences and Mundipharma and funding from MSD and Pfizer. DRJ is the president of the British Society for Antimicrobial Chemotherapy and has received honoraria from Pfizer, Shionogi, Menarini and Tillots. SS has received honoraria from Pfizer and Gilead for educational purposes. PLW performed diagnostic evaluations and received meeting sponsorship from Associates of Cape Cod, Bruker, Dynamiker and Launch Diagnostics; speaker fees, expert advice fees and meeting sponsorship from Gilead; and speaker and expert advice fees from Pfizer and expert advice fees from F2G., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tibial post failure is a rare but serious complication of posterior-stabilized total knee arthroplasty that requires revision surgery. Although tibial post fracture has previously been reported, this case involves an implant with a design feature that may predispose patients to the complication. The fracture also occurred later than observed in most other reports. A 72-year-old male who had undergone a posterior stabilized total knee arthroplasty seven years prior presented with knee pain and instability after a fall from standing. Although plain radiographs were not diagnostic, history and physical exam suggested failure of the tibial polyethylene post. This was confirmed during surgery when the fractured component was identified in the suprapatellar pouch. Given absence of malrotation or malalignment of the well-fixed femoral and tibial components, a polyethylene liner exchange was performed. Postoperatively, the patient had complete resolution of pain and instability with 0-120 degrees of stable ROM, which has persisted to latest follow-up at 6 months.

Objectives: Outbreaks of infection related to flexible endoscopes are well described. However, flexible endoscopy also requires the use of ancillary equipment such as irrigation plugs. These are potential vectors of infection but are infrequently highlighted in the literature. This paper reports a cystoscopy-associated outbreak of Pseudomonas aeruginosa from contaminated irrigation plugs in a UK tertiary care centre., Methods: Laboratory, clinical and decontamination unit records were reviewed, and audits of the decontamination unit were performed. Flexible cystoscopes and irrigation plugs were assessed for contamination. Retrospective and prospective case finding was performed utilizing the microbiology laboratory information management system. Available P. aeruginosa isolates underwent variable nucleotide tandem repeat (VNTR) typing. Confirmed cases were defined as P. aeruginosa infection with an identical VNTR profile to an outbreak strain., Results: Three strains of P. aeruginosa were isolated from five irrigation plugs but none of the flexible cystoscopes. No acquired resistance mechanisms were detected. Fifteen confirmed infections occurred, including bacteraemia, septic arthritis and urinary tract infection. While failure of decontamination likely occurred because the plugs were not dismantled prior to reprocessing, the manufacturer's reprocessing instructions were also incompatible with standard UK practice. The Medicines and Healthcare Products Regulatory Agency was informed. A field safety notice was issued, and the manufacturer issued updated reprocessing instructions., Conclusions: Ancillary equipment can represent an important vector for infection, and should be considered during outbreak investigations. Users should review the manufacturer's instructions for reprocessing ancillary equipment to ensure that they are compatible with available procedures., (Copyright © 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The relationship between operative times and patient outcomes in total hip arthroplasty (THA) has not been well defined., Methods: From January 2016 to December 2019, data were prospectively collected for THA patients in the FORCE-TJR registry and hospital EMR of an academic total-joint center., Results: 1,123 patients were included. Operative times ranged from 36 to 366 minutes, with a mean operative time of 111.26+/-31.37 minutes. Unadjusted GLM showed HOOS pain, ADL, and QoL scores differed across operative times, with patients who had operative times between 106 and 120 minutes having significantly lower pain, higher function, and better quality of life at 12 months, especially compared to patients with operative times < 90 minutes. Patients who had operative times between 106 and 120 minutes had significantly better VR-12 PCS and MCS at 12 months. Although statistically significant, differences were small and did not persist after controlling for within-surgeon effects, patient socio-demographics and baseline patient-reported outcomes, suggesting that patient characteristics or within-surgeon effects may play a more significant role in these patient-reported outcomes than operative time., Conclusion: This study showed that among THA patients, operative times were significantly associated with patient-reported outcomes at 12 months post-operatively, but is one of many surgeon and patient-related factors with effect on THA outcome.

