Background Children in resource-constrained settings (RCS) have disproportionately high illness and mortality; however, the prevalence in RCS of paediatric acute critical illness (P-ACI; life-threatening conditions that require time-sensitive interventions) is unknown. Most P-ACI can be managed with basic critical care (stabilisation, fluid resuscitation, oxygen, and vital-organ support), but RCS hospitals often lack such essential services. This study estimated the prevalence and examined the aetiology of P-ACI among children at RCS hospitals to support critical care capacity building and inform resource allocation. Methods We conducted a hybrid prospective cohort and multinational point prevalence study of acutely ill or injured children aged 28 days to 14 years who presented to RCS hospitals on four designated days between July 20, 2021, and July 12, 2022. We measured the proportion of participants with P-ACI, applying the definition for acute paediatric critical illness (DEFCRIT) framework for research in resource-variable settings, and followed up admitted patients for hospital outcomes. In participants with P-ACI, we report diagnoses associated with critical illness. We used descriptive statistics to summarise site and cohort data by country sociodemographic category (Socio-demographic Index; SDI) and multivariable logistic regression to assess whether country sociodemographic category was independently associated with P-ACI. Findings The study included 46 sites, 19 countries, and 7538 children, among whom 2651 (352%) were admitted to hospital and 68 died (all-cause mortality 09% [95% CI 07-11]). 985 (131% [95% CI 123-139]) participants had P-ACI. Among all sociodemographic categories, P-ACI prevalence was highest (280% [260-301]; 512 of 1828 participants) in low-SDI countries (p<00001). Mortality among those with P-ACI was 63% (49-80; 62 deaths). The most common P-ACI diagnoses were pneumonia (152 [154%] of 985 participants), sepsis or septic shock (102 [104%]), and malaria (95 [96%]). In an adjusted model, country sociodemographic category was not significantly associated with P-ACI frequency. Among all 68 deaths in the study, 40 (59% [46-71]) occurred within 48 h of presentation. Interpretation P-ACI in RCS hospitals is common, associated with high mortality, disproportionately elevated in low- SDI countries, and associated with conditions that can be managed with basic critical care. This study underlines the need for investment in basic critical care services in RCS to address a major contributor to preventable mortality in hospitalised children.

Background The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally. Methods We will conduct a prospective, observational, multicenter, multinational point prevalence study in sixty-one participating RLS hospitals from North, Central and South America, Africa, Middle East and South Asia with four sampling time points over a 12-month period. Children aged 29 days to 14 years evaluated for acute illness or injury in an emergency department) or directly admitted to an inpatient unit will be enrolled and followed for hospital outcomes and resource utilization for the first seven days of hospitalization. The primary outcome will be prevalence of acute critical illness, which Global PARITY has defined as death within 48 hours of presentation to the hospital, including ED mortality; or admission/transfer to an HDU or ICU; or transfer to another institution for a higher level-of-care; or receiving critical care-level interventions (vasopressor infusion, invasive mechanical ventilation, non-invasive mechanical ventilation) regardless of location in the hospital, among children presenting to the hospital. Secondary outcomes include etiology of critical illness, in-hospital mortality, cause of death, resource utilization, length of hospital stay, and change in neurocognitive status. Data will be managed via REDCap, aggregated, and analyzed across sites. Discussion This study is expected to address the current gap in understanding of the burden, etiology, resource utilization and outcomes associated with pediatric acute and critical illness in RLS. These data are crucial to inform future research and clinical management decisions and to improve global pediatric hospital outcomes.

BACKGROUND:The incidence of 3- and 4-level lumbar arthrodesis is rising due to an aging population, and fusion rates affect clinical success in this population. Pulsed electromagnetic field (PEMF) stimulation is used as an adjunct to increase fusion rates following multilevel arthrodesis. The purpose of the study was to evaluate the fusion rates for subjects who underwent 3- and 4-level lumbar interbody arthrodesis following PEMF treatment. METHODS:In this retrospective, multicenter study, patient charts that listed 3- or 4-level lumbar arthrodesis with adjunctive use of a PEMF device were evaluated. Inclusion criteria included patients who were diagnosed with lumbar degenerative disease, spinal stenosis, and/or spondylolisthesis (grade 1 or 2). A radiographic evaluation of fusion status was performed at 12 months by the treating physicians. Fusion rates were stratified by graft material, surgical interbody approach, and certain clinical risk factors for pseudoarthrosis. RESULTS:A total of 55 patients were identified who had a 12-month follow-up. The radiographic fusion rate was 92.7% (51 patients) at 12 months. There were no significant differences in fusion rates for patients treated with allograft or autograft, for patients with different interbody approaches, or for those with or without certain clinical risk factors. CONCLUSIONS:With modern fusion techniques and PEMF, the overall fusion rate was high following 3- and 4-level lumbar arthrodesis. LEVEL OF EVIDENCE:4. CLINICAL RELEVANCE:PEMF may be a useful adjunct for treatment of patients with surgical risk factors, such as multilevel arthrodesis, and clinical risk factors.

