Tackling the threat of antimicrobial resistance in neonates and children: outcomes from the first WHO-convened Paediatric Drug Optimisation exercise for antibiotics.

Children and neonates are highly vulnerable to the impact of antimicrobial resistance. Substantial barriers are faced in relation to research and development of antibacterial agents for use in neonates, children, and adolescents aged yonger than 19 years, and focusing finite resources on the most appropriate agents for development and paediatric optimisation is urgently needed. In November and December, 2022, following the successes of previous similar disease-focused exercises, WHO convened the first Paediatric Drug Optimisation (PADO) exercise for antibiotics, aiming to provide a shortlist of antibiotics to be prioritised for paediatric research and development, especially for use in regions with the highest burden of disease attributable to serious bacterial infection. A range of antibiotics with either existing license for children or in clinical development in adults but with little paediatric data were considered, and PADO priority and PADO watch lists were formulated. This Review provides the background and overview of the exercise processes and its outcomes as well as a concise review of the literature supporting decision making. Follow-up actions to implement the outcomes from the PADO for antibiotics process are also summarised. This Review highlights the major beneficial influence the collaborative PADO process can have, both for therapeutic drug class and disease-specific themes, in uniting efforts to ensure children have access to essential medicines across the world.

Multiple micronutrient deficiencies as a long-term complication of bariatric surgery.

Micronutrient deficiencies may develop as a long-term complication of bariatric surgery due to alteration of gut anatomy and disruption of normal gut absorption. Inadequate repletion of essential vitamin and mineral deficiencies can lead to multisystem dysfunction. We present a case of a woman in her 50s, with a history of Roux-en-Y gastric bypass over 10 years ago, who presented with generalised weakness and a diffuse desquamating rash. A punch biopsy performed was compatible with nutritional deficiency. Labs revealed low levels of micronutrients A, B1, B6, C, E, zinc and copper. The patient received intravenous micronutrients and an oral regimen, which improved her symptoms. Unfortunately, the patient died from cardiac arrest secondary to pulmonary oedema. This report highlights the importance of high suspicion of micronutrient deficiency in patients with a history of bariatric surgery and maintaining lifelong nutritional follow-up.

Patient and ward related risk factors in a multi-ward nosocomial outbreak of COVID-19: Outbreak investigation and matched case-control study.

BACKGROUND: Risk factors for nosocomial COVID-19 outbreaks continue to evolve. The aim of this study was to investigate a multi-ward nosocomial outbreak of COVID-19 between 1st September and 15th November 2020, occurring in a setting without vaccination for any healthcare workers or patients. METHODS: Outbreak report and retrospective, matched case-control study using incidence density sampling in three cardiac wards in an 1100-bed tertiary teaching hospital in Calgary, Alberta, Canada. Patients were confirmed/probable COVID-19 cases and contemporaneous control patients without COVID-19. COVID-19 outbreak definitions were based on Public Health guidelines. Clinical and environmental specimens were tested by RT-PCR and as applicable quantitative viral cultures and whole genome sequencing were conducted. Controls were inpatients on the cardiac wards during the study period confirmed to be without COVID-19, matched to outbreak cases by time of symptom onset dates, age within ± 15 years and were admitted in hospital for at least 2 days. Demographics, Braden Score, baseline medications, laboratory measures, co-morbidities, and hospitalization characteristics were collected on cases and controls. Univariate and multivariate conditional logistical regression was used to identify independent risk factors for nosocomial COVID-19. RESULTS: The outbreak involved 42 healthcare workers and 39 patients. The strongest independent risk factor for nosocomial COVID-19 (IRR 3.21, 95% CI 1.47-7.02) was exposure in a multi-bedded room. Of 45 strains successfully sequenced, 44 (97.8%) were B.1.128 and differed from the most common circulating community lineages. SARS-CoV-2 positive cultures were detected in 56.7% (34/60) of clinical and environmental specimens. The multidisciplinary outbreak team observed eleven contributing events to transmission during the outbreak. CONCLUSIONS: Transmission routes of SARS-CoV-2 in hospital outbreaks are complex; however multi-bedded rooms play a significant role in the transmission of SARS-CoV-2.

Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in adults is uncommon using rigorous symptom characterization and follow-up in an acute-care adult hospital outbreak.

Asymptomatic coronavirus disease 2019 (COVID-19) has been reported as a significant driver of COVID-19 outbreaks. Our hospital ward outbreak analysis suggests that comprehensive symptoms and signs assessment, in combination with adequate follow-up, allows a more precise determination of COVID-19 symptoms. Asymptomatic infection was quite uncommon among adults in this setting.

Virus kinetics and biochemical derangements among children with Ebolavirus disease.

Background: A paucity of data is available on virologic and biochemical characteristics of paediatric Ebolavirus disease (EVD), compared to adults. Methods: We conducted a retrospective chart review of children (<16 years old) and a comparator group of young adults (16-44 years) from two treatment centres during the 2018-2020 EVD epidemic in Eastern Democratic Republic of the Congo. Statistical methods included chi-squared and Fisher's exact tests (dichotomous and categorical variables), Mann-Whitney U-test (continuous variables), multivariable linear regression (for determinants of admission viral load), linear mixed-effects models (for analysis of longitudinal viral load), and Cox proportional hazard models (to examine risk factors for mortality). Findings: We included 73 children and 234 adults admitted from April to October 2019. Paediatric patients commonly had electrolytes imbalances: hypokalaemia in 26/73 (36%), hyperkalaemia in 38/73 (52%), and hyponatraemia in 54/73 (74%). Hypoglycaemia occurred in 20/73 (27%), acute kidney injury in 43/73 (59%), and rhabdomyolysis in 35/73 (48%). Biochemical abnormalities were detected in a similar proportion of children and adults. The viral load (VL, log10 copies/mL) at admission (7.2 versus 6.5, p=0.0001), the peak viral load (7.5 versus 6.7, p=<0.0001), and the time for viraemia clearance (16 days versus 12 days, p=<0.0001) were significantly different in children. The duration of hospital stay was prolonged in children (20 versus 16 days, p=<0.0001). Risk factors for mortality in children were: VL >7.6 log10copies/mL, alanine transaminase >525 U/L, C-reactive protein >100 mg/L, blood urea nitrogen >7.5 mmol/L, rhabdomyolysis, and.acute kidney injury. Interpretation: Paediatric EVD patients, like adults, experience multiorgan dysfunction with life-threatening electrolyte imbalances, hypoglycaemia, kidney injury, liver injury, and rhabdomyolysis. Paediatric patients have significantly higher VLs throughout the course of EVD than adults. Funding: This study was not funded.

Risk of transmission of respiratory viruses during aerosol-generating medical procedures (AGMPs) revisited in the COVID-19 pandemic: a systematic review.

