Category: Nevin Manimala

Pediatr Emerg Care. 2023 Apr 24. doi: 10.1097/PEC.0000000000002948. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the trend in incidence of pediatric magnet ingestions at 2 large Canadian tertiary pediatric hospitals after reintroduction of magnets to the US marketplace and to evaluate morbidity and mortality related to these ingestions.

METHODS: This was a retrospective study performed in 2 tertiary care pediatric hospitals between 2004 and 2019. We reviewed the charts of all children who presented with a foreign body ingestion and included those with reported magnet ingestion. We characterized all events and compared the incidence rate before and after the US ban was overturned in 2016. Descriptive statistics were used to summarize our results. Incidence rate ratio was calculated using the total number of magnet ingestion cases and total emergency department visits normalized to 100,000 emergency department visits/year.

RESULTS: We screened a total of 6586 ingestions and identified 192 patients with magnet ingestions. The period after the mandatory recall was compared with the period after the US ban revocation yielding an incidence rate ratio of 0.76 for all magnet ingestions (P = 0.15) and 0.73 (P = 0.34) for multiple magnet ingestions. There was, however, a graphical upward trend that immediately followed the US ban revocation. Sixty-nine patients (36%) were admitted to the hospital and 45 (23%) required a procedure to remove the magnet ingested. No deaths occurred.

CONCLUSIONS: Our findings suggest that the overturning of the US ban did not lead to a significant increase in the incidence of rare earth magnet ingestion in 2 large tertiary pediatric hospitals in Canada despite noting a trend upwards.

PMID:37083691 | DOI:10.1097/PEC.0000000000002948

J Clin Psychopharmacol. 2023 Apr 22. doi: 10.1097/JCP.0000000000001679. Online ahead of print.

ABSTRACT

BACKGROUND: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum.

METHODS: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling.

RESULTS: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization.

CONCLUSIONS: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.

PMID:37083542 | DOI:10.1097/JCP.0000000000001679

J Pediatr Gastroenterol Nutr. 2023 Apr 21. doi: 10.1097/MPG.0000000000003796. Online ahead of print.

ABSTRACT

OBJECTIVES: Nonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for NASH. The aims were to: 1. describe pharmacokinetics, safety, and tolerability of oral elafibranor at 2 doses (80 and 120mg) in children 8-17 years and 2. assess changes in aminotransferases.

METHODS: Children with NASH were randomized to open-label elafibranor 80mg or 120mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least one dose. Standard descriptive statistics and PK analyses were performed.

RESULTS: Ten males (mean 15.1yrs, SD 2.2) with NASH were randomized to 80mg (n=5) or 120mg (n=5). Baseline mean ALT was 82 U/L (SD 13) and 87 U/L (SD 20) for 80mg and 120mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80mg and 120mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC0-24, respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.

CONCLUSIONS: Once daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

PMID:37084342 | DOI:10.1097/MPG.0000000000003796

JCO Oncol Pract. 2023 Apr 21:OP2200761. doi: 10.1200/OP.22.00761. Online ahead of print.

ABSTRACT

PURPOSE: Patients with cancer are often hospitalized with complications from cancer and cancer treatment. Many experience a decline in physical functioning, including loss of mobility, which likely contributes to increased length of stay (LOS) and increased readmissions. We aimed to determine whether a mobility program would improve quality of care and decrease health care utilization.

METHODS: We implemented a mobility aide program on an oncology unit in a large academic medical center for all patients without bedrest orders between October 1, 2018, and February 28, 2021. The program consisted of nursing evaluation using the Activity Measure for Post-Acute Care (AMPAC), an ordinal scale ranging from bed rest to ambulating ≥ 250 feet, to quantify mobility. Plan of care was determined in a multidisciplinary manner with physical therapy (PT), nursing, and a mobility aide, who is a medical assistant with enhanced rehabilitation training. Patients were then mobilized two times per day 7 days a week. Using descriptive statistics and mixed effects logistic regression, we evaluated the programs impact on LOS, readmissions, and changes in mobility during this time period compared with the 6-month interval before implementation.