Background. The authors compared the local anesthetic efficacy and safety of an intranasally administered formulation of tetracaine and oxymetazoline (K305) with placebo in adult participants undergoing single dental restorative procedures in teeth nos. 4 through 13.Methods. The authors screened and allocated 150 participants in a double-masked, randomized fashion to either K305 or placebo nasal spray. The authors delivered the study drug as two 0.2-milliliter sprays separated by 4 minutes inside the nostril on the side ipsilateral to the tooth being treated. The authors administered a third 0.2-mL spray, if necessary, and administered 4% articaine with 1: 200,000 epinephrine by means of injection if anesthesia was inadequate. Safety evaluations included participant reports of adverse events, vital signs, and alcohol sniff tests during the 2-hour study period and at a 1-day follow-up visit. The primary efficacy end point was anesthetic success defined as the completion of the dental procedure without the need for rescue injectable local anesthetic. The authors evaluated differences in success rates observed between K305 and placebo by using a 1-sided Fisher exact test.Results. The overall success rates were 88.0% (95% confidence interval, 80.0-93.6) and 28% (95% confidence interval, 16.2-42.5) for K305 and placebo, respectively (P < .0001). The most frequent adverse effects in the K305 group were rhinorrhea (57.0%) and nasal congestion (26.0%). No serious adverse events occurred during this study.Conclusions. K305 was effective and well tolerated during restorative procedures in adult participants.

Introduction A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV) administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic and mucosal compartments, and effective at preventing illness associated with evidence of influenza infection. Methods In two separate studies using the human viral challenge model, subjects were selected to be immunologically naive to A/Panama/2007/1999 (H3N2) virus and then dosed via nasal spray with one of three regimens of P-TIV or placebo. One or two doses, 15 μg or 30 μg, were given either once only or twice 14 days apart (1 x 30 μg, 2 x 30 μg, 2 x 15 μg) and subjects were challenged with A/Panama/2007/1999 (H3N2) virus. Immune responses to the vaccine antigens were measured by haemagglutination inhibition assay (HAI) and nasal wash secretory IgA (sIgA) antibodies. Results Vaccine reactogenicity was mild, predictable and generally consistent with earlier Phase I studies with this vaccine. Seroconversion to A/Panama/2007/1999 (H3N2), following vaccination but prior to challenge, occurred in 57% to 77% of subjects in active dosing groups and 2% of placebo subjects. The greatest relative rise in sIgA, following vaccination but prior to challenge, was observed in groups that received 2 doses. Conclusion Intranasal vaccination significantly protected against influenza (as defined by influenza symptoms combined with A/Panama seroconversion) following challenge with A/Panama/2007/1999 (H3N2). When data were pooled from both studies, efficacy ranged from 58% to 82% in active dosing groups for any influenza symptoms with seroconversion, 67% to 85% for systemic or lower respiratory illness and seroconversion, and 65% to 100% for febrile illness and seroconversion. The two dose regimen was found to be superior to the single dose regimen. In this study, protection against illness associated with evidence of influenza infection (evidence determined by seroconversion) following challenge with virus, significantly correlated with pre-challenge HAI titres (p = 0.0003) and mucosal sIgA (p≤0.0001) individually, and HAI (p = 0.028) and sIgA (p = 0.0014) together. HAI and sIgA levels were inversely related to rates of illness. Trial Registration ClinicalTrials.gov NCT02522754

Background. This double-masked, parallel-design, clinical trial assessed whether a combination nasal spray (K305; 3% tetracaine hydrochloride and 0.05% oxymetazoline hydrochloride) compared with a tetracaineonly spray and a placebo spray would be safer and superior in producing local anesthesia sufficient to complete a direct restorative procedure in maxillary nonmolar teeth.Methods. The authors randomized eligible patients to receive K305 spray (n = 44), tetracaine hydrochloride spray (n = 44), or a placebo solution (n = 22). The authors compared the incidence of the primary efficacy end point-completion of the procedure without rescue local anesthetic-by means of a 1-tailed Fisher exact test.Results. The end point incidence was 84.1% (95% confidence interval [CI], 69.9-93.4) with K305, 27.3% (95% CI, 15.0-42.8) with tetracaine only, and 27.3% (95% CI, 10.7-50.2) with placebo (P <.001 for K305 versus tetracaine only and versus placebo). Combination spray was associated with statistically significant but transient increases in blood pressure. The most frequent adverse events were rhinorrhea and nasal congestion, which resolved within 2 hours after treatment and occurred more often in the K305 group and tetracaine-only group.Conclusions. In this study population, the K305 combination nasal spray was safe and more effective in attaining pulpal anesthesia of maxillary teeth from pre-molar to premolar compared with tetracaine-only and placebo sprays.Practical Implications. The combination nasal spray might represent a valuable alternative to injected local anesthetic for patients undergoing invasive maxillary dental procedures.