Investigation of healthcare-associated SARS-CoV-2 infection: Learning outcomes from an investigative process in the initial phase of the pandemic.

Background: Healthcare-associated (HCA) SARS-CoV-2 infection is a significant contributor to the spread of the 2020 pandemic. Timely review of HCA cases is essential to identify learning to inform infection prevention and control (IPC) policies and organisational response. Aim: To identify key areas for improvement through rapid investigation of HCA SARS-CoV-2 cases and to implement change. Methods: Cases were identified based on date of first positive SARS-CoV-2 PCR sample in relation to date of hospital admission. Cases were reviewed using a structured gap analysis tool to identify key learning points. These were discussed in weekly multidisciplinary meetings to gain consensus on learning outcomes, level of harm incurred by the patient and required actions. Learning was then promptly fed back to individual teams and the organisation. Findings: Of the 489 SARS-CoV-2 cases admitted between 10th March and 23rd June 2020, 114 suspected HCA cases (23.3%) were reviewed; 58/489 (11.8%) were ultimately deemed to be HCA. Five themes were identified: individual patient vulnerability, communication, IPC implementation, policy issues and organisational response. Adaptations to policies based on these reviews were completed within the course of the initial phase of the pandemic. Conclusion: This approach enabled timely learning and implementation of control measures and policy development.

Rebooting medical education with virtual grand rounds during the COVID-19 pandemic.

Social distancing during the coronavirus disease 2019 (COVID-19) pandemic has necessitated drastic changes in the practice of hospital medicine, including the cancellation of many educational activities. At the same time, the emergence of a new disease with a rapidly evolving knowledge base has mandated timely educational updates. To resolve this conflict in our hospital, we substituted 'traditional' grand rounds with 'virtual' grand rounds delivered over Zoom, consisting of a local situation report and operational update, followed by a specialty-specific clinical presentation on management of COVID-19. Attendance was greatly increased (mean 384 attendees) compared to traditional grand rounds (mean 44 attendees) and included a diverse audience of medical professionals. Feedback was overwhelmingly positive, with >80% of responders stating that the sessions would or might inform their clinical practice. COVID-19 has therefore provided an opportunity to modernise grand rounds, and develop a new model matching the needs of medical education beyond the pandemic.

Admission COVID-19 clinical risk assessment for guiding patient placement and diagnostic testing strategy.

INTRODUCTION: Without universal access to point-of-care SARS-CoV-2 testing, many hospitals rely on clinical judgement alone for identifying cases of COVID-19 early. METHODS: Cambridge University Hospitals NHS Foundation Trust introduced a 'traffic light' clinical judgement aid to the COVID-19 admissions unit in mid-March 2020. Ability to accurately predict COVID-19 was audited retrospectively across different stages of the epidemic. RESULTS: One SARS-CoV-2 PCR positive patient (1/41, 2%) was misallocated to a 'green' (non-COVID-19) area during the first period of observation, and no patients (0/32, 0%) were mislabelled 'green' during the second period. 33 of 62 (53%) labelled 'red' (high risk) tested SARS-CoV-2 PCR positive during the first period, while 5 of 22 (23%) 'red' patients were PCR positive in the second. CONCLUSION: COVID-19 clinical risk stratification on initial assessment effectively identifies non-COVID-19 patients. However, diagnosing COVID-19 is challenging and risk of overcalling COVID-19 should be recognised, especially when background prevalence is low.

Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT.

