Impact of Hemodialysis on Sleep Disorders in Patients With End-Stage Renal Disease in a Tertiary Care Academic Hospital.

INTRODUCTION: Although hemodialysis (HD) has prolonged the survival of patients with end-stage renal disease (ESRD), it has also adversely affected the sleep and emotional state of these patients. We evaluated the impact of HD on sleep duration, quality, and other sleep-related disorders. METHODS: We recruited consecutive adult patients visiting our tertiary care dialysis unit. We included only ESRD patients who had an estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73m2. We excluded patients with unrelated comorbidities or on medications that could affect sleep. Basic demographic information, anthropometric data, and appropriate lab investigations were obtained. Objective information related to their sleep duration and quality was asked using a predefined proforma. Subjective sleep scores were obtained by using the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). For comparison, the patients were divided into HD and conservative treatment (CT) groups based on their treatment modality. The baseline characteristics of the patients were noted. The Shapiro-Wilk test was used to test normality. Correlations were obtained by using Student's t-test for parameters that were normally distributed and the Mann-Whitney-Wilcoxon test for those that were not. RESULTS: Of the 56 patients we studied, 59% were males. The average age and body mass index (BMI) were 45.7 years and 20.98 kg/m2, respectively. Overall, 41% of patients were assigned to the HD group, and the remaining to the CT group. The CT group had fewer comorbidities compared to the HD group. The average sleep duration was similar in both groups (HD: 6.64 hours, CT: 6.49 hours). There was a weak-to-moderate positive correlation between the sleep scores. Overall, one-half of the patients had excessive daytime sleepiness (EDS) (46.43%) and insomnia (48.21%), and two-thirds of them were poor sleepers (66.07%). Symptoms suggestive of sleep-disordered breathing (SDB) were seen in 25% of patients, restless legs syndrome (RLS) in 19.64% of patients, and periodic limb movement disorder (PLMD) in 44.64% of patients. Patients undergoing HD had poorer sleep quality compared to the CT group (p=0.038). The odds of developing poor sleep were 3.6 times higher in the HD group. CONCLUSION: This cross-sectional study focuses on the quantification of objective and subjective deterioration of sleep quality in ESRD patients on HD. The prevalence of EDS (63.64%), insomnia (51.52%), and poor sleep quality (84.84%) in the HD group was more than the previously reported values. The PSQI, ESS, and ISI scores were higher in HD patients, indicating poorer sleep quality. Our study highlights the underestimation of sleep disorders in HD patients in underserved areas. The results warrant a meticulous evaluation of the same by a keen nephrologist, followed by referral to sleep providers where necessary.

MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects.

Rationale: Efficient labeling methods for mesenchymal stem cells (MSCs) are crucial for tracking and understanding their behavior in regenerative medicine applications, particularly in cartilage defects. MegaPro nanoparticles have emerged as a potential alternative to ferumoxytol nanoparticles for this purpose. Methods: In this study, we employed mechanoporation to develop an efficient labeling method for MSCs using MegaPro nanoparticles and compared their effectiveness with ferumoxytol nanoparticles in tracking MSCs and chondrogenic pellets. Pig MSCs were labeled with both nanoparticles using a custom-made microfluidic device, and their characteristics were analyzed using various imaging and spectroscopy techniques. The viability and differentiation capacity of labeled MSCs were also assessed. Labeled MSCs and chondrogenic pellets were implanted into pig knee joints and monitored using MRI and histological analysis. Results: MegaPro-labeled MSCs demonstrated shorter T2 relaxation times, higher iron content, and greater nanoparticle uptake compared to ferumoxytol-labeled MSCs, without significantly affecting their viability and differentiation capacity. Post-implantation, MegaPro-labeled MSCs and chondrogenic pellets displayed a strong hypointense signal on MRI with considerably shorter T2* relaxation times compared to adjacent cartilage. The hypointense signal of both MegaPro- and ferumoxytol-labeled chondrogenic pellets decreased over time. Histological evaluations showed regenerated defect areas and proteoglycan formation with no significant differences between the labeled groups. Conclusion: Our study demonstrates that mechanoporation with MegaPro nanoparticles enables efficient MSC labeling without affecting viability or differentiation. MegaPro-labeled cells show enhanced MRI tracking compared to ferumoxytol-labeled cells, emphasizing their potential in clinical stem cell therapies for cartilage defects.

The development of an integrated environment-human risk approach for the prioritisation of antibiotics for policy decisions.

