Flap blood glucose measurement for flap monitoring and early detection of circulatory problems.

Postoperative monitoring of skin flaps is subjective and cannot detect early circulatory problems in the flap. Early detection and rapid remedial re-exploration are important for flap salvage. We evaluated flap glucose measurement to monitor the flaps for early detection of circulatory problems. In total, 30 patients underwent cutaneous flap reconstruction. This is an easy, economic, objective, and reliable method for flap monitoring and can detect early venous congestion requiring remedial measures.

Cost-Utility Analysis of Geriatric Assessment and Management in Older Adults With Cancer: Economic Evaluation Within 5C Trial.

PURPOSE: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer. METHODS: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups. RESULTS: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective. CONCLUSION: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Effectiveness of geriatric assessment and management in older cancer patients: a systematic review and meta-analysis.

BACKGROUND: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain. OBJECTIVE: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models. RESULTS: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified. CONCLUSION: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness.

A systematic review of contrast-enhanced computed tomography calcium scoring methodologies and impact of aortic valve calcium burden on TAVI clinical outcomes.

Different methodologies have been used to assess the role of AV calcification (AVC) on TAVI outcomes. This systematic review aims to describe the burden of AVC, synthesize the different methods of calcium score quantification, and evaluate the impact of AVC on outcomes after TAVI. We included studies of TAVI patients who had reported AV calcium scoring by contrast-enhanced multidetector CT and the Agatston method. The impact of calcification on TAVI outcomes without restrictions on follow-up time or outcome type was evaluated. Results were reported descriptively, and a meta-analysis was conducted when feasible. Sixty-eight articles were included, with sample sizes ranging from 23 to 1425 patients. Contrast-enhanced calcium scoring was reported in 30 studies, calcium volume score in 28 studies, and unique scoring methods in two. All studies with calcium volume scores had variable protocols, but most utilized a modified Agatston method with variable attenuation threshold values of 300-850 HU. Eight studies used the Agatston method, with the overall mean AV calcium score in studies published from 2010 to 2012 of 3342.9 AU [95%CI: 3150.4; 3535.4, I2 â€‹= â€‹0%]. The overall mean score was lower and heterogenous in studies published from 2014 to 2020 (2658.9 AU [95% CI: 2517.3; 2800.5, I2 â€‹= â€‹79%]. Most studies reported a positive association between calcium burden and increased risk of adverse outcomes, including implantation of permanent pacemaker (7/8 studies), paravalvular leak (13/13 studies), and risk of aortic rupture (2/2 studies). AVC quantification methodology with contrast-enhanced CT is still variable. AVC negatively impacts TAVI outcomes independently of the quantification method.

Treatment of primitive myxoid mesenchymal tumour of infancy: a management paradigm focusing on surgical nuances.

Primitive myxoid mesenchymal tumour of infancy (PMMTI) is a rare mesenchymal tumour that typically appears in those under 6 months of age and preferentially affects the deep soft tissues of the trunk and paravertebral spinal regions. PMMTI has only recently been described, and there is scarce literature reporting cases regarding the management paradigm of the tumour. We report the case of an 11-week-old male who presented with bilaterally reduced movement and brisk reflexes in his lower limbs, and irritability. Despite numerous radiological investigations, including MRI, PMMTI was only diagnosed upon biopsy and histopathology. Although PMMTI is known to be relatively unresponsive to chemotherapy, we observed a notable decrease in tumour size after a series of chemotherapy sessions. After two-staged surgical resection of the tumour, the patient is currently stable and under close follow-up. In this article, we aim to report on the patient's clinical presentation, investigations, diagnosis, and treatment, while also discussing the findings from a review of the literature pertaining to future approaches in managing PMMTI. Overall, this case highlights the importance of considering PMMTI in the differential diagnosis of deep soft tissue tumours in young infants and the potential for a combination of chemotherapy and surgical resection to be effective in treating this rare tumour.

Diagnostic test accuracy of ultrasound for orbital cellulitis: A systematic review.