Case: A 79-year-old active male presented during the first COVID-19 pandemic surgery moratorium with late Staphylococcus lugdunensis periprosthetic total hip arthroplasty infection. Due to the unprecedented circumstances, novel treatment of IV and oral antibiotic suppression was trialed without preceding surgical intervention. At latest follow-up, the patient has two-year revision-free survival with normalization of inflammatory markers and MRI findings, and resolution of clinical symptoms., Conclusion: We report a novel surgery-sparing treatment for periprosthetic hip infection. Judicious caution should be used in the application of similar therapies, as host and organism characteristics likely contributed substantially to the success of this case.

Elderly trauma victims whose care is shared between surgeons and physicians have improved clinical outcomes and shorter hospital lengths of stay (LOS). To test whether a similar benefit can be gained for patients suffering traumatic brain injury (TBI), a quality improvement project (QIP) was run in which a neurologist was enrolled into the pre-existing neurotrauma team. Mortality rates, LOS and rates of readmission within 30 days of discharge were compared between two cohorts of TBI patients: 80 admittedly prior to the QIP and 80 admitted during the QIP. The two cohorts were well matched for age, gender, mechanism of injury, Glasgow coma score and types of injury. The QIP was not associated with a reduction in mortality but was associated with a significant reduction in mean LOS (from 25.7 days to 17.5 days; p=0.04) and a reduction in readmissions (from seven to zero patients; p=0.01)., (© Royal College of Physicians 2022. All rights reserved.)

Background: Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff., Methods: We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity., Results: A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07-1.49 and Black: 2.42; 1.90-3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27-0.61)., Conclusions: Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Leicester was the first city in the UK to have 'local lockdown' measures imposed in response to high community rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. As part of this response, a directive was issued by NHS England to offer testing of asymptomatic healthcare workers (HCWs) at University Hospitals of Leicester NHS Trust (UHL) for SARS-CoV-2 infection., Methods: Between 20 July and 14 August 2020, we invited all HCWs at UHL to attend for SARS-CoV-2 testing by nucleic acid amplification (NAAT). We combined the result of this assay with demographic information from the electronic staff record., Results: A total of 1150 staff (~8% of the workforce) volunteered. The median age was 46 years (IQR 34-55), 972 (84.5%) were female; 234 (20.4%) were of South Asian and 58 (5.0%) of Black ethnicity; 564 (49.0%) were nurses/healthcare assistants. We found no cases of asymptomatic infection. In comparison, average community test positivity rate in Leicester city was 2.6%., Conclusions: Within the context of local lockdowns due to high community transmission rates, voluntary testing of asymptomatic staff has low uptake and low yield and thus its premise and cost-effectiveness should be re-considered., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Klebsiella pneumoniae is an important pathogenic bacterium commonly associated with human healthcare and community-acquired infections. In recent years, K. pneumoniae has become a significant threat to global public and veterinary health, because of its high rates of antimicrobial resistance (AMR). Early diagnosis of K. pneumoniae infection and detection of any associated AMR would help to accelerate directed therapy and reduce the risk of the emergence of multidrug-resistant isolates. In this study, we identified three target genes ( yhaI , epsL , and xcpW ) common to K. pneumoniae isolates from both China and Europe and designed loop-mediated isothermal amplification (LAMP) assays for the detection of K. pneumoniae in clinical samples. We also designed LAMP assays for the detection of five AMR genes commonly associated with K. pneumoniae . The LAMP assays were validated on a total of 319 type reference strains and clinical isolates of diverse genetic backgrounds, in addition to 40 clinical human sputum samples, and were shown to be reliable, highly specific, and sensitive. For the K. pneumoniae -specific LAMP assay, the calculated sensitivity, specificity, and positive and negative predictive values (comparison with culture and matrix-assisted laser desorption/ionization-time of flight mass spectrometry) were all 100% on clinical isolates and, respectively, of 100%, 91%, and 90%, and 100% when tested on clinical sputum samples, while being significantly faster than the reference methods. For the bla KPC and other carbapenemases' LAMP assays, the concordance between the LAMP results and the references methods (susceptibility tests) was 100%, on both pure cultures ( n = 125) and clinical samples ( n = 18). In conclusion, we developed highly sensitive and specific LAMP assays for the clinical identification of K. pneumoniae and detection of carbapenem resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poirier, Kuang, Siedler, Borah, Mehat, Liu, Tai, Wang, van Vliet, Ma, Jenkins, Clark, La Ragione, Qu and McFadden.)