Environmental contamination with antibiotic residues has caused significant concern. Antibiotics are continually emitted into the environment which potentially threatens environmental and human health, particularly, the risk in the development of antibiotic resistance. A list of priority antibiotics in the environment is essential for eco-pharmacovigilance and policy decisions. This study developed a prioritisation system of antibiotics based on their integrated environmental (resistance and ecotoxicity) and human health (resistance and toxicity) risks, considering various aquatic environmental compartments. Data obtained by conducting a systematic review of the literature of antibiotic residues in various aquatic environmental compartments in China was used as an example. The list of priority antibiotics was created by ranking the antibiotics in descending order, based on the risk scores of their a) overall risk, (b) antibiotic resistance risk to environment, (c) ecotoxicity risk, (d) overall environmental risk, (e) antibiotic resistance risk to human health, (f) toxicity risk to human health and (g) overall human health risk. Ciprofloxacin posed the greatest risk and chloramphenicol posed the least risk. The output from this research can be used to implement eco-pharmacovigilance and to develop targeted policies which would prevent / minimise the environmental and human health risks from antibiotic residues. The use of this list of priority antibiotics will allow for a country / region / setting to (a) optimise the use of antibiotics and their prescribing practices, (b) create effective monitoring and mitigation strategies, (c) minimise the discharge of antibiotic residues and (d) focus research efforts.

Multimodal In Vivo Tracking of Chimeric Antigen Receptor T Cells in Preclinical Glioblastoma Models.

OBJECTIVES: Iron oxide nanoparticles have been used to track the accumulation of chimeric antigen receptor (CAR) T cells with magnetic resonance imaging (MRI). However, the only nanoparticle available for clinical applications to date, ferumoxytol, has caused rare but severe anaphylactic reactions. MegaPro nanoparticles (MegaPro-NPs) provide an improved safety profile. We evaluated whether MegaPro-NPs can be applied for in vivo tracking of CAR T cells in a mouse model of glioblastoma multiforme. MATERIALS AND METHODS: We labeled tumor-targeted CD70CAR (8R-70CAR) T cells and non-tumor-targeted controls with MegaPro-NPs, followed by inductively coupled plasma optical emission spectroscopy, Prussian blue staining, and cell viability assays. Next, we treated 42 NRG mice bearing U87-MG/eGFP-fLuc glioblastoma multiforme xenografts with MegaPro-NP-labeled/unlabeled CAR T cells or labeled untargeted T cells and performed serial MRI, magnetic particle imaging, and histology studies. The Kruskal-Wallis test was conducted to evaluate overall group differences, and the Mann-Whitney U test was applied to compare the pairs of groups. RESULTS: MegaPro-NP-labeled CAR T cells demonstrated significantly increased iron uptake compared with unlabeled controls ( P < 0.01). Cell viability, activation, and exhaustion markers were not significantly different between the 2 groups ( P > 0.05). In vivo, tumor T2* relaxation times were significantly lower after treatment with MegaPro-NP-labeled CAR T cells compared with untargeted T cells ( P < 0.01). There is no significant difference in tumor growth inhibition between mice injected with labeled and unlabeled CAR T cells. CONCLUSIONS: MegaPro-NPs can be used for in vivo tracking of CAR T cells. Because MegaPro-NPs recently completed phase II clinical trial investigation as an MRI contrast agent, MegaPro-NP is expected to be applied to track CAR T cells in cancer immunotherapy trials in the near future.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Antibiotic concentrations and antibiotic resistance in aquatic environments of the WHO Western Pacific and South-East Asia regions: a systematic review and probabilistic environmental hazard assessment.

