Category: Statistics

Eur J Paediatr Neurol. 2022 Mar 29;38:47-52. doi: 10.1016/j.ejpn.2022.03.007. Online ahead of print.

ABSTRACT

BACKGROUND: Alternating hemiplegia of childhood (AHC) pathophysiology suggests predisposition to sedation and anesthesia complications.

GOALS: Hypotheses: 1) AHC patients experience high rates of sedation-anesthesia complications. 2) ATP1A3 mutation genotype positivity, age, and AHC severity correlate with more severe complications. 3) Prior short QTc correlates with cardiac rhythm complications.

METHODS: Analysis of 34 consecutive AHC patients who underwent sedation or anesthesia. Classification of complications: mild (not requiring intervention), moderate (intervention), severe (intervention, risk for permanent injury or potential life-threatening emergency).

STATISTICS: Fisher Exact test, Spearman correlations.

RESULTS: These patients underwent 129 procedures (3.79 ± 2.75 procedures/patient). Twelve (35%) experienced complications during at least one procedure. Fourteen/129 procedures (11%) manifested one or more complications (2.3% mild, 7% moderate, 1.6% severe). Of the total 20 observed complications, six (33.3%) were severe: apneas (2), seizures (2), bradycardia (1), ventricular fibrillation that responded to resuscitation (1). Moderate complications: non-life-threatening bradycardias, apneas, AHC spells or seizures. Complications occurred during sedation or anesthesia and during procedures or recovery periods. Patients with disease-associated ATP1A3 variants were more likely to have moderate or severe complications. There was no correlation between complications and age or AHC severity. Presence of prior short QTc correlated with cardiac rhythm complications. After this series was analyzed, another patient had severe recurrent laryngeal dystonia requiring tracheostomy following anesthesia with intubation.

CONCLUSIONS: During sedation or anesthesia, AHC patients, particularly those with ATP1A3 variants and prior short QTc, are at risk for complications consistent with AHC pathophysiology. Increased awareness is warranted during planning, performance, and recovery from such procedures.

PMID:35390560 | DOI:10.1016/j.ejpn.2022.03.007

Early Hum Dev. 2022 Apr 1;168:105571. doi: 10.1016/j.earlhumdev.2022.105571. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the variability of overnight oximetry parameters in a group of normal, healthy term infants; to enable the calculation of the number of subjects required to produce reliable reference ranges for neonatal overnight oximetry.

METHODS: A convenience sample of normal, healthy term neonates was recruited. Each had overnight oximetry using the Masimo SET Radical oximeter (data downloaded using Profox software). The report included the number of oxygen desaturation events (an absolute decrease in SpO₂ of 4 or more), and the duration of oxygen saturations <90%.

RESULTS: 21 babies were recruited with data available from 19. 32% were female; 68% born by vaginal delivery; 37% fully breast feeding, 53% bottle and 11% by a combination of both. The mean (SD) GA was 39.2 (0.79) weeks, the mean (SD) BW was 3477 (240) grams. The median (IQR) post-natal age at the time the oximetry recording started was 31 (28-41) hours; four babies were <24 h old. All babies had some desaturation events ranging from 4 to 36 times per hour. On average babies spent 3.0% (SD 2.3) of the time with an SpO₂ < 90% (range 0.12-7.94).

CONCLUSIONS: In a cohort of healthy term neonates, as assessed by overnight oximetry, the mean SpO₂ was 97% (SD 1, range 95-99). All neonates had a number of oxygen desaturation events ranging from 4 to 36 per hour. The mean proportion of time spent with oxygen saturations below 90% was around 3%.

PMID:35390559 | DOI:10.1016/j.earlhumdev.2022.105571

J Clin Neurosci. 2022 Apr 4;100:37-45. doi: 10.1016/j.jocn.2022.03.046. Online ahead of print.

ABSTRACT

PURPOSE: Giant thoracic disc herniations (GTDH) are considered a subgroup of TDHs with worse functional outcomes, a high calcification rate, and a considerable risk of complications. We aimed to determine whether there is a relationship between the extent of calcification of GTDH and outcomes concerning the risk of complications, the surgical technique, and changes in neuromonitoring signals.

METHODS: We present a retrospective analysis of 76 patients undergoing surgery for calcific GTDH. We introduced and defined a radiological definition of the calcified disc into”fully calcified” and “partially calcified.” We performed a statistical analysis between clinical and radiological variables, type of surgical procedure, the extent of excision, neuro-monitoring signals, and outcome, comparing a group of 58 “fully-calcified TDH” patients and 18 “partially-calcified TDH” patients.