Background/aims: Data concerning differences in demographics/disease severity between the first and second waves of COVID-19 are limited. We aimed to examine prognosis in patients presenting to hospital with COVID-19 amongst different ethnic groups between the first and second waves in the UK., Methods: In this retrospective cohort study, we included 1763 patients presenting to a regional hospital centre in Leicester (UK) and compared those in the first ( n  = 956) and second ( n  = 807) waves. Admission National Early Warning Scores, mechanical ventilation and mortality rate were lower in the second wave compared with the first., Results: Thirty-day mortality risk in second wave patients was approximately half that of first wave patients [adjusted hazard ratio (aHR) 0.55, 95% confidence interval (CI) 0.40-0.75]. In the second wave, Black patients were at higher risk of 30-day mortality than White patients (4.73, 1.56-14.3)., Conclusion: We found that disporportionately higher risks of death in patients from ethnic minority groups were not equivalent across consecutive waves of the pandemic. This suggests that risk factors for death in those from ethnic minority groups are malleable and potentially reversible. Our findings need urgent investigation in larger studies., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: KK is the Director of the University of Leicester Centre for Black Minority Ethnic Health, Trustee of the South Asian Health Foundation and Chair of the Ethnicity Subgroup of SAGE. MP reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work., (© The Author(s), 2022.)

Background: Healthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce., Methods and Findings: We conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26-0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62-0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction., Conclusions: Ethnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MP reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work. KK is a member of Independent SAGE and the ethnicity subgroup of SAGE and national lead for ethnicity and diversity for National Institute for Health Applied Research Collaborations and Director for University of Leicester Centre for Black Minority Ethnic Health.

Objectives: Surveillance studies for Staphylococcus aureus carriage are a primary tool to survey the prevalence of methicillin-resistant S. aureus (MRSA) in the general population, patients and healthcare workers. We have previously reported S. aureus carriage in various African countries, including Cape Verde., Methods: Whole-genome sequences of 106 S. aureus isolates from Cape Verde were determined., Results: Staphylococcus aureus carriage isolates in Cape Verde show high genetic variability, with the detection of 27 sequence types (STs) and three primary genetic clusters associated with ST152, ST15 and ST5. One transmission event with less than eight core-genome single nucleotide polymorphisms (cgSNP) differences was detected among the ST5-VI MRSA lineage. Genetic analysis confirmed the phenotypic resistance and allowed the identification of six independent events of plasmid or transposon loss associated with the deletion of blaZ in nine isolates. In the four ST5 MRSA isolates, loss of the blaZ plasmid coincided with the acquisition of SCCmec type VI and an unusual penicillin phenotype with a minimum inhibitory concentration (MIC) at the breakpoint, indicating an adaptation trend in this endemic lineage. Similar events of blaZ plasmid loss, with concomitant acquisition SCCmec elements, were detected among ST5 isolates from different geographical origins., Conclusion: Overall, the genome data allowed to place isolates in a phylogenetic context and to identify different blaZ gene deletions associated with plasmid or transposon loss. Genomic analysis unveiled adaptation and evolution trends, namely among emerging MRSA lineages in the country, which deserve additional consideration in the design of future infection control protocols., Competing Interests: Competing interests None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The 2019 update to the US consensus guideline for vancomycin therapeutic monitoring advocates using Bayesian-guided personalised dosing to maximise efficacy and minimise toxicity of vancomycin. We conducted an observational cohort study of the implementation of bed-side Bayesian-guided vancomycin dosing in vascular surgery patients., Methods: Over a 9-month prospective study period, vascular surgery patients were dosed vancomycin using Bayesian-guided dosing decision tool (DoseMeRx) and compared retrospectively with a control group admitted to the same ward in the 14 months prior to the study and dosed using a standard algorithmic approach. Primary endpoints were proportion of patients achieving mean area under the curve in 24 hours (AUC 24 ) in the acceptable range 350-450 mg/L• h and percentage time in acceptable range (%TTR). Secondary endpoints focused on clinical outcomes including incidence of acute kidney injury., Results: A significantly higher proportion of DoseMeRx patients achieved mean AUC 24 values in the acceptable range compared to the control group; 71/104 (68.3%) vs 58/139 (41.7%), P < .005. The median %TTR was also greater in DoseMeRx patients compared to the control group (57.1 vs 30.0%, P < .00001). Patients in the DoseMeRx group missed an average of 0.23 doses per course compared to 1.04 doses in the control group (P < .00001). No difference was observed in secondary (clinical) outcomes between the 2 groups., Conclusion: Bedside Bayesian-guided personalised dosing of vancomycin increases the proportion of patients achieving target AUC 24 and the %TTR., (© 2020 The British Pharmacological Society.)