RESULTS: A total of 1,496 hospitalized patients were identified. The odds of hospital readmission within 30 days of discharge was significantly less for those who received the intervention (OR, 0.53; 95% CI, 0.37 to 0.78; P = .001). The odds ratio (OR) of having a final AMPAC score at or above the median was significantly higher for those who received the intervention (OR, 1.60; 95% CI, 1.04 to 2.45; P < .05). There was no significant difference in LOS.

CONCLUSION: Use of this mobility program resulted in a significant decrease in readmissions and maintained or improved patients’ mobility. This demonstrates that non-PT professionals can effectively mobilize hospitalized patients with cancer, thereby decreasing the burden on PT and nursing resources. Future work will evaluate the sustainability of the program and evaluate association with health care costs.

PMID:37084332 | DOI:10.1200/OP.22.00761

Bioinformatics. 2023 Apr 21:btad280. doi: 10.1093/bioinformatics/btad280. Online ahead of print.

ABSTRACT

MOTIVATION: Missense variants are a frequent class of variation within the coding genome, and some of them cause Mendelian diseases. Despite advances in computational prediction, classifying missense variants into pathogenic or benign remains a major challenge in the context of personalized medicine. Recently, the structure of the human proteome was derived with unprecedented accuracy using the artificial intelligence system AlphaFold2. This raises the question of whether AlphaFold2 wild-type structures can improve the accuracy of computational pathogenicity prediction for missense variants.

IMPLEMENTATION: To address this, we first engineered a set of features for each amino acid from these structures. We then trained a random forest to distinguish between relatively common (proxy-benign) and singleton (proxy-pathogenic) missense variants from gnomAD v3.1. This yielded a novel AlphaFold2-based pathogenicity prediction score, termed AlphScore.

RESULTS: Important feature classes used by AlphScore are solvent accessibility, amino acid network related features, features describing the physicochemical environment, and AlphaFold2’s quality parameter (pLDDT). AlphScore alone showed lower performance than existing in silico scores used for missense prediction, such as CADD or REVEL. However, when AlphScore was added to those scores, the performance increased, as measured by the approximation of deep mutational scan data, as well as the prediction of expert-curated missense variants from the ClinVar database. Overall, our data indicate that the integration of AlphaFold2 predicted structures can improve pathogenicity prediction of missense variants.

AVAILABILITY: AlphScore, combinations of AlphScore with existing scores, as well as variants used for training and testing are publicly available.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:37084271 | DOI:10.1093/bioinformatics/btad280

Bioinformatics. 2023 Apr 21:btad192. doi: 10.1093/bioinformatics/btad192. Online ahead of print.

ABSTRACT

SUMMARY: The discovery of differential gene-gene correlations across phenotypical groups can help identify the activation/deactivation of critical biological processes underlying specific conditions. The presented R package, provided with a count and design matrix, extract networks of group-specific interactions that can be interactively explored through a shiny user-friendly interface. For each gene-gene link, differential statistical significance is provided through robust linear regression with an interaction term.

AVAILABILITY: DEGGs is implemented in R and available on GitHub at https://github.com/elisabettasciacca/DEGGs. The package is also under submission on Bioconductor.

PMID:37084249 | DOI:10.1093/bioinformatics/btad192

Eur J Cardiothorac Surg. 2023 Apr 21:ezad160. doi: 10.1093/ejcts/ezad160. Online ahead of print.

ABSTRACT

OBJECTIVES: We aim to develop the first risk prediction models for 30-day mortality for benchmarking outcomes specifically for the Australian and New Zealand patient populations and examine whether machine learning algorithms outperform traditional statistical approaches.

METHODS: Data from the Australia New Zealand Congenital Outcomes Registry for Surgery, which contains information on every paediatric cardiac surgical encounter in Australian and New Zealand for patients aged <18 years between January 2013 to December 2021 was analysed (n = 14,343). The outcome was mortality within the 30-day period following a surgical encounter, with approximately 30% of the observations randomly selected to be used for validation of the final model. Three different ML methods were used, all of which employed 5-fold cross-validation to prevent overfitting, with model performance judged primarily by the area under the receiver operating curve (AUC).

RESULTS: Among the 14,343 30-day periods there were 188 deaths (1.3%). In the validation data, the gradient boosted tree obtained the best performance [AUC = 0.87, 95% CI = (0.82, 0.92); calibration = 0.97 95% confidence intervals = (0.72, 1.27)], outperforming penalised logistic regression and artificial neural networks [AUC of 0.82 and 0.81 respectively]. The strongest predictors of mortality in the GBT were patient weight, STAT score, age, and gender.