BACKGROUND: Antibiotic resistance poses human health risks, and there are concerns about the effect of environmental antibiotic residues in the selection and spread of antibiotic resistance. The aim of this study was to identify antibiotic residue levels that are likely to select for resistance and relative contributions from different aquatic sources, of various aquatic environmental compartments of the WHO Western Pacific region (WPR) and the WHO South-East Asia region (SEAR), including in China and India. METHODS: A systematic review of empirical studies that measured antibiotic concentrations in aquatic environments, published between 2006 and 2019, and a probabilistic environmental hazard assessments approach, were used to identify antibiotic concentrations that are likely to select for resistance in various aquatic environmental compartments of the WPR and SEAR, including in China and India. The assessment involved the use of measured environmental concentrations and predicted no-effect concentrations (PNECs). FINDINGS: The systematic review found 218 relevant studies of 5230 screened from the WPR and 22 relevant studies of 2625 screened from the SEAR; some of these relevant studies were largely from China (n=168) and India (n=15). 92 antibiotics in the WPR and 45 in the SEAR were detected in various aquatic compartments. Antibiotic concentrations that most likely exceeded PNECs (0-100%) were observed in wastewater, and influents and effluents of wastewater treatment plants. Antibiotic concentrations that most likely exceeded PNECs were also observed in aquatic environmental compartments. The highest risk for the development of resistance was in tap or drinking water of the WPR and China for ciprofloxacin (62·5%). The relative contributions of potential sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing, was determined for each antibiotic. INTERPRETATION: The concentrations of antibiotic residues found in wastewater and wastewater treatment plants of the WPR and SEAR make them potential hotspots for the development of antibiotic resistance, which creates human health risks from environmental exposure via drinking water. These findings can help decision makers to target risk reduction measures against environmental residues of priority antibiotics in high-risk sites, and help to focus research efforts in these world regions. FUNDING: Swedish Research Council.

Pre-operative MRI radiomics model non-invasively predicts key genomic markers and survival in glioblastoma patients.

PURPOSE: Although glioblastoma (GBM) is the most common primary brain malignancy, few tools exist to pre-operatively risk-stratify patients by overall survival (OS) or common genetic alterations. We developed an MRI-based radiomics model to identify patients with EGFR amplification, MGMT methylation, GBM subtype, and OS greater than 12 months. METHODS: We retrospectively identified 235 patients with pathologically confirmed GBMs from the Cancer Genome Atlas (88; TCGA) and MD Anderson Cancer Center (147; MDACC). After two neuroradiologists segmented MRI tumor volumes, we extracted first-order and second-order radiomic features (gray-level co-occurrence matrices). We used the Maximum Relevance Minimum Redundancy technique to identify the 100 most relevant features and validated models using leave-one-out-cross-validation and validation on external datasets (i.e., TCGA). Our results were reported as the area under the curve (AUC). RESULTS: The MDACC patient cohort had significantly higher OS (22 months) than the TCGA dataset (14 months). On both LOOCV and external validation, our radiomics models were able to identify EGFR amplification (all AUCs > 0.83), MGMT methylation (all AUCs > 0.85), GBM subtype (all AUCs > 0.92), and OS (AUC > 0.91 on LOOCV and 0.71 for TCGA validation). CONCLUSIONS: Our robust radiomics pipeline has the potential to pre-operatively discriminate common genetic alterations and identify patients with favorable survival.

Utility of constructed wetlands for treatment of hospital effluent and antibiotic resistant bacteria in resource limited settings: A case study in Ujjain, India.

Increasing generation of wastewater and its indiscriminate disposal is detrimental to human and animal health. Resource-limited settings often struggle for efficient wastewater treatment systems owing to lack of funds and operational difficulties. Therefore, alternative treatment systems involving low expenditure and simplistic operations are need of the hour. Constructed wetlands are one such alternative that can efficiently remove variety of pollutants from wastewater. In this study, we have assessed the utility of constructed wetlands for treatment of hospital wastewater in Ujjain. An in-house wetland system was designed and constructed using Typha latifolia and Phragmites karka. Results showed that wetland was efficient for removal of various physico-chemical and biological contaminants, namely, biochemical-oxygen-demand (77.1%), chemical-oxygen-demand (64.9%), turbidity (68.3%), suspended-solids (63%), total-phosphorus (58.7%), nitrate-nitrogen (33%), fecal coliforms (96.8%), and total coliforms (95.6%). Paired t test revealed that removal efficiencies for various parameters were significantly different among Phragmites, Typha, and control cells (p ≤ 0.05). Study also depicted that most of the bacterial isolates in inlet wastewater were selectively resistant to antibiotics (ciprofloxacin and sulphamethaxazole) as well and these isolates were also removed. Precisely, Typha was fairly suitable for antibiotic resistant bacteria removal. Thus, constructed wetlands were found to be one of the suitable options for wastewater treatment in resource-limited settings. PRACTITIONER POINTS: Constructed wetlands are one of the suitable options for wastewater treatment in resource limited settings. These systems involve wetland vegetation, soil, and associated microbial assemblages to improve the water quality. Typha and Phragmites were found to be efficient for treating the hospital wastewater. Experiments showed that antibiotic resistant bacteria may also be removed through constructed wetland systems. Easy operation, cost effectiveness, and efficiency are important attributes.