BACKGROUND: Periorbital and orbital cellulitis are inflammatory conditions of the eye that can be difficult to distinguish using clinical examination alone. Computer tomography (CT) scans are often used to differentiate these two infections and to evaluate for complications. Orbital ultrasound (US) could be used as a diagnostic tool to supplement or replace CT scans as the main diagnostic modality. No prior systematic review has evaluated the diagnostic test accuracy (DTA) of ultrasound compared to cross-sectional imaging. OBJECTIVE: To conduct a systematic review of studies evaluating the DTA of orbital ultrasound compared with cross-sectional imaging, to diagnose orbital cellulitis. METHODS: MEDLINE, EMBASE, CENTRAL, and Web of Science were searched from inception to August 10, 2022. All study types were included that enrolled patients of any age with suspected or diagnosed orbital cellulitis who underwent ultrasound and a diagnostic reference standard (i.e., CT or magnetic resonance imaging [MRI]). Two authors screened titles/abstracts for inclusion, extracted data, and assessed the risk of bias. RESULTS: Of the 3548 studies identified, 20 were included: 3 cohort studies and 17 case reports/series. None of the cohort studies directly compared the diagnostic accuracy of ultrasound with CT or MRI, and all had high risk of bias. Among the 46 participants, diagnostic findings were interpretable in 18 (39%) cases which reported 100% accuracy. We were unable to calculate sensitivity and specificity due to limited data. In the descriptive analysis of the case reports, ultrasound was able to diagnose orbital cellulitis in most (n = 21/23) cases. CONCLUSION: Few studies have evaluated the diagnostic accuracy of orbital ultrasound for orbital cellulitis. The limited evidence based on low quality studies suggests that ultrasound may provide helpful diagnostic information to differentiate orbital inflammation. Future research should focus studies to determine the accuracy of orbital US and potentially reduce unnecessary exposure to radiation.

Kidney Ultrasonography After First Febrile Urinary Tract Infection in Children: A Systematic Review and Meta-analysis.

Importance: Controversy exists on the clinical utility of kidney ultrasonography after first febrile urinary tract infection (UTI), and clinical practice guideline recommendations vary. Objective: To determine the prevalence of urinary tract abnormalities detected on kidney ultrasonography after the first febrile UTI in children. Data Sources: The MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials databases were searched for articles published from January 1, 2000, to September 20, 2022. Study Selection: Studies of children with first febrile UTI reporting kidney ultrasonography findings. Data Extraction and Synthesis: Two reviewers independently screened titles, abstracts, and full texts for eligibility. Study characteristics and outcomes were extracted from each article. Data on the prevalence of kidney ultrasonography abnormalities were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was prevalence of urinary tract abnormalities and clinically important abnormalities (those that changed clinical management) detected on kidney ultrasonography. Secondary outcomes included the urinary tract abnormalities detected, surgical intervention, health care utilization, and parent-reported outcomes. Results: Twenty-nine studies were included, with a total of 9170 children. Of the 27 studies that reported participant sex, the median percentage of males was 60% (range, 11%-80%). The prevalence of abnormalities detected on renal ultrasonography was 22.1% (95% CI, 16.8-27.9; I2 = 98%; 29 studies, all ages) and 21.9% (95% CI, 14.7-30.1; I2 = 98%; 15 studies, age <24 months). The prevalence of clinically important abnormalities was 3.1% (95% CI, 0.3-8.1; I2 = 96%; 8 studies, all ages) and 4.5% (95% CI, 0.5-12.0; I2 = 97%; 5 studies, age <24 months). Study recruitment bias was associated with a higher prevalence of abnormalities. The most common findings detected were hydronephrosis, pelviectasis, and dilated ureter. Urinary tract obstruction was identified in 0.4% (95% CI, 0.1-0.8; I2 = 59%; 12 studies), and surgical intervention occurred in 1.4% (95% CI, 0.5-2.7; I2 = 85%; 13 studies). One study reported health care utilization. No study reported parent-reported outcomes. Conclusions and Relevance: Results suggest that 1 in 4 to 5 children with first febrile UTI will have a urinary tract abnormality detected on kidney ultrasonography and 1 in 32 will have an abnormality that changes clinical management. Given the considerable study heterogeneity and lack of comprehensive outcome measurement, well-designed prospective longitudinal studies are needed to fully evaluate the clinical utility of kidney ultrasonography after first febrile UTI.