Antimicrobial stewardship programs focus on reducing overuse of broad-spectrum antibiotics (BSAs), primarily through interventions to change prescribing behavior. This study aims to identify multi-level influences on BSA overuse across diverse high and low income, and public and private, healthcare contexts. Semi-structured interviews were conducted with 46 prescribers from hospitals in the UK, Sri Lanka, and South Africa, including public and private providers. Interviews explored decision making about prescribing BSAs, drivers of the use of BSAs, and benefits of BSAs to various stakeholders, and were analyzed using a constant comparative approach. Analysis identified drivers of BSA overuse at the individual, social and structural levels. Structural drivers of overuse varied significantly across contexts and included: system-level factors generating tensions with stewardship goals; limited material resources within hospitals; and patient poverty, lack of infrastructure and resources in local communities. Antimicrobial stewardship needs to encompass efforts to reduce the reliance on BSAs as a solution to context-specific structural conditions.

Objectives: Data on baseline drug resistance important in informing future antimicrobial stewardship programs. So far, no data on the antimicrobial drug resistance of clinical isolates available for the African archipelago of Cabo Verde., Methods: We performed a retrospective analysis over years (2013-17) of the drug susceptibility profiles of clinical isolates in the two main hospitals of Cabo Verde. For Escherichia coli and Staphylococcus aureus, representing 47% and 26% of all clinical isolates, the antimicrobial drug resistance profile was reported for six representative drugs., Results: For E. coli we detected an increase in resistance to ampicillin, amoxicillin/clavulanic acid, ceftriaxone, ciprofloxacin and trimethoprim-and for S. aureus to methicillin, erythromycin and trimethoprim-sulfamethoxazole. This increase in both the most commonly isolated bacterial pathogens is alarm as it might compromise empirical treatment in a setting with limited access to laboratory testing., Conclusions: When compared to the published low resistance rates in carriage isolates, the more alarming situation in clinical isolates for S. aureus might encourage antimicrobial stewardship programs to reduce in hospital settings, possibly as part of the Cabo Verdean national plan against antimicrobial drug resistance., Competing Interests: Declaration of Competing Interest Authors declare no competing interest with respect to the work performed in the manuscript., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2., Methods: We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown., Findings: 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p <0.001 for all ethnic minority groups vs White). After adjustment, compared to White ethnicity, South Asian (aOR 2.44 95%CI 2.01, 2.97), Black (aOR 2.56 95%CI 1.71, 3.84) and Other (aOR 2.53 95%CI 1.74, 3.70) ethnicities were more likely to test positive, as were those with a larger estimated household size (aOR 1.06 95%CI 1.02, 1.11). We saw increasing proportions of positive tests in the three weeks post-lockdown amongst the ethnic minority , but not the White, cohort. Estimated household size was associated with PCR positivity after, but not before, lockdown (aOR 1.10 95%CI 1.03, 1.16)., Interpretation: In individuals presenting with suspected COVID-19, those from ethnic minority communities and larger households had an increased likelihood of SARS-CoV-2 PCR positivity. Pandemic control measures may have more rapid impact on slowing viral transmission amongst those of White ethnicity compared to ethnic minority groups, Research is urgently required to understand the mechanisms underlying these disparities and whether public health interventions have differential effects on individuals from ethnic minority groups., Funding: 10.13039/100006662 NIHR., Competing Interests: Dr. Minhas reports grants from National Institute for Health Research (NIHR), during the conduct of the study; Dr. Tang reports personal fees from Abbvie UK Ltd, outside the submitted work; Professor Davies reports grants from NIHR BRC, during the conduct of the study; Dr. Pareek reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work., (© 2020 The Author(s).)