CONCLUSIONS: Our risk prediction model outperformed logistic regression and achieved a level of discrimination comparable to the PRAiS2 and STS-CHSD mortality risk models (both which obtained AUC = 0.86). Non-linear ML methods can be used to construct accurate clinical risk prediction tools.

PMID:37084239 | DOI:10.1093/ejcts/ezad160

Clin Exp Ophthalmol. 2023 Apr 21. doi: 10.1111/ceo.14231. Online ahead of print.

ABSTRACT

BACKGROUND: Current modalities for diagnosing carotid cavernous fistula (CCF) are inaccurate in analysing retinal microcirculations and nerve fibre changes. Retinal microvascular and neural alterations occur in CCF patients and can be quantitatively measured using optical coherence tomography angiography (OCTA). We measured the neurovascular changes in the eyes of CCF patients and used OCTA as a supplementary method.

METHODS: This cross-sectional study studied 54 eyes of 27 unilateral CCF subjects and 54 eyes of 27 healthy age- and sex-matched controls. OCTA parameters in the macula and optic nerve head (ONH) were analysed using a one-way analysis of variance with further Bonferroni corrections. Parameters with statistical significance were included in a multivariable binary logistic regression analysis and receiver operating characteristic (ROC) curves were generated.

RESULTS: There was significantly less deep-vessel density (DVD) and ONH-associated capillary density in both eyes of CCF patients than in controls, while the differences between the affected and contralateral eyes were insignificant. The retinal nerve fibre layer and ganglion cell complex thickness were lower in the affected eyes than in the contralateral or controlled eyes. ROC curves identified DVD and ONH-associated capillary density as significant parameters in both eyes of CCF patients.

CONCLUSION: The retinal microvascular circulation was affected in both eyes of unilateral CCF patients. Microvascular alterations occurred before retinal neural damage. This quantitative study suggests a supplementary measurement for diagnosing CCF and detecting early neurovascular impairments.

PMID:37084233 | DOI:10.1111/ceo.14231

Cancer Med. 2023 Apr 21. doi: 10.1002/cam4.5905. Online ahead of print.

ABSTRACT

BACKGROUND: Effective noninvasive biomarkers of gastric cancer (GC) are critical for early detection and improvement of prognosis. We performed genome-wide long non-coding RNA (lncRNA) microarray analysis to identify and validate novel GC biomarkers depending on a high-risk population cohort.

METHODS: LncRNA profiles were described using the Human LncRNA Microarray between GC and control plasma samples. The differential candidate lncRNAs were validated in two stages by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We further evaluated the joint effect between the GC-associated lncRNA and Helicobacter pylori (H. pylori) infection on the risk of cardia and non-cardia GC, respectively.

RESULTS: Different lncRNA expression profiles were identified between GC and control plasma with a total of 1206 differential lncRNAs including 470 upregulated and 736 downregulated in GC compared with the control group. The eight significantly upregulated lncRNAs (RP11-521D12.1, AC011995.3, RP11-5P4.3, RP11-244 K5.6, RP11-422 J15.1, CTD-2306 M5.1, CTC-428G20.2, and AC009133.20) in GC cases both in the present study and a similar microarray screening study by our collaborative team were selected for a two-stage validation. After the large sample size validation, the subjects with higher expression of RP11-244 K5.6 showed a significantly increased risk of GC with an adjusted odds ratio (OR) as 2.68 and 95% confidence interval (CI) as 1.15-6.24. Joint effects between RP11-244 K5.6 expression and H. pylori infection on the risk of GC were evaluated with no statistical significance.

CONCLUSIONS: Our study found different lncRNA expression profiles between GC and control plasma and preliminarily identified RP11-244 K5.6 as a potential noninvasive biomarker for GC screening.

PMID:37084181 | DOI:10.1002/cam4.5905

Head Neck. 2023 Apr 21. doi: 10.1002/hed.27376. Online ahead of print.

ABSTRACT

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data.

METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features.

RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003).

CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

PMID:37084179 | DOI:10.1002/hed.27376