A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.

PURPOSE OF REVIEW: Patients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion. RECENT FINDINGS: Of 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design. Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.

Effectiveness of Single Chest Tube vs Double Chest Tube Application Postdecortication: Prospective Randomized Controlled Study.

BACKGROUND: Draining the chest cavity with 2 tubes is a common practice among thoracic surgeons. This research was conducted in Addis Ababa from March 2021 to May 2022. A total of 62 patients were included. STUDY DESIGN: This study was conducted to investigate the superiority of either single or double tube insertion after decortication. Patients were randomized in a ratio of 1:1. In group A, 2 tubes were inserted; in group B, single 32F tubes were inserted. Statistical analyses were performed using Statistical Package for Social Sciences version 27.0, Student's t test and Pearson chi-square test. RESULTS: The age range of patients was 18 to 70 years, with a mean of 44 ± 14.4434 years; the male to female ratio was 2.9:1. The dominant underlying pathologies were tuberculosis and trauma (45.2% vs 35.5%); the right side was more involved (62.3%). Drain output was 1,465 ± 1,887.9751 mL in group A vs 1,018 ± 802.5662 mL in group B (p value = 0.00001); the duration of drains was 7.5498 ± 11.3137 days in group A vs 3.8730 ± 1.4142 days in group B (p value = 0.000042). The degree of pain was 2.6458 ± 4.2426 vs 2.000 ± 2.1213 in group A and group B, respectively (p value = 0.326757). The length of hospital stay was 21.5818 ± 11.9791 days in group A vs 13.6091 ± 6.2048 days in group B (p value = 0.00001). Group A had air leak of 90.3% vs 74.2% in group B; subcutaneous emphysema was 9.7% in group A and 12.9% in group B. There was no fluid recollection, and no patients required tube reinsertion. CONCLUSIONS: The placement of a single tube after decortication is effective in reducing drain output, time of drain, and hospital stay. There was no association with pain, and there was no effect on other endpoints.

What is the quality of reporting in randomized controlled trials in spinal conditions.

Purpose: Substandard quality across published randomized controlled trials (RCTs) is a major concern. Imperfect reporting has the potential to distort the evidence landscape and waste valuable health-care resources. In this study, we aim to assess the current quality of reporting in the field of spine using a modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist. Materials and Methods: A list of published RCTs in the field of spine disease from January 1, 2013, to December 31, 2020, was built. Two reviewers scored the published RCTs against a modified CONSORT checklist. The mean adjusted CONSORT scores for each study, reporting category, and checklist item were calculated. Results: The mean and median scores across all of the RCTs were 0.72 and 0.74 out of 1.00, respectively. The spectrum of scores was wide, ranging from 0.45 to 0.94. The reporting categories with the lowest score included randomization, blinding, and abstract. The items which were most under-reported included allocation sequence generation, type of randomization used, full trial protocol details, and abstract methodology. The inter-rater reliability between our reviewers was substantial (κ = 0.7, κ = 0.71). Conclusion: Our findings correlate with only a moderate level of compliance to the CONSORT criteria on the quality of reporting for RCTs in spinal conditions. This is in line with previous reports on compliance, both within and outside the field of spinal conditions. Further continued and sustained efforts are still required to enhance the quality and consistency of RCT reporting, ultimately reducing health-care resource wastage and improving patient safety.

Rise of the natural red pigment 'prodigiosin' as an immunomodulator in cancer.

Cancer is a heterogeneous disease with multifaceted drug resistance mechanisms (e.g., tumour microenvironment [TME], tumour heterogeneity, and immune evasion). Natural products are interesting repository of bioactive molecules, especially those with anticancer activities. Prodigiosin, a red pigment produced by Serratia marcescens, possesses inherent anticancer characteristics, showing interesting antitumour activities in different cancers (e.g., breast, gastric) with low or without harmful effects on normal cells. The present review discusses the potential role of prodigiosin in modulating and reprogramming the metabolism of the various immune cells in the TME, such as T and B lymphocytes, tumour-associated macrophages (TAMs), natural killer (NK) cells, and tumour-associated dendritic cells (TADCs), and myeloid-derived suppressor cells (MDSCs) which in turn might introduce as an immunomodulator in cancer therapy.