Incorporating hearing screening to an otolaryngology surgical mission in the rural Dominican Republic.

INTRODUCTION: Hearing loss disproportionately affects low- and middle-income countries. Children with undiagnosed hearing loss may have difficulty with learning, language development, and behavior. The aim of this study was to understand the extent of hearing loss and common otologic disorders among school-age children in the rural western region of the Dominican Republic and to chronical the early stages of a limited-resource, locally-sustained hearing screening program in tandem with a bi-annual surgical mission. METHODS: Hearing screenings were performed for 528 school-age children (1056 ears, age 5-17 years old) over 5 days in a village hospital in Peralta, DR. Testing initially included otoscopy and screening audiometry. Children who referred or could not be conditioned underwent distortion product otoacoustic emissions (OAEs), and tympanometry. Children who referred following both screening audiometry and OAEs were considered to have hearing loss. Those with normal tympanograms were considered potential hearing aid candidates. RESULTS: Abnormal ear examination/otoscopic results were present in 43 children (8.1%) and included: microtia/atresia, impacted cerumen, ear canal foreign body, serous otitis media, otitis externa, and tympanosclerosis. 55 of 528 school-age children referred following screening audiometry and 7 were unable to condition. Of these 62 children, 56 tolerated OAEs and 20 referred following OAEs (3.8%). Fourteen children had type B or C tympanogram and 6 school-age children who were determined to have chronic otitis media with effusion (COME) underwent myringotomy and pressure equalization tube placement. Ten of 528 children (1.9%) had normal tympanometry and otoscopy, and referred following screening audiometry and OAEs suggesting the patients may be potential hearing aid candidates. CONCLUSIONS: The prevalence of hearing loss in this cohort of children in the rural, western Dominican Republic was high at roughly 4% with roughly 2% of children being potential hearing aid candidates. Nearly 10% of children screened had an abnormal otologic examination; sometimes easily remedied by otolaryngologic intervention. With the support of local leadership, it is feasible to incorporate hearing services into otolaryngology outreach and build locally sustainable programs.

Vascular injury of immature epiphyses impair stem cell engraftment in cartilage defects.

The purpose of our study was to investigate if vascular injury in immature epiphyses affects cartilage repair outcomes of matrix-associated stem cell implants (MASI). Porcine bone marrow mesenchymal stromal stem cells (BMSCs) suspended in a fibrin glue scaffold were implanted into 24 full-thickness cartilage defects (5 mm ø) of the bilateral distal femur of six Göttingen minipigs (n = 12 defects in 6 knee joints of 3 immature pigs; age 3.5-4 months; n = 12 defects in 6 knee joints of 3 mature control pigs; age, 21-28 months). All pigs underwent magnetic resonance imaging (MRI) at 2, 4, 12 (n = 24 defects), and 24 weeks (n = 12 defects). After the last imaging study, pigs were sacrificed, joints explanted and evaluated with VEGF, H&E, van Gieson, Mallory, and Safranin O stains. Results of mature and immature cartilage groups were compared using the Wilcoxon signed-rank test. Quantitative scores for subchondral edema at 2 weeks were correlated with quantitative scores for cartilage repair (MOCART score and ICRS score) at 12 weeks as well as Pineda scores at end of the study, using linear regression analysis. On serial MRIs, mature joints demonstrated progressive healing of cartilage defects while immature joints demonstrated incomplete healing and damage of the subchondral bone. The MOCART score at 12 weeks was significantly higher for mature joints (79.583 ± 7.216) compared to immature joints (30.416 ± 10.543, p = 0.002). Immature cartilage demonstrated abundant microvessels while mature cartilage did not contain microvessels. Accordingly, cartilage defects in immature joints showed a significantly higher number of disrupted microvessels, subchondral edema, and angiogenesis compared to mature cartilage. Quantitative scores for subchondral edema at 2 weeks were negatively correlated with MOCART scores (r = - 0.861) and ICRS scores (r = - 0.901) at 12 weeks and positively correlated with Pineda scores at the end of the study (r = 0.782). Injury of epiphyseal blood vessels in immature joints leads to subchondral bone defects and limits cartilage repair after MASI.

One-stop local and whole-body staging of children with cancer.

