Nevin Manimala

Trop Med Int Health. 2023 Oct 21. doi: 10.1111/tmi.13940. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary objective of this study was to ascertain the acceptance, initiation, implementation and treatment completion rates of tuberculosis (TB) preventive therapy (TPT) using 3HP (INH-Rifapentine) among household contacts of microbiologically confirmed drug sensitive TB cases on anti-tubercular treatment under programmatic real-world settings. The secondary objectives were to estimate the prevalence and predictors of latent TB infection (LTBI) in household contacts of the index TB cases. We also ascertained the safety profile of the 3HP TPT regimen in the household contacts.

METHODS: This prospective observational study was conducted at 10 TB chest clinics in Delhi, India during 2022-2023. Household contacts aged 14 and older who tested positive for TB infection on a Tuberculin Skin test were initiated on the 3HP regimen. Logistic regression was performed by including statistically significant independent variables in multiple prediction models. p < 0.05 was considered statistically significant. STATA, version 15.1, was used to compute all analyses.

RESULTS: A total of 1067 (84.68%) eligible contacts of microbiologically confirmed, drug sensitive TB cases underwent screening with tuberculin skin test (TST), 614 (95.6%) LTBI positive contacts accepted the initiation of TPT, and 564 (91.8%) of those initiated on TPT completed the treatment. The major reason for refusal of screening was the lack of perception of risk of TB disease due to asymptomatic status. The prevalence of LTBI positivity through TST was 61.5% (95% CI, 58.5%, 64.4%). Adverse events were reported by 195 (31.8%) contacts initiated on 3HP of which 20 participants discontinued TPT. None of the sociodemographic factors showed a significant association with LTBI positivity (except age) or TPT completion rates.

CONCLUSION: LTBI management with 3HP is feasible among adolescent and adult household contacts in India with high rates of adherence from initiation until treatment completion. The maximum attrition of participants occurred at the time of screening for LTBI using TST.

PMID:37864386 | DOI:10.1111/tmi.13940

Pediatr Dermatol. 2023 Oct 20. doi: 10.1111/pde.15459. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Stiff skin syndrome (SSS) is a rare disorder characterized by “rock hard” indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS.

METHODS: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies.

RESULTS: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site.

CONCLUSION: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.

PMID:37864376 | DOI:10.1111/pde.15459

Eur J Oral Sci. 2023 Oct 20:e12959. doi: 10.1111/eos.12959. Online ahead of print.

ABSTRACT

The present study aimed to compare the microstructure, physical, and mechanical properties of three commercially available dental polychromatic multilayer zirconia materials of uniform composition: Dima Mill Zirconia ML, VITA YZ/ST Multicolor, and VITA YZ/XT Multicolor (with 3, 4, and 5 mol% Y₂ O₃ , respectively); thus, the influence of Y₂ O₃ content on the above properties of the produced materials was experimentally studied. Homogeneous zirconia ceramics with a dense micro- and nanostructure, without pores or defects, were produced after milling the blocks and sintering, which resulted in yttrium-stabilized tetragonal and cubic zirconia. Statistical analysis of the results of measurable magnitudes was performed by the one-way ANOVA test. The increase of Y₂ O₃ content (from 3 to 5 mol%) favored larger grain and crystallite sizes and a decrease of the values of the mechanical properties; yet, the differences were statistically insignificant. Clinically, these differences are expected to have no impact on their function in the oral cavity, both in terms of their fracture propensity and the damage that can be caused to the opposing teeth. Accordingly, the experimental results qualify the polychromic multilayer zirconia ceramics of uniform composition fabricated by milling technology for use in dental restorations.

PMID:37864371 | DOI:10.1111/eos.12959

J Magn Reson Imaging. 2023 Oct 21. doi: 10.1002/jmri.29072. Online ahead of print.

ABSTRACT

BACKGROUND: Deep-learning is widely used for lesion classification. However, in the clinic patient data often has missing images.

