Decision Challenges for Managing Acute Paediatric Infections: Implications for Antimicrobial Resistance.

Overprescribing of antibiotics in paediatrics accounts for a significant proportion of inappropriate antibiotic use in human healthcare, thereby contributing to the global health emergency of antimicrobial resistance. Antimicrobial stewardship efforts are complicated by the unique social dynamics in paediatric healthcare, with a specific challenge being the prominent role of parents and carers who act as intermediaries between prescribers and paediatric patients. In this Perspective article concentrating on healthcare of the United Kingdom, we describe this complicated interplay of different decision stakeholders (patients, parents and prescribers), outline four dimensions of decision challenges (social, psychological, systemic and specific diagnostic and treatment challenges) and provide a number of theory-based strategies for supporting different stakeholders during the decision process, ultimately with the aim of improving antimicrobial stewardship. Key decision challenges for patients and carers include limited knowledge and experience of managing infections, which were exacerbated during the COVID-19 pandemic and frequently result in health anxiety and inappropriate health-seeking behaviours. Challenges for medical prescribers span societal pressures from prominent patient litigation cases, cognitive biases, and system pressures to specific diagnostic problems (e.g., age limitations of current clinical scoring systems). Strategies for mitigating decision challenges in paediatric infection management will need to include a range of context- and stakeholder-specific actions, including improvements of integrated care and public health education as well as better clinical decision tools and access to evidence-based guidelines.

A retrospective cohort study of telephone versus face-to-face clinics for the management of new otology referrals.

PURPOSE: To compare outcomes of telephone and face-to-face consultations for new otology referrals and discuss the wider use of telemedicine in otology. METHODS: Retrospective cohort study including new adult otology referrals to our unit, sampled consecutively between March 2021 and May 2021, seen in either a face-to-face or telephone clinic. Primary outcome measure was the proportion of patients with a definitive management outcome (discharged or added to waiting list for treatment) versus the proportion of patients requiring follow-up for further assessment or review. RESULTS: 150 new patients referred for a routine otology consultation (75 telephone, 75 face-to-face) were included. 53/75 patients (71%) undergoing a face-to-face consultation received a definitive outcome following initial review, versus 22/75 (29%) telephone patients (χ2 < 0.001, OR 5.8). 52/75 (69%) telephone patients were followed up face-to-face for examination. The mean (SD) number of appointments required to reach a definitive outcome was 1.22 (0.58) and 1.75 (0.73) in the face-to-face and telephone cohorts, respectively (p < 0.001). CONCLUSIONS: Telephone clinics in otology have played an important role as part of the COVID19 response. However, they are currently limited by a lack of clinical examination and audiometry. Remote assessment pathways in otology that incorporate asynchronous review of recorded examinations alongside audiometry, either conventional or boothless, may mitigate this problem; however, further research is required.

Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values.

OBJECTIVE: To determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children. DESIGN: Phase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT. SETTING: Tertiary paediatric hospitals. PATIENTS: Children under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive. RESULTS: Phase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%-59%), specificity: 100% (99%-100%), positive predictive value (PPV): 100% (18%-100%) and negative predictive value (NPV): 99% (97%-99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%-92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative. CONCLUSION: The NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings. TRIAL REGISTRATION NUMBER: NCT04629157.

Modelling the asymmetric nexus between carbon emissions and COVID-19: Indian evidence employing NARDL model

After rising for decades, carbon emissions fell in 2020 by 2.3 billion tonnes. The objective of the study is to investigate the effect of COVID-19 on carbon emissions in India by employing the nonlinear autoregressive distributed lag model over the period March 25, 2020, to August 31, 2021. Unit root test confirms that all variables are integrated at order I(0) and I(1). Bounds test supports long-run association amongst the variables. Results of the study validate the asymmetric relationship between COVID-19 determinants and CO2 emissions. It presents that lockdown has significantly reduced the CO2 emissions. This asymmetric relationship indicates that COVID-19 has become the major cause of reduction in greenhouse gases, but this cannot be treated as a permanent solution to environmental destruction. Thus, the study suggested that governments and policymakers should formulate FDI policy on high-tech low carbon technology while preparing a strict environmental access system and promote environmentally sustainable investment through subsidies.