Accurate staging and re-staging of cancer in children is crucial for patient management. Currently, children with a newly diagnosed cancer must undergo a series of imaging tests, which are stressful, time-consuming, partially redundant, expensive, and can require repetitive anesthesia. New approaches for pediatric cancer staging can evaluate the primary tumor and metastases in a single session. However, traditional one-stop imaging tests, such as CT and positron emission tomography (PET)/CT, are associated with considerable radiation exposure. This is particularly concerning for children because they are more sensitive to ionizing radiation than adults and they live long enough to experience secondary cancers later in life. In this review article we discuss child-tailored imaging tests for tumor detection and therapy response assessment - tests that can be obtained with substantially reduced radiation exposure compared to traditional CT and PET/CT scans. This includes diffusion-weighted imaging (DWI)/MRI and integrated [F-18]2-fluoro-2-deoxyglucose (18F-FDG) PET/MRI scans. While several investigators have compared the value of DWI/MRI and 18F-FDG PET/MRI for staging pediatric cancer, the value of these novel imaging technologies for cancer therapy monitoring has received surprisingly little attention. In this article, we share our experiences and review existing literature on this subject.

How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol.

Gadolinium chelates have been used as standard contrast agents for clinical MRI for several decades. However, several investigators recently reported that rare Earth metals such as gadolinium are deposited in the brain for months or years. This is particularly concerning for children, whose developing brain is more vulnerable to exogenous toxins compared to adults. Therefore, a search is under way for alternative MR imaging biomarkers. The United States Food and Drug Administration (FDA)-approved iron supplement ferumoxytol can solve this unmet clinical need: ferumoxytol consists of iron oxide nanoparticles that can be detected with MRI and provide significant T1- and T2-signal enhancement of vessels and soft tissues. Several investigators including our research group have started to use ferumoxytol off-label as a new contrast agent for MRI. This article reviews the existing literature on the biodistribution of ferumoxytol in children and compares the diagnostic accuracy of ferumoxytol- and gadolinium-chelate-enhanced MRI. Iron oxide nanoparticles represent a promising new class of contrast agents for pediatric MRI that can be metabolized and are not deposited in the brain.

Validation of Deep Learning-based Augmentation for Reduced 18F-FDG Dose for PET/MRI in Children and Young Adults with Lymphoma.

PURPOSE: To investigate if a deep learning convolutional neural network (CNN) could enable low-dose fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI for correct treatment response assessment of children and young adults with lymphoma. MATERIALS AND METHODS: In this secondary analysis of prospectively collected data (ClinicalTrials.gov identifier: NCT01542879), 20 patients with lymphoma (mean age, 16.4 years ± 6.4 [standard deviation]) underwent 18F-FDG PET/MRI between July 2015 and August 2019 at baseline and after induction chemotherapy. Full-dose 18F-FDG PET data (3 MBq/kg) were simulated to lower 18F-FDG doses based on the percentage of coincidence events (representing simulated 75%, 50%, 25%, 12.5%, and 6.25% 18F-FDG dose [hereafter referred to as 75%Sim, 50%Sim, 25%Sim, 12.5%Sim, and 6.25%Sim, respectively]). A U.S. Food and Drug Administration-approved CNN was used to augment input simulated low-dose scans to full-dose scans. For each follow-up scan after induction chemotherapy, the standardized uptake value (SUV) response score was calculated as the maximum SUV (SUVmax) of the tumor normalized to the mean liver SUV; tumor response was classified as adequate or inadequate. Sensitivity and specificity in the detection of correct response status were computed using full-dose PET as the reference standard. RESULTS: With decreasing simulated radiotracer doses, tumor SUVmax increased. A dose below 75%Sim of the full dose led to erroneous upstaging of adequate responders to inadequate responders (43% [six of 14 patients] for 75%Sim; 93% [13 of 14 patients] for 50%Sim; and 100% [14 of 14 patients] below 50%Sim; P < .05 for all). CNN-enhanced low-dose PET/MRI scans at 75%Sim and 50%Sim enabled correct response assessments for all patients. Use of the CNN augmentation for assessing adequate and inadequate responses resulted in identical sensitivities (100%) and specificities (100%) between the assessment of 100% full-dose PET, augmented 75%Sim, and augmented 50%Sim images. CONCLUSION: CNN enhancement of PET/MRI scans may enable 50% 18F-FDG dose reduction with correct treatment response assessment of children and young adults with lymphoma.Keywords: Pediatrics, PET/MRI, Computer Applications Detection/Diagnosis, Lymphoma, Tumor Response, Whole-Body Imaging, Technology AssessmentClinical trial registration no: NCT01542879 Supplemental material is available for this article. © RSNA, 2021.