OXA-48 producers can be difficult to detect in clinical specimens due to phenotypic low-level resistance to carbapenems. Additionally, low infection rates make clinical specimens poor sentinels for the presence of OXA-48 producers within a healthcare institution. We report an outbreak of OXA-48-producing Klebsiella pneumoniae (OXAKp) that was discovered following culture of OXAKp in a urine specimen from a patient with no known risk factors for acquisition. Widespread screening across medical wards in the trust revealed evidence of transmission across several wards. Samples from 60 patients were positive for OXAKp. Five patients had OXAKp clinical infection, four of whom were treated with ceftazidime/avibactam. Variable number tandem repeat analysis of the OXAKp isolates revealed two predominant strain types clustered around two groups of wards. Infection prevention measures included isolation and cohort nursing of infected and colonized patients, restriction of affected ward areas to new admissions, stringent hand hygiene and use of personal protective equipment. Environmental cleaning of patient areas was carried out using chlorine-releasing disinfectants and hydrogen peroxide vapour. Entire wards were decanted to enable effective cleaning of empty ward areas. The outbreak lasted almost five months and is estimated to have cost around £400 000. During the course of the outbreak, there were five reported prescription and administration incidents related to confusion between ceftazidime and ceftazidime/avibactam. No patient harm resulted from these incidents and the implementation of brand name prescribing for ceftazidime/avibactam prevented further incidents., (© 2019 The Authors.)

Overuse of broad-spectrum antibiotics in secondary care is a key contributor to the emergence and spread of antimicrobial resistance (AMR); efforts are focused on minimizing antibiotic overuse as a crucial step toward containing the global threat of AMR. The concept of overtreatment has, however, been difficult to define. Efforts to address the overuse of medicine need to be informed by an understanding of how prescribers themselves understand the problem. We report findings from a qualitative interview study of 46 acute care hospital prescribers differing in seniority from three countries: United Kingdom, Sri Lanka and South Africa. Prescribers were asked about their understanding of inappropriate use of antibiotics. Prescriber definitions of inappropriate use included relatively clear-cut and unambiguous cases of antibiotics being used "incorrectly" (e.g., in the case of viral infections). In many cases, however, antibiotic prescribing decisions were seen as involving uncertainty, with prescribers having to make decisions about the threshold for appropriate use. Decisions about thresholds were commonly framed in moral terms. Some prescribers drew on arguments about their duty to protect public health through having a high threshold for prescribing, while others made strong arguments for prioritizing risk avoidance for the patients in front of them, even at a cost of increased resistance. Notions of whether prescribing was inappropriate were also contextually dependent: high levels of antibiotic prescribing could be seen as a rational response when prescribers were working in challenging contexts, and could be justified in relation to financial and social considerations. Inappropriate antibiotic use is framed by prescribers not just in clinical, but also in moral and contextual terms; this has implications for the design and implementation of antibiotic stewardship interventions aiming to reduce inappropriate use of antibiotics globally., (Copyright © 2020 Tarrant, Krockow, Nakkawita, Bolscher, Colman, Chattoe-Brown, Perera, Mehtar and Jenkins.)