BACKGROUND: In many jurisdictions healthcare workers (HCWs) are using respirators for aerosol-generating medical procedures (AGMPs) performed on adult and pediatric populations with all suspect/confirmed viral respiratory infections (VRIs). This systematic review assessed the risk of VRIs to HCWs in the presence of AGMPs, the role respirators versus medical/surgical masks have on reducing that risk, and if the risk to HCWs during AGMPs differed when caring for adult or pediatric patient populations. MAIN TEXT: We searched MEDLINE, EMBASE, Cochrane Central, Cochrane SR, CINAHL, COVID-19 specific resources, and MedRxiv for English and French articles from database inception to September 9, 2021. Independent reviewers screened abstracts using pre-defined criteria, reviewed full-text articles, selected relevant studies, abstracted data, and conducted quality assessments of all studies using the ROBINS-I risk of bias tool. Disagreements were resolved by consensus. Thirty-eight studies were included; 23 studies on COVID-19, 10 on SARS, and 5 on MERS/ influenza/other respiratory viruses. Two of the 16 studies which assessed associations found that HCWs were 1.7 to 2.5 times more likely to contract COVID-19 after exposure to AGMPs vs. not exposed to AGMPs. Eight studies reported statistically significant associations for nine specific AGMPs and transmission of SARS to HCWS. Intubation was consistently associated with an increased risk of SARS. HCWs were more likely (OR 2.05, 95% CI 1.2-3.4) to contract human coronaviruses when exposed to an AGMP in one study. There were no reported associations between AGMP exposure and transmission of influenza or in a single study on MERS. There was limited evidence supporting the use of a respirator over a medical/surgical mask during an AGMP to reduce the risk of viral transmission. One study described outcomes of HCWs exposed to a pediatric patient during intubation. CONCLUSION: Exposure to an AGMP may increase the risk of transmission of COVID-19, SARS, and human coronaviruses to HCWs, however the evidence base is heterogenous and prone to confounding, particularly related to COVID-19. There continues to be a significant research gap in the epidemiology of the risk of VRIs among HCWs during AGMPs, particularly for pediatric patients. Further evidence is needed regarding what constitutes an AGMP.

Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing advanced adenomatous polyps in Black patients.

BACKGROUND: Chemoprevention of colorectal neoplasia with aspirin and statins is under-investigated in Black patients. Since Black patients suffer disproportionately from colon cancer incidence and mortality compared to other populations, we investigated the utility of aspirin and statin in reducing advanced adenomatous polyp (AAP) risk in Black patients. METHODS: We carried out a retrospective cohort study of screening colonoscopies performed at a large urban academic center from 1/1/2011 through 12/31/2019. We analyzed self-identified Black patients with > 1 colonoscopy and no personal history of either inflammatory bowel disease or colon cancer syndromes. Our primary endpoint was first AAP development after index colonoscopy among Black patients taking both aspirin and a statin compared to those taking one or neither medication. We used multivariate logistic regression modeling to investigate our outcomes. RESULTS: We found data on chemoprophylaxis use in 560 patients. The mean observation period between index colonoscopy and AAP identification was 4 years. AAP developed in 106/560 (19%) of our cohort. We found no difference in AAP risk among Black patients taking both chemoprevention medications compared to partial or no chemoprophylaxis (20% vs 18% respectively, p = 0.49). This finding remained after adjusting for age, body mass index, and tobacco use (odds ratio 1.04, 95% CI 0.65-1.67; p = 0.87). CONCLUSIONS: Short-term aspirin-statin chemoprevention did not reduce the risk of AAP development in our cohort of Black patients. Larger and long-term prospective investigations are needed to investigate the utility of chemoprophylaxis in this population. TRIAL REGISTRATION: Not applicable.

Human and novel coronavirus infections in children: a review.

Coronaviruses, seven of which are known to infect humans, can cause a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. Four human coronaviruses (hCoVs)-229E, HKU1, NL63 and OC43-circulate globally, commonly infect children and typically cause mild upper respiratory tract infections. Three novel coronaviruses of zoonotic origin have emerged during the past two decades: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV) and the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. These novel coronaviruses are known to cause severe illness and death predominantly in older adults and those with underlying comorbidities. Consistent with what has been observed during the outbreaks of SARS and MERS, children with COVID-19 are more likely to be asymptomatic or to have mild-to-moderate illness, with few deaths reported in children globally thus far. Clinical symptoms and laboratory and radiological abnormalities in children have been similar to those reported in adults but are generally less severe. A rare multisystem inflammatory syndrome in children (MIS-C) which has resulted in critical illness and some deaths has recently been described. Clinical trials for therapeutics and vaccine development should include paediatric considerations. Children may play an important role in the transmission of infection and outbreak dynamics and could be a key target population for effective measures to control outbreaks. The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined.Abbreviations: 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children's Fund; USA, United States of America; WHO, World Health Organization.