Determinants and pathways of healthcare-seeking behaviours in under-5 children for common childhood illnesses and antibiotic prescribing: a cohort study in rural India.

OBJECTIVES: To explore the healthcare-seeking pathways, antibiotic prescribing and determine the sociodemographic factors associated with healthcare-seeking behaviour (HSB) of caregivers for common illnesses in under-5 (U-5) children in rural Ujjain, India. STUDY DESIGN: Prospective cohort study. STUDY SETTING AND STUDY SAMPLE: The cohort included 270 U-5 children from selected six villages in rural demographic surveillance site, of the R.D. Gardi Medical College, Ujjain, Madhya Pradesh, India. A community-based cohort was visited two times weekly for over 113 weeks (August 2014 to October 2016) to record the HSB of caregivers using HSB diaries. Sociodemographic information was also solicited. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: first point of care, healthcare-seeking pathway and quantify antibiotic prescribing for the common acute illnesses. SECONDARY OUTCOME: HSB risk factors were determined using mixed-effects multinomial logistic regression. RESULTS: A total of 60 228 HSB follow-up time points for 270 children were recorded with a total of 2161 acute illness episodes. The most common illnesses found were respiratory tract infections (RTI) (69%) and gastrointestinal tract infections (8%). No healthcare was sought in 33% of illness episodes, mostly for RTIs. The most common healthcare-seeking pathway was to informal healthcare providers (IHCPs, 49% of illness episodes). The adjusted relative risk for obtaining no treatment, home treatment and treatment by IHCPs was higher for RTIs (aRR=11.54, 1.82 and 1.29, respectively), illiterate mothers (aRR=2.86, 2.38 and 1.93, respectively), and mothers who were homemakers (aRR=2.90, 4.17 and 2.10, respectively). Socioeconomic status was associated with HSB, with the highest aRR for no treatment in the lowest two socioeconomic quintiles (aRR=6.59 and 6.39, respectively). Antibiotics were prescribed in 46% (n=670/1450) illness episodes and the majority (85%, n=572/670) were broad spectrum. CONCLUSION: In our rural cohort for many acute episodes of illnesses, no treatment or home treatment was done, which resulted in overall reduced antibiotic prescribing. The most common healthcare-seeking pathway was to visit IHCPs, which indicates that they are major healthcare providers in rural areas. Most of the antibiotics were prescribed by IHCPs and were commonly prescribed for illnesses where they were not indicated.

Ferumoxytol magnetic resonance imaging detects joint and pleural infiltration of bone sarcomas in pediatric and young adult patients.

BACKGROUND: The diagnosis of joint infiltration by a malignant bone tumor affects surgical management. The specificity of standard magnetic resonance imaging (MRI) for diagnosing joint infiltration is limited. During our MRI evaluations with ferumoxytol nanoparticles of pediatric and young adult patients with bone sarcomas, we observed a surprising marked T1 enhancement of joint and pleural effusions in some patients but not in others. OBJECTIVE: To evaluate if nanoparticle extravasation differed between joints and pleura with and without tumor infiltration. MATERIALS AND METHODS: We retrospectively identified 15 pediatric and young adult patients (mean age: 16±4 years) with bone sarcomas who underwent 18 MRI scans at 1 h (n=7) or 24 h (n=11) after intravenous ferumoxytol infusion. Twelve patients also received a gadolinium-enhanced MRI. We determined tumor invasion into the joint or pleural space based on histology (n=11) and imaging findings (n=4). We compared the signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of the joint or pleural fluid for tumors with and without invasion using a Mann-Whitney U test. RESULTS: MRI scans 24 h after intravenous ferumoxytol infusion demonstrated a positive T1 enhancement of the effusion in all joints and pleural spaces with tumor infiltration and no joint or pleural space without infiltration. Corresponding SNR (P=0.004) and CNR (P=0.004) values were significantly higher for joints and pleural spaces with tumor infiltration than without. By contrast, unenhanced MRI, gadolinium-enhanced MRI and 1-h post-contrast ferumoxytol MRI did not show any enhancement of the joint or pleural effusion, with or without tumor infiltration. CONCLUSION: This pilot study suggests that 24-h post-contrast ferumoxytol MRI scans can noninvasively differentiate between joints with and without tumor infiltration.