Pediatric Clinical Classification System for use in Canadian inpatient settings.

BACKGROUND: A classification system that categorizes International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes into clinically meaningful categories is important for pediatric clinical and health services research using administrative data. While a Pediatric Clinical Classification System (PECCS) is available for the United States ICD-10 system (i.e, ICD-10-CM), differences in the ICD-10 system between countries limits PECCS use in Canada. OBJECTIVE: To translate PECCS from ICD-10-CM to ICD-10-CA for use in Canada (PECCS-CA), and examine the utility of PECCS-CA in administrative data of pediatric hospital encounters in Ontario, Canada. METHODS: PECCS was translated by mapping each ICD-10-CA code to its corresponding ICD-10-CM code, based on code description and alphanumeric code, using automated functions in Microsoft Excel. All unmatched ICD-10-CA codes were manually matched to an ICD-10-CM code. The ICD-10-CA codes were mapped to a PECCS category based on the placement of the corresponding ICD-10-CM code. Finally, in this cross-sectional study, the utility of PECCS-CA was examined in pediatric hospital encounters in children <18 years of age with an inpatient or same day surgery encounter, between April 1, 2014 to March 31, 2019 in Ontario. RESULTS: In total, 16,992 ICD-10-CA diagnosis codes were mapped to 781 mutually exclusive condition categories that included pediatric specific conditions and treatments in PECCS-CA. From the 781 categories, 777 (99.5%) were derived from the original PECCS, 3 (0.4%) from merging the original PECCS categories, and 1 (0.1%) was newly developed. The PECCS-CA was applied to health administrative data of 911,732 hospital encounters in children. The most prevalent condition in children was low birth weight (n = 54,100 encounters). CONCLUSION: The PECCS-CA is an open-source classification system which maps ICD-10-CA codes into 781 clinically important pediatric categories. The PECCS-CA can be used for pediatric health services and outcomes research in Canada.

Disengaging the COVID-19 Clutch as a Discerning Eye Over the Inflammatory Circuit During SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the cytokine release syndrome (CRS) and leads to multiorgan dysfunction. Mitochondrial dynamics are fundamental to protect against environmental insults, but they are highly susceptible to viral infections. Defective mitochondria are potential sources of reactive oxygen species (ROS). Infection with SARS-CoV-2 damages mitochondria, alters autophagy, reduces nitric oxide (NO), and increases both nicotinamide adenine dinucleotide phosphate oxidases (NOX) and ROS. Patients with coronavirus disease 2019 (COVID-19) exhibited activated toll-like receptors (TLRs) and the Nucleotide-binding and oligomerization domain (NOD-), leucine-rich repeat (LRR-), pyrin domain-containing protein 3 (NLRP3) inflammasome. The activation of TLRs and NLRP3 by SARS-CoV-2 induces interleukin 6 (IL-6), IL-1ß, IL-18, and lactate dehydrogenase (LDH). Herein, we outline the inflammatory circuit of COVID-19 and what occurs behind the scene, the interplay of NOX/ROS and their role in hypoxia and thrombosis, and the important role of ROS scavengers to reduce COVID-19-related inflammation.

Combining CuAAC reaction enables sialylated Bi- and triantennary pseudo mannose N-glycans for investigating Siglec-7 interactions.

Naturally occurring N-glycans display much diversity in modifications, linkages, and peripheral presentation of the oligosaccharide chain. Despite continued advancements in oligosaccharide synthesis, synthetic access to these natural glycans remains challenging. Biologically relevant complex N-glycan mimetics with various natural and unnatural modifications are an alternate way for investigating glycan-protein interactions. Further supporting this pattern, we report here a new class of sialylated bi- and triantennary pseudo mannose N-glycans reproducing orientation of the underlying glycan chain and branching patterns and replacing the two inner mannopyranosyl units with 1,2,3-triazole rings. Such mimetics are straightforwardly generated by implementing multiple intermolecular Cu(I)-catalyzed azide-alkyne cycloaddition between chemoenzymatically synthesized azido sialosides and rationally designed C-3 and C-6 di-O- or C-2, C-3, and C-6 tri-O-alkynylated mannoside. Human recombinant Siglec-7-Fc fusion protein recognizes almost all sialylated pseudo mannose N-glycans in the microarray. However, a differential Sia-binding pattern was also observed. Given the library size, comparison of pairwise mannose N-glycan combinations showed that biantennary linear α(2,3)α(2,8)- and α(2,6)α(2,8)- or branched α(2,3)α(2,6)-, and triantennary branched α(2,3)α(2,6)-sialyl pseudo N-glycans possess similar binding capabilities and affinity to recombinant Siglec-7-Fc. While the full range of topological mannose arms remain elusive, the bi- and triantennary mimics are simpler structures for interrogating Siglec interactions.