The Association Between Sleep Health and Mood in Sedentary Desk Workers

Introduction Poor sleep, most commonly insufficient sleep duration or low sleep quality, has been linked with disruptions of mood. However, it is unclear how sleep health—more broadly, other multiple dimensions of sleep—is associated with mood. The purpose of this study was to investigate the associations between sleep health and mood in a sample of desk-working sedentary adults. Methods This cross-sectional study used baseline data from inactive adults with desk-based jobs (N=125, 49.6% female, 43.9±10.6 years) who enrolled in an ongoing clinical trial. Sleep was assessed using validated questionnaires and 7 nights of actigraphy. Collectively, these measures were utilized to assess six different sleep dimensions: regularity, satisfaction, alertness, timing, efficiency, duration. Each dimension was categorized as “good” or “poor”. A sleep health score was calculated by summing the number of good dimensions (range: 0-6;higher is better). Mood was assessed using Profile of Mood States (POMS);its 7 subscales (tension, anger, fatigue, depression, esteem-affect, vigor, confusion) were summed (with a constant of 100) to create a Total Mood Disturbance (TMD) score. Multiple linear regression models examined associations between sleep health and mood adjusting for age, gender, and whether pre- or post-COVID-19. Results The mean sleep health score was 4.7±1.1;the mean TMD score was 96.6±18.5. Better sleep health was associated with lesser TMD (β=-0.32, p<0.001) and better mood on each of the POMS subscales (β≥0.18, p<0.05), aside from esteem-related affect (p=0.31). Of the individual sleep dimensions, only satisfaction, alertness, and efficiency were associated with TMD (β≥0.18, p<0.05). Satisfaction was the only individual sleep dimension that was consistently associated with better mood on each subscale (β≥0.17). Alertness, efficiency, and duration were inconsistently associated with individual mood subscales. Regularity and timing were not associated with any mood subscales (p≥0.267 and p≥0.073, respectively). Conclusion Better sleep health was associated with less TMD. Satisfaction was the sleep dimension that consistently associated with each subscale of mood. The cross-sectional, observational design limits casual inference between sleep health and mood disturbance due to a lack of temporality and the potential for residual confounding. Support (If Any) This study was funded by National Institutes of Health (NIH) grants R01HL134809 and R01HL147610.

Mitigation of SARS-CoV-2 transmission at a large public university.

In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal "SHIELD: Target, Test, and Tell" program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed >1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university.

The Impact of the COVID-19 Pandemic on the Workload, Case Mix and hospital Resources at a Tertiary Vascular Unit.

BACKGROUND: The aim of this study was to examine the COVID-19 pandemic and its associated impact on the provision of vascular services, and the pattern of presentation and practice in a tertiary referral vascular unit. METHODS: This is a retrospective observational study from a prospectively maintained data-base comparing two time frames, Period 1(15th March-30th May 2019-P1) and Period 2(15th March-30th May 2020-P2)All the patients who presented for a vascular review in the 2 timeframes were included. Metrics of service and patient care episodes were collected and compared including, the number of emergency referrals, patient encounters, consultations, emergency admissions and interventions. Impact on key hospital resources such as critical care and imaging facilities during the two time periods were also examined. RESULTS: There was an absolute reduction of 44% in the number of patients who required urgent or emergency treatment from P1 to P2 (141 vs 79). We noted a non-significant trend towards an increase in the proportion of patients presenting with Chronic Limb Threatening Ischaemia (CLTI) Rutherford 5&6 (P=0.09) as well as a reduction in the proportion of admissions related to Aortic Aneurysm (P=0.21). There was a significant absolute reduction of 77% in all vascular interventions from P1 to P2 with the greatest reductions noted in Carotid (P=0.02), Deep Venous (P=0.003) and Aortic interventions (P=0.016). The number of lower limb interventions also decreased though there was a significant increase as a relative proportion of all vascular interventions in P2 (P=0.001). There was an absolute reduction in the number of scans performed for vascular pathology; Duplex scans reduced by 86%(P<0.002), CT scans by 68%(P<0.003) and MRIs by 74%(P<0.009). CONCLUSION: We report a decrease in urgent and emergency vascular presentations, admissions and interventions. The reduction in patients presenting with lower limb pathology was not as significant as other vascular conditions, resulting in a significant rise in interventions for CLTI and DFI as a proportion of all vascular interventions. These observations will help guide the provision of vascular services during future pandemics.

Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe.