RESULTS: Fully calcified TDHs, compared with partially calcified TDHs, do not have significant differences in outcome (worse outcome 4/58-6.9% versus 0/18, p = 0.25) and complications (10/58-17.24% versus 4/18-22.2%, p = 0.63); Fully calcified TDH is associated with a higher risk of alterations in neurophysiological potentials (14/58-24.1% versus 0/18, p = 0.02) and subtotal excision (18/58-31% versus 2/18-11%, p = 0.15), without significant differences between the approaches used.

CONCLUSION: Fully calcified TDH group has a similar outcome and complication rate as the partially calcified TDH group, but they are associated with higher intraoperative neuromonitoring signal changes. We introduced a new classificationsystem that guides the approach and helps tocounsel the patients.

PMID:35390556 | DOI:10.1016/j.jocn.2022.03.046

Clin Res Hepatol Gastroenterol. 2022 Apr 4:101921. doi: 10.1016/j.clinre.2022.101921. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about small bowel capsule endoscopy (SBCE) outcomes in patients with surgically altered anatomy.

AIMS: To assess the feasibility and diagnostic yield of orally ingested SBCE to investigate obscure gastrointestinal bleeding (OGIB) in patients with surgically altered gastric anatomy, compared to native gastric anatomy.

METHODS: 207 patients with OGIB were selected from an open, multicenter, retrospective cohort (SAGA study) and match-paired according to age, gender and bleeding type (overt/occult) to 207 control patients from a randomized controlled trial (PREPINTEST). Primary outcomes were the diagnostic yield (P1 or P2 findings), completion rate (CR), adverse events rate AER, and small bowel transit time (SBTT).

RESULTS: The diagnostic yield was not statistically different between groups (44.9% in SAGA vs 42.5% in control patients). Inflammatory/ulcerated lesions were significantly more frequent in patients with SAGA (43.0% vs 29.3%). The median SBTT was significantly longer in the SAGA group than in control patients (283 vs 206 minutes), with a significantly lower CR (82.6% vs 89.9%); Adverse events were scarce (0.5% vs 0.0%).

CONCLUSION: Patients with surgically altered gastric anatomy should benefit from SBCE investigation for OGIB as much as non-operated patients.

PMID:35390539 | DOI:10.1016/j.clinre.2022.101921

Mol Ther. 2022 Apr 4:S1525-0016(22)00227-1. doi: 10.1016/j.ymthe.2022.03.024. Online ahead of print.

ABSTRACT

The development of new therapeutic avenues that target the early stages of Alzheimer’s disease (AD) is urgently necessary. ADAM10 is a sheddase that is involved in dendritic spine shaping and limits the generation of amyloid-β. ADAM10 endocytosis increases in the hippocampus of AD patients, resulting in the decreased postsynaptic localization of the enzyme. To restore this altered pathway, we developed a cell-permeable peptide (PEP3) with a strong safety profile that is able to interfere with ADAM10 endocytosis, upregulating the postsynaptic localization and activity of ADAM10. After extensive validation, experiments in a relevant animal model clarified the optimal timing of the treatment window. PEP3 administration was effective for the rescue of cognitive defects in APP/PS1 mice only if administered at an early disease stage. Increased ADAM10 activity promoted synaptic plasticity, as revealed by changes in the molecular compositions of synapses and the spine morphology. Even though further studies are required to evaluate efficacy and safety issues of long-term administration of PEP3, these results provide preclinical evidence to support the therapeutic potential of PEP3 in AD.

PMID:35390543 | DOI:10.1016/j.ymthe.2022.03.024

J Acad Nutr Diet. 2022 Apr 4:S2212-2672(22)00175-7. doi: 10.1016/j.jand.2022.03.018. Online ahead of print.

ABSTRACT

BACKGROUND: Accurately estimating portion sizes remains a challenge in dietary assessment. Digital images used in online 24-hour dietary recalls may be conducive to accuracy.

OBJECTIVE: The current analyses were conducted to examine the accuracy of portion size estimation by women with low incomes who completed 24-hour dietary recalls using the online Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) in the Food and Eating Assessment STudy (FEAST) II.