Review of Ebola virus disease in children - how far have we come?

Ebola virus (EBOV) causes an extremely contagious viral haemorrhagic fever associated with high mortality. While, historically, children have represented a small number of total cases of Ebolavirus disease (EVD), in recent outbreaks up to a quarter of cases have been in children. They pose unique challenges in clinical management and infection prevention and control. In this review of paediatric EVD, the epidemiology of past EVD outbreaks with specific focus on children is discussed, the clinical manifestations and laboratory findings are described and key developments in clinical management including specific topics such as viral persistence and breastfeeding while considering unique psychosocial and anthropological considerations for paediatric care including of survivors and orphans and the stigma they face are discussed. In addition to summarising the literature, perspectives based on the authors' experience of EVD outbreaks in the Democratic Republic of the Congo (DRC) are described.Abbreviations: ARDS: acute respiratory distress syndrome; aOR: adjusted odds ratio; ALT: alanine transferase; ALIMA: Alliance for International Medical Action; AST: aspartate transaminase; BUN: blood urea nitrogen; CNS: central nervous system; CUBE: chambre d'urgence biosécurisée pour épidémie; COVID-19: coronavirus disease 2019; Ct: cycle threshold; DRC: Democratic Republic of Congo; ETC: ebola treatment centre; ETU: ebola treatment unit; EBOV: ebola virus; EVD: ebolavirus disease; FEAST: fluid expansion as supportive therapy; GP: glycoprotein; IV: intravenous; MEURI: monitored emergency use of unregistered interventions; NETEC: National Ebola Training and Education Centre; NP: nucleoprotein; ORS: oral rehydration solution; PALM: Pamoja Tulinde Maisha; PREVAIL: Partnership for Research on Ebola Virus in Liberia; PPE: personal protective equipment; PCR: polymerase chain reaction; PEP: post-exposure prophylaxis; RDTs: rapid diagnostic tests; RT: reverse transcriptase; RNA: ribonucleic acid; UNICEF: United Nations International Children's Emergency Fund; USA: United States of America; WHO: World Health Organization.

E-Cigarette Use and Perceptions Among Veterans Receiving Outpatient Treatment in Veterans Affairs Substance Use and Mental Health Clinics.

INTRODUCTION: Individuals with substance use disorders and/or mental health (MH) conditions have higher rates of cigarette smoking than the general population. Electronic nicotine delivery systems (ENDS) while gaining popularity pose health risks. Herein we investigate risk perceptions and attitudes toward e-cigarettes in military Veterans with MH conditions. MATERIALS AND METHODS: Participants included U.S. Veterans receiving services from Veterans Administration MH/substance use disorder clinics in the San Francisco Bay Area (N = 98; 95% male, 44% White, 34% Black/African American), who completed a survey on smoking and health. Results compare attitudes and perceptions regarding e-cigarette use between ever and never e-cigarette users. The study was reviewed by the Institutional Review Board at both the Veterans Administration and University. RESULTS: Most respondents reported being current/past cigarette smokers (91%) and over a third reported having ever used an e-cigarette (38%). Most believed that e-cigarettes are not safe, are potentially dangerous, are potentially addictive if they use every day and are tempting and appealing to youth. Fifty-one percent of ever-users agreed with a statement that e-cigarettes can help people quit smoking regular cigarettes completely, and there was a significant difference in this belief when comparing them with never-users (23% agreed); χ2 = 9.259, P = 0.010. CONCLUSIONS: Proportion of e-cigarette use in this Veteran sample is greater than the general population. We observed high risk perception about e-cigarettes among all respondents and differences in perceived helpfulness of e-cigarettes for quitting in ever-users versus never-users in this sample. More consistent assessment of tobacco use among Veterans, with inclusion of ENDS use, would help inform prevention and treatment priorities, especially as information on health impacts of ENDS surfaces.