The coronavirus disease-19 has left a permanent mark on the history of the human race. Severe acute respiratory syndrome coronavirus-2 is a positive-sense single-stranded RNA virus, first reported in Wuhan, China, in December 2019 and from there took over the world. Being highly susceptible to mutations, the virus's numerous variants started to appear, and some were more lethal and infectious than the parent. The effectiveness of the vaccine is also affected severely against the new variant. In this study, the infectious mechanism of the coronavirus is explained with a focus on different variants and their respective mutations, which play a critical role in the increased transmissibility, infectivity, and immune escape of the virus. As India has already faced the second wave of the pandemic, the future outlook on the likeliness of a third wave with respect to the Indian variants such as kappa, delta, and Delta Plus is also discussed. This review article aims to reflect the catastrophe of the variants of SARS-CoV-2 and the possibility of developing even more severe variants in the near future.

Evaluating the impact of antimicrobial stewardship interventions in a UK paediatric emergency department

BackgroundAntimicrobial resistance (AMR) poses a major threat to human health. Although rates of AMR have risen significantly in adults over the past few years, increasing rates of AMR are now being seen in children. Antimicrobial stewardship (AMS) is a highly effective approach to tackling AMR;however few paediatric AMS initiatives have focused on antibiotic prescribing in an Emergency Department (ED) setting. There are data to suggest that rates of antibiotic prescribing for respiratory tract infections (RTIs) is higher in children presenting to emergency departments than in those presenting with comparable disease severity to primary care.ObjectivesThe focus of this study was to evaluate the impact of two sequential antimicrobial stewardship interventions on antibiotic prescribing for children aged <16 years presenting with upper and lower respiratory tract infections to the Paediatric Emergency Department (PED) at Southampton Children’s Hospital.MethodsAntibiotic prescribing data were collected over a 16 week period (03/08/2020–22/11/20). All children with a discharge diagnosis of upper respiratory tract infection (URTI), otitis media, tonsillitis, pneumonia and lower respiratory tract infection (LRTI) were included. Baseline data were collected between weeks 1–7. The 1st AMS intervention was a 15-minute educational session delivered either face to face or virtually to all PED clinicians by a PED consultant (DJ). The educational intervention used informational slide sets to reinforce the principles of judicious antibiotic use and appropriate antibiotic guideline adherence for RTI’s through case-based learning scenarios and quizzes that facilitated group discussion. This intervention was repeated weekly between weeks 8–10, to ensure that all PEM staff were exposed to the intervention. The 2nd intervention, implemented on week 14, involved feedback of personalised antibiotic prescribing data, along with average antibiotic prescribing rates for the department, to each member of PED staff.Results502 children with RTIs presented during the study period. Antibiotic prescribing rates significantly decreased from 28.6% during the pre-intervention period to 20.5% at the end of the study (p<0.05). Antibiotic prescribing for a discharge diagnosis of URTI decreased from 9.3% to 4.8% (p=0.11), for otitis media from 78.9% to 53.8% (p=0.13), for tonsillitis from 71.8% to 48.8% (p=0.03) and for LRTI and pneumonia from 66.7% to 51.7% (p=0.31).ConclusionsThe combination of an educational intervention and individualised feedback of prescribing data was associated with a significant reduction in overall antibiotic prescribing for children with RTIs managed in an ED setting. However, although reductions were seen for individual pathologies, statistical significance was not always reached. This may be due to the relatively small sample size;far fewer children were recruited during the 16 week study period than predicted due to the impact of the COVID pandemic on rates of PED presentations. In general the interventions were easy to implement;however manual interrogation of patient notes was required to collect individual clinician prescribing data, this was labour intensive and would ideally be automated through the use of electronic prescribing systems. Further work is required to show if the findings from this study can be replicated in other settings and if this impact is sustained or requires repeated AMS interventions.

Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents.

OBJECTIVE: To undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years. DESIGN: Narrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020. SETTING: All settings, including hospitalised and community settings. PATIENTS: Children and young people (CYP) under age 20 years with laboratory-proven COVID-19. STUDY REVIEW, DATA EXTRACTION AND QUALITY: Potentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers. MAIN OUTCOME MEASURES: Prevalence of symptoms and signs of COVID-19. RESULTS: 1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion of asymptomatic CYP ranged from 14.6% to 42%. Fever and cough were the the most common symptoms; proportions with fever ranged from 46% to 64.2% and with cough from 32% to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting were infrequent, occurring in less than 10%-20%. CONCLUSIONS: Fever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.

Intestinal Abnormalities in Patients With SARS-CoV-2 Infection: Histopathologic Changes Reflect Mechanisms of Disease.