Introduction: Despite the proven success of anterior cervical surgery (ACS) postoperative issues can arise, with retropharyngeal hematoma (RH) being one of the most feared. A recent USA Today article highlighted the failed management and subsequent death of patients developing RH after ACS. The article calls into question the safety of performing ACS in an outpatient setting., Methods: We tested the knowledge of 20 healthcare professionals (4 surgeons, 16 ancillary providers) regarding ways to minimize the post-ACS complications. We used a multiple-choice and fill-in-the-blank test. We then developed a No S.C.A.R.E. safety protocol and after teaching the same professionals, re-administered the examination to assess improvement., Results: We identified large gaps in knowledge between spine surgeons and other providers (92.3% versus 31.2%) on preintervention testing. Postintervention testing showed significant improvement in nonsurgeon scores (31.2% to 86.1%, P < 0.01). Improvement was also seen in provider confidence after completion of the education module., Conclusion: Previous studies demonstrate that the incidence of RH necessitating evacuation after ACS is extremely small (<1%). For rare complications, healthcare teams may benefit from educational modules and standardized protocols. After implementation of our No S.C.A.R.E. protocol, provider knowledge and confidence markedly improved. We recommend similar education modules and protocols be used at other institutions performing ACS.

Background: Antimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way., Objectives: We aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma., Sources: We conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas., Content: The social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms., Implications: We conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance is a global health threat, partly driven by inappropriate antibiotic prescriptions for acute medical patients in hospitals., Aim: To provide a systematic review of qualitative research on antibiotic prescribing decisions in hospitals worldwide, including broad-spectrum antibiotic use., Methods: A systematic search of qualitative research on antibiotic prescribing for adult hospital patients published between 2007 and 2017 was conducted. Drawing on the Health Belief Model, a framework synthesis was conducted to assess threat perceptions associated with antimicrobial resistance, and perceived benefits and barriers associated with antibiotic stewardship., Findings: The risk of antimicrobial resistance was generally perceived to be serious, but the abstract and long-term nature of its consequences led physicians to doubt personal susceptibility. While prescribers believed in the benefits of optimizing prescribing, the direct link between over-prescribing and antimicrobial resistance was questioned, and prescribers' behaviour change was frequently considered futile when fighting the complex problem of antimicrobial resistance. The salience of individual patient risks was a key barrier to more conservative prescribing. Physicians perceived broad-spectrum antibiotics to be effective and low risk; prescribing broad-spectrum antibiotics involved low cognitive demand and enabled physicians to manage patient expectations. Antibiotic prescribing decisions in low-income countries were shaped by a context of heightened uncertainty and risk due to poor microbiology and infection control services., Conclusions: When tackling antimicrobial resistance, the tensions between immediate individual risks and long-term collective risks need to be taken into account. Efforts to reduce diagnostic uncertainty and to change risk perceptions will be critical in shifting practice., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Modular junctions have been associated with corrosion in total hip arthroplasty. In a small number of cases, disassociation of the femoral head from the stem following gross wear of the taper has been reported. The purpose of this study was to investigate the role of corrosion in the development of mechanical changes leading to disassociation. Twenty-one retrieved stems and heads of one design previously reported with head disassociation were identified in an IRB-approved database. Components were scored for corrosion and measured for material loss. Stem alloy hardness was measured. Parametric and non-parametric statistics were performed (α < 0.05). Seven of twenty-one stems demonstrated gross material loss of the stem taper and head disassociation. The maximum linear depth (MLD) of material loss on stem tapers without dissociation and all head bores was 7.63 ± 6.04 and 63.76 ± 60.83 μm, respectively. Hardness of the stem material was statistically distinct, but similar to other stem materials. Results suggest material loss via corrosion at the head bore loosens the taper lock, allowing relative motion leading to abrasive wear of the stem taper. All cases of disassociation occurred at greater than 65 months with a minimum of 50 μm of loss at on the head bore. It may be warranted to survey patients with systems reporting head disassociation; for this system, including recalled heads, risk appears to begin after 6 years in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2996-3003, 2018., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Traumatic brain injury (TBI) is a leading cause of death and disability, particularly among the young. Despite this, no disease-specific treatments exist. Recently, blood-brain barrier disruption and parenchymal fibrinogen deposition have been reported in acute traumatic brain injury and in long-term survival; however, their contribution to the neuropathology of TBI remains unknown. The presence of fibrinogen-a well-documented activator of microglia/macrophages-may be associated with neuroinflammation, and neuronal/axonal injury. To test this hypothesis, cases of human TBI with survival times ranging from 12 h to 13 years (survival <2 months, n = 15; survival >1 year, n = 6) were compared with uninjured controls (n = 15). Tissue was selected from the frontal lobe, temporal lobe, corpus callosum, cingulate gyrus, and brainstem, and the extent of plasma protein (fibrinogen and immunoglobulin G [IgG]) deposition, microglial/macrophage activation (CD68 and ionized calcium-binding adapter molecule 1 [Iba-1] immunoreactivity), neuronal density, and axonal transport impairment (β-amyloid precursor protein [βAPP] immunoreactivity) were assessed. Quantitative analysis revealed a significant increase in parenchymal fibrinogen and IgG deposition following acute TBI compared with long-term survival and control. Fibrinogen, but not IgG, was associated with microglial/macrophage activation and a significant reduction in neuronal density. Perivascular fibrinogen deposition also was associated with microglial/macrophage clustering and accrual of βAPP in axonal spheroids, albeit rarely. These findings mandate the future exploration of causal relationships between fibrinogen deposition, microglia/macrophage activation, and potential neuronal loss in acute TBI.

Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions. To this end, experiments were carried out to analyse and correlate post-injury oxidative stress distribution with cognitive deficits on a live rat exposed to blast. A computational model of the rat head was developed from imaging data and validated against in vivo brain displacement measurements. The blast event was reconstructed in silico to provide mechanistic thresholds that best correlate with cognitive damage at the regional neuronal tissue level, irrespectively of the shape or size of the brain tissue types. This approach was leveraged on a human head model where the prediction of cognitive deficits was shown to correlate with literature findings. The mechanistic insights from this work were finally used to propose a novel protective device design roadmap and potential avenues for therapeutic innovations against blast traumatic brain injury.

Introduction: The goal of this study was to examine patterns in the likelihood of consent to genetic research among participants in a prospective kidney disease cohort and biobank, and to determine demographic, clinical, and socioeconomic factors linked to consent for ongoing and future genetic research., Methods: The Clinical Phenotyping Resource and Biobank Core (C-PROBE) enrolled 1628 adult and pediatric patients with chronic kidney disease from 2009 to 2017 across 7 sites in the United States. Participants were asked at annual study visits for consent to provide DNA samples for future genetic studies. We compared characteristics of participants by initial consent outcome and consent status at their most recent study visit., Results: Of the C-PROBE participants, 96% consented to genetic studies at their initial study visit. Although African Americans were slightly less likely to consent at baseline (93% vs. 97%, odds ratio = 0.3, P  < 0.02), there were no significant racial or ethnic differences with longitudinal participation. Also, pediatric and adult genetic consent rates were equivalent. The major persistent differences in the likelihood of consent were based on enrollment site, which ranged from 85% to 100% ( P  < 0.0001)., Conclusion: Overall, genetic consent rates for kidney research within the C-PROBE cohort were high. However, differences in consent rates over time and by recruitment site highlight the complexity of genetic consent for biobanking, and potential limitations for generalizability of observations.