DESIGN: True dietary intake was observed for three meals on one day through a controlled feeding study conducted from May through July, 2016. The following day, participants completed an unannounced 24-hour dietary recall using ASA24, independently or with assistance in a small group setting.

PARTICIPANTS/SETTING: Participants included 302 women aged 18 to 82 years living in the Washington, DC area who met the income thresholds for the Supplemental Nutrition Assistance Program.

MAIN OUTCOME MEASURES: The accuracy of portion size estimation was assessed by comparing the weight truly consumed (observed) and the weight reported for pre-determined categories of foods and beverages.

STATISTICAL ANALYSES PERFORMED: The differences between observed and reported portions were examined and linear regression tested differences by recall condition. Analyses were conducted by condition and repeated with stratification by racial/ethnic identity, education, and body mass index.

RESULTS: On average across foods and beverages, reported portion sizes were 7.4 grams (95% CI, 4.3-10.5) and 6.4 grams (95% CI, 2.8-10.0) higher than observed portion sizes in the independent and assisted conditions, respectively. Portion sizes were overestimated for small pieces and shaped foods in both conditions, as well as for amorphous/soft foods in the assisted condition and underestimated for single unit foods in both conditions. Misestimation was fairly consistent by participants’ race/ethnicity, education, and body mass index, to varying magnitudes.

CONCLUSIONS: Women with low incomes overestimated the amounts of foods and beverages consumed across several categories using online 24-hour dietary recalls with digital images to support portion size estimation. Assistance with ASA24 had little impact on accuracy.

PMID:35390532 | DOI:10.1016/j.jand.2022.03.018

Photodiagnosis Photodyn Ther. 2022 Apr 4:102854. doi: 10.1016/j.pdpdt.2022.102854. Online ahead of print.

ABSTRACT

PURPOSE: To determine the acute and cumulative effect of hyperbaric oxygen therapy (HBOT) on retina and choroid tissue in healthy eyes.

MATERIAL AND METHODS: Thirty-five subjects who were planned to undergo HBOT for non-ophthalmologic indications comprised the population of this prospective study. Central macular thickness (CMT), retinal nerve fiber layer (RNFL), and choroidal thickness (CT) (3 points: subfoveal area, 500 µm nasal and fovea temporal) were measured using spectral-domain optical coherence tomography (SD-OCT) before HBOT and half an hour after the 1st and 20th sessions of HBOT. The subfoveal choroidal area was segmented using ImageJ software with the binarization technique on enhanced depth imaging (EDI) OCT images. Choroidal area (CA), luminal area (LA), and stromal area (SA) were calculated. Choroidal vascularity index (CVI) was determined as the ratio between LA and CA.

RESULTS: The right eyes of 35 patients aged between 22 and 59 years were enrolled in the study. The mean CMT values of the patients were 259.36 ± 22.31 µm, 256.94 ± 22.72 µm, and 254.58 ± 23.02 µm before HBOT, after the 1st session, and after the 20th session, respectively. The change in CMT values before and after HBOT was statistically significant (p=0.001). When the patients’ RNFL, CT, CA, SA, LA, and CVI changes before and after the HBOT were examined, no statistically significant difference was found (p>0.05).

CONCLUSIONS: Our study is the first to jointly evaluate the effect of HBOT on the vascular and stromal components of the choroid and macula in healthy eyes. Due to its thinning effect on the macula, it can be preferred as an adjunctive and facilitating treatment option in addition to current treatments in patients with macular edema due to retinal vascular disorders.

PMID:35390520 | DOI:10.1016/j.pdpdt.2022.102854

J Mol Diagn. 2022 Apr 4:S1525-1578(22)00075-7. doi: 10.1016/j.jmoldx.2022.03.004. Online ahead of print.