PURPOSE: To evaluate the use of generated, duplicate and empty(black) images for replacing missing MRI data in AI brain tumor classification tasks.

STUDY TYPE: Retrospective.

POPULATION: 224 patients (local-dataset; low-grade-glioma (LGG) = 37, high-grade-glioma (HGG) = 187) and 335 patients (public-dataset (BraTS); LGG = 76, HGG = 259). The local-dataset was divided into training (64), validation (16), and internal-test-data (20), while the public-dataset was an independent test-set.

FIELD STRENGTH/SEQUENCE: T1WI, T1WI+C, T2WI, and FLAIR images (1.5T/3.0T-MR), obtained from different suppliers.

ASSESSMENT: Three image-to-image translation generative-adversarial-network (Pix2Pix-GAN) models were trained on the local-dataset, to generate T1WI, T2WI, and FLAIR images. The rating-and-preference-judgment assessment was performed by three human-readers (radiologist (MD) and two MRI-technicians). Resnet152 was used for classification, and inference was performed on both datasets, with baseline input, and with missing data replaced by 1) generated images; 2) duplication of existing images; and 3) black images.

STATISTICAL TESTS: The similarity between the generated and the original images was evaluated using the peak-signal-to-noise-ratio (PSNR) and the structural-similarity-index-measure (SSIM). Classification results were evaluated using accuracy, F1-score and the Kolmogorov-Smirnov test and distance.

RESULTS: For baseline-state, the classification model reached to accuracy = 0.93,0.82 on the local and public-datasets. For the missing-data methods, high similarity was obtained between the generated and the original images with mean PSNR = 35.65,32.94 and SSIM = 0.87,0.91 on the local and public-datasets; 39% of the generated-images were labeled as real images by the human-readers. The classification model using generated-images to replace missing images produced the highest results with mean accuracy = 0.91,0.82 compared to 0.85,0.79 for duplicated and 0.77,0.68 for use of black images; DATA CONCLUSION: The feasibility for inference classification model on an MRI dataset with missing images using the Pix2pix-GAN generated images, was shown. The stability and generalization ability of the model was demonstrated by producing consistent results on two independent datasets.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

PMID:37864370 | DOI:10.1002/jmri.29072

Ear Nose Throat J. 2023 Oct 20:1455613231205991. doi: 10.1177/01455613231205991. Online ahead of print.

ABSTRACT

Background: The association between increased nasal resistance (NR) and obstructive sleep apnea syndrome (OSAS) is controversial. The purpose of this study was to examine nasal ventilation function (NVF) in children with OSAS, with a focus on its pathogenetic role. Methods: Children were recruited and divided into the OSAS group (n = 109) and control group (n = 116). The participants underwent polysomnography (PSG), measurement of NR, and acoustic rhinometry (AR). A combination of intranasal corticosteroids (ICS) and oral montelukast (OM) was administered to 90 children with mild to moderate OSAS for 12 weeks. After excluding participants who dropped out or were lost to follow-up, there were 58 children who responded to the treatment, who were divided into 2 groups-A and B. We compared the size of the tonsil adenoids, the PSG, NR, and AR before and after treatment in the 2 groups. Results: Children aged 6 to 12 years with OSAS had significantly higher NR than the control group (P < .05). The OSAS group had a smaller nasal minimal cross-sectional area (NMCA), nasal cavity volume (NCV) from 0 to 5 cm, and nasopharyngeal volume (NPV) from 6 to 8 cm than the control group, and the difference was statistically significant (P < .05 or P < .01). A total of 58 (84.1%) children responded to the 12-week ICS+OM treatment and 11 (15.9%) children did not respond to the treatment. Effective treatment was achieved in 32 children, as evidenced by a significant reduction in tonsil adenoid size and variations in NR and AR values. There were significant improvements in NR, NMCA, and NCV in the remaining 26 children who were successfully treated, but there was no change in tonsil adenoids and NPV value. Conclusion: NVF may play an important pathogenetic role in children with OSAS.