Superior removal of As(III) and As(V) from water with Mn-doped ß-FeOOH nanospindles on carbon foam.

Arsenic pollution of water is one of the severest environmental challenges threatening human health. Iron-based nanomaterials have been demonstrated effective in arsenic removal. However, they generally suffer from low removal efficiency towards highly toxic As(III), loss of active sites owing to agglomeration, and poor reusability. Herein, we report a carbonized melamine foam supported Mn(IV)-doped ß-FeOOH nanospindles(CF@Mn-FeOOH NSp) for tackling the technical hurdles. The designed CF@Mn-FeOOH NSp appears as a free-standing monolith through a low-cost and straightforward hydrothermal method. The atomic-scale integration of Mn(IV) into ß-FeOOH enables an oxidation-adsorption bifunctionality, where Mn(IV) serves as oxidizer for As(III) and Fe(III) acts as adsorber for As(V). The maximal adsorption capacity for As(V) and As(III) can reach 152 and 107 mg g-1, respectively. Meanwhile, As in simulated high arsenic groundwater can be decreased to below 10 µg L-1 within 24 h. By simple "filtrating-washing", 85% and 82% of its initial adsorption capacity for As(V) and As(III) can be easily recovered even after 5-cycles reuse. Kinetics and isotherm adsorption study indicate that the arsenic adsorption behavior is mainly through chemical bonding during single-layer adsorbing process. The as-prepared CF@Mn-FeOOH offers a scalable, efficient, and recyclable solution for arsenic removal in groundwater and wastewater from mines and industry.

Artificial intelligence enables whole-body positron emission tomography scans with minimal radiation exposure.

PURPOSE: To generate diagnostic 18F-FDG PET images of pediatric cancer patients from ultra-low-dose 18F-FDG PET input images, using a novel artificial intelligence (AI) algorithm. METHODS: We used whole-body 18F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3-30 years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose 18F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose 18F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics. RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p < 0.001). Compared to the ground-truth standard-dose PET, SUVmax values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUVmax values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers' diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa = 0.942) than 6.25% dose scans (kappa = 0.650). CONCLUSIONS: Our CNN model could generate simulated clinical standard 18F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.

Challenges in the Delivery of Rural Otolaryngology Care During the COVID-19 Pandemic.

Though initially spared from the brunt of the COVID-19 pandemic, rural areas in the United States have been ravaged by the disease. With a higher-risk population at baseline and an already strained health care system, rural hospitals face severe challenges in delivering care during the pandemic. In otolaryngology specifically, there has been difficulty in ensuring patient access to care while maintaining safe environments for patients and staff. Partnership between academic medical centers and critical access rural hospitals is urgently needed to help improve care for vulnerable rural populations.

Rural-Urban Disparities in Otolaryngology: The State of Illinois.

OBJECTIVES/HYPOTHESIS: To highlight rural-urban disparities in otolaryngology, and to quantify the disparities in access to otolaryngology specialist care across Illinois. Several studies across disciplines have shown increased prevalence and severity of disease in rural communities, relative to their urban counterparts. There is very little published quantifying a disparity in rural access to otolaryngologists. STUDY DESIGN: Population study. METHODS: Counties in Illinois were classified based on urbanization level on a scale from I (most urban) to VI (least urban) using the 2013 National Center for Health Statistics (NCHS) Urban-Rural Classification scheme. The six urbanization levels include four metropolitan (I-IV) and two nonmetropolitan levels (V and VI). The name and practice location of all registered otolaryngologists in Illinois were collected using the American Academy of Otolaryngology website (ENTnet.org). Population data were recorded from the most recent US Census (2010). RESULTS: Two hundred seventy-eight academy-registered otolaryngologists were identified in Illinois. One hundred fifty-one of these providers were located in a single county categorized as a level I by the NCHS scheme. There are over 18,000 square miles and 600,000 persons living in NCHS level VI counties in Illinois with zero registered otolaryngologists. Overall, metropolitan counties (I-IV) averaged 1.32 otolaryngologists per 100,000 population, whereas nonmetropolitan counties (V and VI) averaged 0.46 otolaryngologists per 100,000 (P < .01). CONCLUSIONS: There is a paucity of academy-certified otolaryngologists with primary practice locations in rural counties of Illinois. There is a significant rural population and massive land area with limited spatial access to otolaryngologic specialist care. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E70-E75, 2021.