ABSTRACT

In minimal residual disease (MRD), where there are exceedingly low target copy numbers, droplet digital PCR (ddPCR) can improve the quantitation. However, we currently lack the standards for ddPCR data analysis and results for MRD interpretation in acute lymphoblastic leukemia (ALL). Here, for Ig/TCR-based MRD quantitation, we propose an objective, statistics-based analytic algorithm. In 161 post-induction samples from 79 children with ALL, we performed MRD quantitation by ddPCR and qPCR using the same markers and primer-probe sets. The ddPCR raw data were analysed using an automated algorithm. For assigning MRD positive/negative status, ddPCR and qPCR results were highly concordant (P<0.0001): 98% (50/51) of qPCR positive were positive by ddPCR, while 95% (61/64) of qPCR negative were also negative by ddPCR. For MRD quantitation, both qPCR and ddPCR were tightly correlated (R²=0.94). Using more DNA (1 μg ×7 vs 630 ng ×3), ddPCR improved the sensitivity of MRD quantitation by one-log₁₀ (median MRD positive cut-off 1.6×10^-5). With the improved sensitivity by ddPCR, 83% (29/35) of positive-not-quantifiable results by qPCR could be assigned with positive/negative MRD status. We also determined that 7 replicates of tested samples and negative controls were optimal for the assay. Compared to qPCR, for Ig/TCR-based MRD quantitation, ddPCR could improve MRD sensitivity by one log₁₀. We proposed an automatable, statistics-based algorithm that minimized inter-operator variance for ddPCR MRD.

PMID:35390515 | DOI:10.1016/j.jmoldx.2022.03.004

Infect Genet Evol. 2022 Apr 4:105279. doi: 10.1016/j.meegid.2022.105279. Online ahead of print.

ABSTRACT

As surges of the COVID-19 pandemic continue globally, including in Palestine, several new SARS-CoV-2 variants have been introduced. This expansion has impacted transmission, disease severity, virulence, diagnosis, therapy, and natural and vaccine-induced immunity. Here, 183 whole genome sequences (WGS) were analyzed, of which 129 were from Palestinian cases, 62 of which were collected in 11 Palestinian districts between October 2020 and April 2021and sequenced completely . A dramatic shift from the wild type to the Alpha variant (B 1.1.7) was observed within a short period of time. Cluster mapping revealed statistically significant clades in two main Palestinian cities, Al-Khalil (Monte Carlo hypothesis test-Poisson model, P = 0.00000000012) and Nablus (Monte Carlo hypothesis test-Poisson model, P = 0.014 and 0.015). The phylogenetic tree showed three main clusters of SARS-CoV-2 with high bootstrap values (>90). However, population genetics analysis showed a genetically homogenous population supported by low Wright’s F-statistic values (Fst <0.25), high gene flow (Nm > 3), and statistically insignificant Tajima’s D values (Tajima’s test, neutrality model prediction, P = 0.02). The Alpha variant, rapidly replaced the wild type, causing a major surge that peaked in April 2021, with an increased COVID-19 mortality rate, especially, in the Al-Khalil and Nablus districts. The source of introduction remains uncertain, despite the minimal genetic variation. The study substantiates the use of WGS for SARS-CoV-2 surveillance as an early warning system to track down new variants requiring effective control.

PMID:35390503 | DOI:10.1016/j.meegid.2022.105279

World Neurosurg. 2022 Apr 4:S1878-8750(22)00416-8. doi: 10.1016/j.wneu.2022.03.123. Online ahead of print.

ABSTRACT

PURPOSE: Immunotherapy has revolutionized cancer treatment in the past decade, but significant hurdles remain. Human studies with immune checkpoint inhibitors (ICIs) targeting programmed cell death protein have demonstrated suboptimal efficacy in the setting of low-grade gliomas (LGG). Identification of mechanisms leading to inadequate anti-tumor immunity is paramount. The current study evaluates and validates barriers to immunotherapy using a novel machine learning algorithm.

METHODS: We utilized The Cancer Genome Atlas (TCGA) to generate expression levels of 28 immune genes related to known immunotherapeutic targets or lymphocyte cytolytic activity. We created training and testing groups and three machine learning models to determine the genes most highly correlated to cytolytic activity (CYT). The three models were multiple regression by exhaustive selection, LASSO, and random forest. We validated computational results by comparing expression of pertinent genes in patient-derived glioma samples.

RESULTS: Our models demonstrated linearity, a low mean-squared error, and consistent results with respect to the most important variables. Expression of ICOS, IDO1, and CD40 were the most important variables in all models and demonstrated positive correlation with CYT. Other variables included TIGIT and CD137. Genetic analysis from three IDH-mutants (IDHm) and three IDH-wild type (IDHwt) patient-derived glioma samples validated TCGA data and demonstrated lower levels of CYT in IDHm gliomas compared to IDHwt.

CONCLUSION: This novel methodology has elucidated three potential targets for immunotherapy development in LGG. We also demonstrated a novel method of analyzing data using advanced statistical techniques that can be further employed in developing treatments for other diseases as well.

PMID:35390499 | DOI:10.1016/j.wneu.2022.03.123