Patient, Caregiver, and Clinician Participation in Prioritization of Research Questions in Pediatric Hospital Medicine.

Importance: The research agenda in pediatric hospital medicine has seldom considered the perspectives of young people, parents and caregivers, and health care professionals. Their perspectives may be useful in identifying questions on topics for research. Objective: To prioritize unanswered research questions in pediatric hospital medicine from the perspectives of young people, parents/caregivers, and health care professionals. Design, Setting, and Participants: Between August 4, 2020, and August 19, 2021, two online surveys and a virtual workshop were conducted, using modified Delphi technique and nominal group technique. Young people, parents/caregivers, and health care professionals with experiences in pediatric hospital medicine in Canada were included. Interventions: The established James Lind Alliance Priority Setting Partnership method was used. In phase 1, a survey collected unanswered questions regarding pediatric hospital medicine via 3 open-ended questions. Survey responses were used to develop summary questions that went through an evidence-checking process. Unanswered questions were brought to a phase 2 interim prioritization survey. The top 10 unanswered research questions in pediatric hospital medicine were established at the final priority setting workshop. Main Outcomes and Measures: Survey responses, top 10 research questions. Results: The phase 1 survey was completed by 188 participants (148 of 167 [89%] females; 17 of 167 [10%] males; mean [SD] age, 39.5 [12.4] years) and generated 495 unanswered research questions and comments, of which 58 were deemed out of scope. The remaining 437 responses were grouped into themes (eg, communication, shared decision-making, health service delivery, and health service management) and then refined to 75 unanswered research questions. Of these 75, only 4 questions had sufficient evidence. To make the number of questions in phase 2 manageable, 21 questions submitted by only 1 respondent were eliminated. Fifty unanswered research questions were included in the phase 2 survey, which was completed by 201 participants (165 of 186 [89%] females; 19 of 186 [10%] males; mean [SD] age, 40.0 [11.0] years). A short list of 16 questions-the top 10 questions from patient partners (youths, parents/caregivers) and clinicians-was presented at the final priority setting workshop and the top 10 questions were prioritized. The top 10 questions focused on the care of special inpatient populations (eg, children with medical complexity), communication, shared decision-making, support strategies in the hospital, mental health supports, shortening length of stay, and supporting Indigenous patients, parents/caregivers, and families. Conclusions and Relevance: This patient-oriented pediatric hospital medicine priority setting partnership identified the most important unanswered research questions focused on the care of children in the hospital. These questions provide a possible roadmap for research on areas deemed important to young people, parents/caregivers, and clinicians.

Theophylline-encapsulated Nile Tilapia fish scale-based collagen nanoparticles effectively target the lungs of male Sprague-Dawley rats.

Nile Tilapia fish scale collagen has high biodegradability, excellent biocompatibility, and low antigenicity. We assessed both the encapsulation efficiency of theophylline into Nile Tilapia fish scale-based collagen nanoparticles and their stability as a pulmonary drug delivery system in male Sprague-Dawley rats. The present study has demonstrated the successful encapsulation of theophylline into the synthesised nanoparticles as shown by spectrophotometric analysis, light microscope, scanning electron microscope, transmission electron microscope, and dynamic light scattering. The antibacterial activity of the nanoparticles improves with increasing their concentrations. Intratracheal treatment of rats using theophylline-encapsulated nanoparticles reduced the levels of creatinine, alanine transaminase, and aspartate transaminase, compared to the control group. Nevertheless, nanoparticles combined with theophylline exhibited no effects on cholesterol and triglycerides levels. Histopathological examination revealed typical uniform and diffuse thickening of the alveolar walls with capillary oedema in treated rats. We concluded that the synthesised collagen nanoparticles appropriately target the lungs of male Sprague-Dawley rats when delivered via a nebuliser, showing good tolerability to lung cells. However, dose ratio of collagen nanoparticles to theophylline needs further evaluation. The nanoprecipitation method may be optimised to involve poorly water-soluble inhaled drugs, and avoid the drawbacks of traditional drug delivery.

Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs.

Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides. The synthesized small library of mannose core-based glycans and linear O-glycans were screened for their binding affinity against h-Siglecs 2, 4, 7, 9, 14, 15, and m-Siglec-15 to explore their structure-based binding preferences. Microarray data revealed that each Siglec showed few distinct yet overlapping specificities. An increase in branching from mono to di or tri antennary did not necessarily lead to increasing affinity. Glycans with the disialoside sequence α(2,3)α(2,8)/α(2,6)α(2,8) showed high specificity and affinity for Siglec-7, and sLex α(2,3) exhibited a strong affinity for Siglec-9. Explicit recognition of α(2,6)α(2,3)- linear and α(2,3)α(2,6)-branched glycans by Siglecs-2, 4, and 15, respectively, suggests that these structures can act as potential candidates for the further development of high-affinity ligands.

Prevalence, Cost, and Variation in Cost of Pediatric Hospitalizations in Ontario, Canada.

Importance: Identifying conditions that could be prioritized for research based on health care system burden is important for developing a research agenda for the care of hospitalized children. However, existing prioritization studies are decades old or do not include data from both pediatric and general hospitals. Objective: To assess the prevalence, cost, and variation in cost of pediatric hospitalizations at all general and pediatric hospitals in Ontario, Canada, with the aim of identifying conditions that could be prioritized for future research. Design, Setting, and Participants: This population-based cross-sectional study used health administrative data from 165 general and pediatric hospitals in Ontario, Canada. Children younger than 18 years with an inpatient hospital encounter between April 1, 2014, and March 31, 2019, were included. Main Outcomes and Measures: Condition-specific prevalence, cost of pediatric hospitalizations, and condition-specific variation in cost per inpatient encounter across hospitals. Variation in cost was evaluated using (1) intraclass correlation coefficient (ICC) and (2) number of outlier hospitals. Costs were adjusted for inflation to 2018 US dollars. Results: Overall, 627 314 inpatient hospital encounters (44.8% among children younger than 30 days and 53.0% among boys) at 165 hospitals (157 general and 8 pediatric) costing $3.3 billion were identified. A total of 408 003 hospitalizations (65.0%) and $1.4 billion (43.8%) in total costs occurred at general hospitals. Among the 50 most prevalent and 50 most costly conditions (of 68 total conditions), the top 10 highest-cost conditions accounted for 55.5% of all costs and 48.6% of all encounters. The conditions with highest prevalence and cost included low birth weight (86.2 per 1000 encounters; $676.3 million), preterm newborn (38.0 per 1000 encounters; $137.4 million), major depressive disorder (20.7 per 1000 encounters; $78.3 million), pneumonia (27.3 per 1000 encounters; $71.6 million), other perinatal conditions (68.0 per 1000 encounters; $65.8 million), bronchiolitis (25.4 per 1000 encounters; $54.6 million), and neonatal hyperbilirubinemia (47.9 per 1000 encounters; $46.7 million). The highest variation in cost per encounter among the most costly medical conditions was observed for 2 mental health conditions (other mental health disorders [ICC, 0.28] and anxiety disorders [ICC, 0.19]) and 3 newborn conditions (intrauterine hypoxia and birth asphyxia [ICC, 0.27], other perinatal conditions [ICC, 0.17], and surfactant deficiency disorder [ICC, 0.17]). Conclusions and Relevance: This population-based cross-sectional study of hospitalized children identified several newborn and mental health conditions as having the highest prevalence, cost, and variation in cost across hospitals. Findings of this study can be used to develop a research agenda for the care of hospitalized children that includes general hospitals and to ultimately build a more substantial evidence base and improve patient outcomes.