BACKGROUND: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. OBJECTIVE: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. DESIGN: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. SETTING: Twenty-six NHS hospitals. PARTICIPANTS: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). INTERVENTIONS: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. RESULTS: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. LIMITATIONS: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. CONCLUSIONS: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. FUTURE WORK: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91566927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Treatment of bone and joint infection usually requires a long course of antibiotics. Doctors usually give these by injection through a vein (intravenously) for the first 4­6 weeks, rather than by mouth (orally). Although intravenous (IV) administration is more expensive and less convenient for patients, most doctors believe that it is more effective. However, there is little evidence to support this. The OVIVA (Oral Versus IntraVenous Antibiotics) trial set out to challenge this assumption. A total of 1054 patients from 26 UK hospitals were randomly allocated to receive the first 6 weeks of antibiotic therapy either intravenously or orally. Irrespective of the route of administration, the choice of antibiotic was left to an infection specialist so as to ensure that the most appropriate antibiotics were given. Patients were followed up for 1 year. Thirty-nine participants were lost to follow-up. Among the remaining 1015 participants, treatment failure occurred in 14.6% of those treated intravenously and 13.2% of those treated with PO antibiotics. This difference could easily have occurred by chance. Even if it was not by chance, the difference does not suggest that PO therapy is associated with worse outcomes than IV therapy and is too small to conclude that PO therapy is better than IV therapy. Participants in the IV group stayed in hospital longer and 10% of them had complications related to the IV line used for administering the antibiotics. In addition, their treatment was, overall, more expensive. We conclude that PO antibiotic therapy has no disadvantages for the early management of bone and joint infection. It is also cheaper and associated with fewer complications.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Management of the Infected Total Hip Arthroplasty.

In the United Kingdom approximately 80,000 total hip arthroplasties are undertaken on an average each year. The popularity and demand for this operation are continually increasing. Our understanding of arthroplasty surgery and its complications has evolved greatly, and as a result infection rates are undeniably at an all-time low. The increasing volume of operations being performed does, however, mean that we still continue to see an increased number of cases of infection. There is no doubt that periprosthetic joint infection (PJI) poses a complex clinical and diagnostic predicament to clinicians. Delay in the diagnosis and treatment of PJI can not only be detrimental in terms of patient morbidity, but it also poses a significant financial burden to health care institutions. It is therefore in the best interest of the patient, surgeon, and institution to optimize the diagnosis and treatment of this devastating complication. There remains considerable variability in terms of approach to diagnosis and treatment of PJI among orthopedic surgeons. In this review, we will, therefore, examine in detail the current body of evidence available on PJI. We will discuss the most robust and up-to-date methods of diagnosis and offer a comparison of management strategies.

Acute schistosomiasis in travelers: 14 years' experience at the Hospital for Tropical Diseases, London.

We report 79 cases of acute schistosomiasis. Most of these cases were young, male travelers who acquired their infection in Lake Malawi. Twelve had a normal eosinophil count at presentation and 11 had negative serology, although two had neither eosinophilia nor positive serology when first seen. Acute schistosomiasis should be considered in any febrile traveler with a history of fresh water exposure in an endemic area once malaria has been excluded.

Leishmaniasis.

Leishmaniasis is an uncommon infectious disease in the UK with a variety of clinical presentations. Physicians should remember to consider this diagnosis in patients with an appropriate travel history (including the Mediterranean basin) and seek help with diagnostics from a specialised parasitology laboratory. Treatment regimens may be unfamiliar to the general physician, and thus should also be discussed with an expert.

The benefit of supplementary feeding for wasted Malawian adults initiating ART.

Food insecurity is considered to be an important contributor to HIV associated wasting in sub-Saharan Africa. Low body mass index (BMI) is a strong risk factor for early mortality during antiretroviral therapy (ART). Nutritional supplementation has become standard of care in wasted patients starting ART in many countries in the region, but there is no unequivocal evidence base for this intervention. Against this background, we performed a retrospective study to compare food supplementation versus no nutritional intervention in wasted adults starting ART in Blantyre, Malawi. All patients received free nevirapine, lamivudine, and stavudine. Participants in an effectiveness trial of two food supplements received either corn-soy blend (CSB) or ready-to-use food spread (RUFS) during the first 14 weeks of ART. Results were compared with a historical control group receiving no food supplement that was part of an observational cohort study of outcomes of the same ART regimen. Characteristics on initiation of ART were similar in the three groups, except the use of cotrimoxazole prophylaxis which was more frequent in the food-supplemented groups. Linear regression analysis showed that increase in BMI was greatest in the RUFS group and better in the CSB group than in those receiving no food supplementation at 14 weeks. These differences were no longer significant at 26 weeks. Lower BMI, CD4 count and hemoglobin, WHO clinical stage IV, male gender, and not receiving cotrimoxazole prophylaxis were independent risk factors for mortality at 14 and 26 weeks in the logistic regression analysis. Supplementary food use was not directly associated with improved survival.