Invasive Pulmonary Aspergillosis with Hydropneumothorax in a Patient Taking High-Dose Glucocorticoids.

BACKGROUND Invasive pulmonary aspergillosis (IPA) is a severe form of the fungal infection with relatively high mortality rates. Risk factors that lead to IPA include immunosuppression through corticosteroid use. IPA complicated by hydropneumothorax is rare and its mechanism of formation is unknown. CASE REPORT A 72-year-old woman recently diagnosed with a right frontal meningioma that was managed with dexamethasone presented with a new 3-day history of nonproductive cough, chest pain, and dyspnea and was managed for pneumonia. The patient failed to improve, prompting a follow-up computed tomography scan, which revealed a right middle lobe cavitary lesion. During the workup of this lesion, the patient's hospital course was complicated by hemoptysis and development of a large right hydropneumothorax that was successfully managed with a chest tube. Despite initial resolution of hydropneumothorax, the patient developed a right apical pneumothorax that gradually worsened. Bronchoscopy culture revealed Aspergillus fumigatus, leading to the diagnosis of IPA, which was managed with intravenous voriconazole. CONCLUSIONS Corticosteroid use with subsequent immunosuppression is a risk factor for developing IPA. Clinicians should include IPA in their differential diagnosis for respiratory infections in patients receiving corticosteroids. Although overall prognosis of IPA is poor, outcomes can be improved with early diagnosis, early empiric initiation of antifungals, and withdrawal of immunosuppressive therapy. IPA complicated by hydropneumothorax is a rare phenomenon with a poorly understood mechanism of formation. Based on our case, we propose a mechanism of hydropneumothorax formation from IPA.

Attitudes and beliefs about hand hygiene among paediatric residents: a qualitative study.

BACKGROUND: Despite the knowledge that contaminated hands play an important role in the transmission of healthcare-associated pathogens, and that hand hygiene (HH) reduces the transmission of these organisms, healthcare worker's adherence with HH is poor. OBJECTIVE: To understand the common beliefs and attitudes held by paediatric residents about HH. DESIGN: Qualitative study design. SETTING: Tertiary care paediatric hospital in Edmonton, Canada. METHODS: Semistructured interviews were conducted and themes were identified from interviews. PARTICIPANTS: 22 paediatric residents. RESULTS: Paediatric residents self-reported their HH adherence at 70-99% and perceived hospital-wide adherence at 45-80%. Four major themes were identified during interviews including the importance of role modelling, balancing time spent on HH with other competing factors, self-protection as a driving factor for HH and cues as an important part of habit that stimulate HH. CONCLUSIONS: Staff physicians were viewed as integral to initiating group HH events, but at times, the first person in the room acted as a role model for the rest of the group. In certain instances, such as a cardiac arrest, decreased adherence with HH was viewed as acceptable. Residents engaged in HH to protect their own health. Residents relied on personal cues, which they integrated into their own HH habit. Future HH adherence strategies should ensure that the physician training environments permit the formation of good attitudes and habits towards HH. There are no additional data available.

Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation.

The motility of the gastrointestinal tract is generated by smooth muscle cells and is controlled to a large extent by an intrinsic neural network. A gap of approximately 200 nm usually separates nerve varicosities from smooth muscle cells, which suggests that direct innervation of the smooth muscle by synapses does not occur. Enteric nerves do make synapse-like contact with proposed regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in gap junction contact with smooth muscle cells. The role played by ICC in enteric innervation is controversial. Experimental evidence has been presented in vitro for the hypothesis that nitrergic inhibitory innervation is strongly reduced in the absence of ICC. However, in vivo data appear to dispute that. The present report provides evidence that explains the discrepancy between in vivo and in vitro data and provides evidence that inhibitory neurotransmitters can reach smooth muscle cells without hindrance when ICC are absent. The fundic musculature shows increased responses to substance P-mediated innervation and shows marked spontaneous activity, which is consistent with increased muscle excitability.