Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.

Antimicrobial Stewardship in Cystic Fibrosis.

The chronic airway infection and inflammation characteristic of cystic fibrosis (CF) ultimately leads to progressive lung disease, the primary cause of death in persons with CF (pwCF). Despite many recent advances in CF clinical care, efforts to preserve lung function in many pwCF still necessitate frequent antimicrobial use. Incorporating antimicrobial stewardship (AMS) principles into management of pulmonary exacerbations (PEx) would facilitate development of best practices for antimicrobial utilization at CF care centers. However, AMS can be challenging in CF given the unique aspects of chronic, polymicrobial infection in the CF airways, lack of evidence-based guidelines for managing PEx, limited utility for antimicrobial susceptibility testing, and increased frequency of adverse drug events in pwCF. This article describes current evidence-based antimicrobial treatment strategies for pwCF, highlights the potential for AMS to beneficially impact CF care, and provides practical strategies for integrating AMS programs into the management of PEx in pwCF.

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Politics and political determinants of health policy and systems research funding in Latin America and the Caribbean.

Objectives and importance of study: The importance of health policy and systems research (HPSR) has been acknowledged since 2004 and was recognised by the United Nations World Health Assembly in 2005. However, many factors influence its development. This paper aims to analyse the impact of politics and political determinants on HPSR funding in selected countries of Latin America and the Caribbean. METHODS: Using a standardised protocol, we performed an analysis of available data and financing structures for health research and HPSR, based on research in eight countries, including interviews with key stakeholders (n = 42). RESULTS: Dollar depreciation and gross national product growth in the region may play a role in how governments fund research. There have been shifts in the political spectrum in governments, which have affected research coordination and funding in positive and negative ways. HPSR funding in some countries was dependent on budget decisions and although some have improved funding, others have regressed by decreasing funding or have completely cancelled financing mechanisms. Caribbean countries rely mainly on institutional funding. HPSR is recognised as important but remains underfunded; stakeholders believed it should be used more in decision making. CONCLUSION: Although HPSR is recognised as valuable for decision making and policy development, it does not have the financial support required to flourish in Latin America and the Carribean. Data on health research financing were not easy to access. There was little or no evidence of published reports or papers about research financing, health research funding, and HPSR funding in particular in the studied countries. Because of the fragility of health systems highlighted by the coronavirus disease 2019 (COVID-19) pandemic, HPSR should be of great relevance and value to both policy makers and funders.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Impact of a Best Practice Advisory for Pediatric Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Infectious diseases (ID) consultation and optimal antibiotic therapy improve outcomes in Staphylococcus aureus bacteremia (SAB). Data on strategies to improve adherence to these practices in children are limited. METHODS: This was a quasi-experimental study evaluating the impact of an electronic medical record (EMR)-based best practice advisory (BPA) for SAB, recommending ID consult and optimal antibiotic therapy based on rapid mecA gene detection. Inpatients < 21 years old with SAB before (January 2015-July 2017) and after (August 2017-December 2018) BPA implementation were included. Primary outcome was receipt of ID consult. Secondary outcomes included receipt of optimal therapy, time to ID consult and optimal therapy, recurrent SAB, and 30-day all-cause mortality. ID consultation rates pre- and postimplementation were compared using interrupted time series (ITS) analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to optimal therapy were calculated using Cox regression. RESULTS: We included 99 SAB episodes (70 preintervention, 29 postintervention). Preintervention, 48 (68.6%) patients received an ID consult compared to 27 (93.1%) postintervention, but this was not statistically significant on ITS analysis due to a preexisting trend of increasing consultation. Median hours to optimal therapy decreased from 26.1 to 5.5 (P = .03), most notably in patients with methicillin-sensitive S. aureus (MSSA) (42.2 to 10.8; P < .01). On Cox regression, BPA implementation was associated with faster time to optimal therapy (HR, 3.22 [95% CI, 1.04-10.01]). CONCLUSIONS: Implementation of an EMR-based BPA for SAB resulted in faster time to optimal antibiotic therapy, particularly for patients with MSSA. ID consultation increased throughout the study period and was not significantly impacted by the BPA.

A systematic review to investigate whether Angiotensin-(1-7) is a promising therapeutic target in human heart failure.

Context. Heart failure (HF) is a common condition causing much morbidity and mortality despite major advances in pharmacological and device therapies. Preclinical data suggest a cardioprotective role of Angiotensin-(1-7) in animal models of HF. Objective. Perform a systematic review on the effects of Angiotensin-(1-7) on humans, focusing on HF. Results. 39 studies were included in the review (4 in human HF and (35) in non-HF patients). There is only one intervention study on 8 patients with human HF, using Angiotensin-(1-7), with forearm blood flow (FBF) as the endpoint. Angiotensin-(1-7) caused no significant effect on FBF in this HF study but caused vasodilation in 3 out of 4 non-HF studies. In one other non-HF study, Angiotensin-(1-7) infusion led to a significant increase in blood pressure in normal men; however, effects were <0.03% that of angiotensin II. Cardioprotective effects seen in non-HF studies include for instance beneficial actions against atherosclerosis and myocardial fibrosis. Conclusions. The main finding of our systematic review is that Angiotensin-(1-7) plays an important cardioprotective role in HF in animals and in patients without heart failure. More research is required to test the hypothesis that Angiotensin-(1-7) benefits patients with heart failure.

Intradermal pre-exposure rabies vaccine elicits long lasting immunity.

A retrospective cohort study of current rabies antibody titres from adults who received pre-exposure immunisation administered intradermally between 1994 and 2005, examining the decay in titre over time relative to the interval since last dose, and the total dose received. Participants receiving at least 0.6 ml total dose intradermally of vaccine over at least two clinic visits and all with three clinic visits, were shown to have an adequate titre with measurable levels of antibody indicating sero-conversion above 0.5 IU/ml, irrespective of the time interval since the last dose. No clear relationship was found between time interval since immunisation and the level of antibody. Using a schedule that administers 0.6 ml of rabies vaccine over three clinic visits the boosting interval could be extended towards ten years; substantially cheaper than the standard licensed intramuscular dosing schedule.