PMID:37864363 | DOI:10.1177/01455613231205991

J Pharm Pract. 2023 Oct 20:8971900231200900. doi: 10.1177/08971900231200900. Online ahead of print.

ABSTRACT

Background: The optimal method for implementing rapid diagnostic testing (RDT) into clinical practice has not been determined for gram-negative rod (GNR) bacteremia. At our institution, RDT was implemented in conjunction with real-time notification of results to decentralized clinical pharmacists. Objective: To determine the impact of RDT result notification plus real-time clinical pharmacist review on the management of GNR bacteremia. Methods: This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BIOFIRE® Blood Culture Identification 2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were matched based on age, pathogen, and resistance. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Results: This study consisted of 240 patients (n = 120 historical, n = 120 interventional). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. There was no difference in median time to appropriate therapy (0 vs 0 hours, P = 0.28). There was a statistically significant decrease in time to first organism-directed change in therapy (40 vs 11 hours; P < 0.01). Length of stay, days of anti-pseudomonal therapy, and inpatient mortality did not differ between groups. Conclusion: Implementation of RDT plus real-time clinical pharmacist review did not significantly decrease time to appropriate therapy in patients with GNR bacteremia but significantly reduced time to organism-directed antibiotic changes.

PMID:37864345 | DOI:10.1177/08971900231200900

Ear Nose Throat J. 2023 Oct 20:1455613231207291. doi: 10.1177/01455613231207291. Online ahead of print.

ABSTRACT

Objectives: Little is known about the prevalence of epistaxis in children. Existing reports focus on hospitalized children or those presenting to an emergency department. To better understand pediatric epistaxis in clinical practice, we sought out a searchable, representative outpatient database and examined the incidence of epistaxis in children of different ages. Methods: A cross-sectional analysis of data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from the years 2007 to 2011 was performed. The NHAMCS is a Centers for Disease Control and Prevention-curated national sample of data from visits to non-federally employed office-based physicians and health centers. We queried the NHAMCS to determine the cumulative incidence of epistaxis in children of different age groups. The International Classification of Diseases Ninth Revision code 784.7 was chosen to identify epistaxis. Comparisons of rates were performed using the chi-squared test. A P-value of <.05 was considered statistically significant. Results: In total, 55,435,691 children [27,816,237 (50.2%) males, 55,435,691 (77.2%) white] were included. The overall cumulative incidence rate of epistaxis was 2.4/1000 children. Children in the 3- to 5-year range had the highest cumulative incidence of epistaxis (5.0/1000), followed by those in the 6 to 8 (3.0/1000), 9 to 11 (2.0/1000), 0 to 2 (1.9/1000), 12 to 14 (1.6/1000), and 15 to 17 (0.5/1000) year ranges (P < .001). Conclusion: Pediatric epistaxis is common in the office setting (2.4 per 1000 children)-and well above emergency department estimates (1.7 per 1000 people). Children between the ages of 3 to 5 years have the highest cumulative incidence. Epistaxis is sufficiently unusual in infants and the late teens that alternative causes for nasal bleeding should be included in the differential diagnosis.

PMID:37864343 | DOI:10.1177/01455613231207291

J Clin Oncol. 2023 Oct 21:101200JCO2302132. doi: 10.1200/JCO.23.02132. Online ahead of print.

ABSTRACT

PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a PARP inhibitor may improve outcomes, especially in pMMR disease.

METHODS: This phase III, global, double-blind, placebo-controlled trial randomized eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab+olaparib arm). Primary end points were progression-free survival (PFS) for durvalumab and durvalumab+olaparib arms versus control.