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.

Impact of COVID-19 Pandemic on the Outcomes in Patients With Critical Limb Threatening Ischaemia and Diabetic Foot Infection.

OBJECTIVE: Examine the impact of COVID-19 pandemic on the outcomes in patients with CLTI or DFI. BACKGROUND: Patients with CLTI and/or DFI are at risk of amputations if not treated in a timely manner. METHODS: We compared the outcomes in patients with CLTI or DFI during 2 periods; Period 1[P1] (15/03/2019-31/05/2019) and period 2[P2] (15/03/ 2020-31/05/2020- corresponding to COVID-19 pandemic). RESULTS: One hundred thirty-nine patients were treated in P1 [mean age 70 years (±11), Male:Female = 102:37] whereas 95 patients were treated in P2 [mean age 67 (±12), Male:Female = 64:31]. The 2 cohorts were matched regarding Rutherford category (P = 0.25) and GLASS classification (P = 0.38). Notably, the time from onset of symptom to clinical presentation was significantly longer [31 (1-105) days vs 27 (0-78) days, (P = 0.017)], whereas the time from presentation to first intervention was significantly shorter [3 (0-61) days vs 5 (0-65) days, (P = 0.013)] in P2 compared to P1. There was a significantly higher white cell count (P = 0.014) and CRP (P = 0.004) on admission in P2. Having treatment for CLTI or DFI in P2 was an independent predictor of worse primary patency rate and freedom from major adverse limb events. At 90 days, amputation-free survival and limb salvage were noticeably worse in P2 compared to P1 (amputation-free survival was 80% and 87% whereas limb salvage was 64% and 72% in P2 and P1, respectively). CONCLUSIONS: Patients with CLTI and DFI experienced a significantly delayed presentation with features of sepsis on admission in P2. Treatment in P2 was a predictor of worse primary patency and freedom from major adverse limb events and therefore close and long follow-up is advisable.

Diet, Gut Microbiota and COVID-19.

Worldwide, millions of individuals have been affected by the prevailing SARS-CoV-2. Therefore, a robust immune system remains indispensable, as an immunocompromised host status has proven to be fatal. In the absence of any specific antiviral drug/vaccine, COVID-19 related drug repurposing along with various other non-pharmacological measures coupled with lockdown have been employed to combat this infection. In this context, a plant based rich fiber diet, which happens to be consumed by a majority of the Indian population, appears to be advantageous, as it replenishes the host gut microbiota with beneficial microbes thereby leading to a symbiotic association conferring various health benefits to the host including enhanced immunity. Further, implementation of the lockdown which has proven to be a good non-pharmacological measure, seems to have resulted in consumption of home cooked healthy diet, thereby enriching the beneficial microflora in the gut, which might have resulted in better prognosis of COVID-19 patients in India in comparison to that observed in the western countries.

COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City.

SARS-CoV-2, the etiologic agent of COVID-19, is a global pandemic with substantial mortality dominated by acute respiratory distress syndrome. We systematically evaluated lungs of 68 autopsies from 3 institutions in heavily hit areas (2 USA, 1 Italy). Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. The cohort consisted of 47 males and 21 females with a median age of 73 years (range 30-96). Co-morbidities were present in most patients with 60% reporting at least three conditions. Tracheobronchitis was frequently present, independent from intubation or superimposed pneumonia. Diffuse alveolar damage (DAD) was seen in 87% of cases. Later phases of DAD were less frequent and correlated with longer duration of disease. Large vessel thrombi were seen in 42% of cases but platelet (CD61 positive) and/or fibrin microthrombi were present at least focally in 84%. Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization. In a subset of cases, virus was detected using different tools (immunohistochemistry for SARS-CoV-2 viral spike protein, RNA in situ hybridization, lung viral culture, and electron microscopy). Virus was seen in airway epithelium and type 2 pneumocytes. IHC or in situ detection, as well as viable form (lung culture positive) was associated with the presence of hyaline membranes, usually within 2 weeks but up to 4 weeks after initial diagnosis. COVID-19 pneumonia is a heterogeneous disease (tracheobronchitis, DAD, and vascular injury), but with consistent features in three centers. The pulmonary vasculature, with capillary microthrombi and inflammation, as well as macrothrombi, is commonly involved. Viral infection in areas of ongoing active injury contributes to persistent and temporally heterogeneous lung damage.