RESULTS: 718 patients were randomized. In the intent-to-treat population, statistically significant PFS benefit was observed in the durvalumab (HR, 0.71; 95% CI, 0.57 to 0.89; P=.003) and durvalumab+olaparib arms (HR, 0.55; 0.43 to 0.69; P<.0001) versus control. Pre-specfied, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42; 0.22 to 0.80; HR [durvalumab+olaparib v control], 0.41; 0.21 to 0.75) and pMMR subgroups (HR [durvalumab v control], 0.77; 0.60 to 0.97; HR [durvalumab+olaparib v control] 0.57; 0.44 to 0.73); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63; 0.48 to 0.83; HR [durvalumab+olaparib v control], 0.42; 0.31 to 0.57). Interim overall survival results (maturity ∼28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77; 0.56 to 1.07; P=.120; durvalumab+olaparib v control: HR, 0.59; 0.42 to 0.83; P=.003). The safety profiles of the experimental arms were generally consistent with individual agents.

CONCLUSIONS: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

PMID:37864337 | DOI:10.1200/JCO.23.02132

Cytometry A. 2023 Oct 20. doi: 10.1002/cyto.a.24808. Online ahead of print.

ABSTRACT

Microalgae, small photosynthetic unicells, are of great interest to ecology, ecotoxicology and biotechnology and there is a growing need to investigate the ability of cells to photosynthesize under variable conditions. Current strategies involve hand-operated pulse-amplitude-modulated (PAM) chlorophyll fluorimeters, which can provide detailed insights into the photophysiology of entire populations- or individual cells of microalgae but are typically limited in their throughput. To increase the throughput of a commercially available MICROSCOPY-PAM system, we present the PAM Automation Control Manager (‘PACMan’), an open-source Python software package that automates image acquisition, microscopy stage control and the triggering of external hardware components. PACMan comes with a user-friendly graphical user interface and is released together with a stand-alone tool (PAMalysis) for the automated calculation of per-cell maximum quantum efficiencies (= F_v /F_m ). Using these two software packages, we successfully tracked the photophysiology of >1000 individual cells of green algae (Chlamydomonas reinhardtii) and dinoflagellates (genus Symbiodiniaceae) within custom-made microfluidic devices. Compared to the manual operation of MICROSCOPY-PAM systems, this represents a 10-fold increase in throughput. During experiments, PACMan coordinated the movement of the microscope stage and triggered the MICROSCOPY-PAM system to repeatedly capture high-quality image data across multiple positions. Finally, we analyzed single-cell F_v /F_m with the manufacturer-supplied software and PAMalysis, demonstrating a median difference <0.5% between both methods. We foresee that PACMan, and its auxiliary software package will help increase the experimental throughput in a range of microalgae studies currently relying on hand-operated MICROSCOPY-PAM technologies.

PMID:37864330 | DOI:10.1002/cyto.a.24808

Brief Bioinform. 2023 Sep 22;24(6):bbad369. doi: 10.1093/bib/bbad369.

ABSTRACT

Inference of gene regulatory network (GRN) from gene expression profiles has been a central problem in systems biology and bioinformatics in the past decades. The tremendous emergency of single-cell RNA sequencing (scRNA-seq) data brings new opportunities and challenges for GRN inference: the extensive dropouts and complicated noise structure may also degrade the performance of contemporary gene regulatory models. Thus, there is an urgent need to develop more accurate methods for gene regulatory network inference in single-cell data while considering the noise structure at the same time. In this paper, we extend the traditional structural equation modeling (SEM) framework by considering a flexible noise modeling strategy, namely we use the Gaussian mixtures to approximate the complex stochastic nature of a biological system, since the Gaussian mixture framework can be arguably served as a universal approximation for any continuous distributions. The proposed non-Gaussian SEM framework is called NG-SEM, which can be optimized by iteratively performing Expectation-Maximization algorithm and weighted least-squares method. Moreover, the Akaike Information Criteria is adopted to select the number of components of the Gaussian mixture. To probe the accuracy and stability of our proposed method, we design a comprehensive variate of control experiments to systematically investigate the performance of NG-SEM under various conditions, including simulations and real biological data sets. Results on synthetic data demonstrate that this strategy can improve the performance of traditional Gaussian SEM model and results on real biological data sets verify that NG-SEM outperforms other five state-of-the-art methods.

PMID:37864293 | DOI:10.1093/bib/bbad369