Tag: statistics

J Psychiatr Res. 2021 Mar 6;137:283-289. doi: 10.1016/j.jpsychires.2021.03.003. Online ahead of print.

ABSTRACT

Sparse studies have shown that specific biomarkers of a global DNA methylation status may be related to various mental diseases and states, including: bipolar disorder (BD), anxiety and major depression disorder (MDD). The objective of this study was to analyze potential variation of the above mentioned global methylation status in women with depression. 38 women with a current and clinically confirmed depressive episode suffering from BD type I, type II or MDD and 71 women from the general population and at similar age were recruited for the study. Alu and LINE-1 methylation was assayed with the quantitative methylation-specific PCR technique with TaqMan probes, while the 5-mC and 5-hmC level was determined using the ELISA-based method. Significantly higher levels of 5-mC, Alu and LINE-1 methylation were observed in the women with depression as compared to the controls; while the 5-hmC level revealed to be significantly lower. The BD type I patients presented the highest level of 5-mC of all the women with a depressive episode. 5-mC level in the patients was positively and significantly correlated with the severity of the symptoms of depression. Relationships between Alu or LINE-1 methylation and 5-mC level were statistically significant only in the case of the control women. Alu and LINE-1 methylation do not constitute suitable biomarkers of global DNA methylation in the investigated patients. These findings require confirmation in case-control and prospective epidemiological studies.

PMID:33730603 | DOI:10.1016/j.jpsychires.2021.03.003

Am J Hum Genet. 2021 Mar 10:S0002-9297(21)00058-6. doi: 10.1016/j.ajhg.2021.02.016. Online ahead of print.

ABSTRACT

Tests of association between a phenotype and a set of genes in a biological pathway can provide insights into the genetic architecture of complex phenotypes beyond those obtained from single-variant or single-gene association analysis. However, most existing gene set tests have limited power to detect gene set-phenotype association when a small fraction of the genes are associated with the phenotype and cannot identify the potentially “active” genes that might drive a gene set-based association. To address these issues, we have developed Gene set analysis Association Using Sparse Signals (GAUSS), a method for gene set association analysis that requires only GWAS summary statistics. For each significantly associated gene set, GAUSS identifies the subset of genes that have the maximal evidence of association and can best account for the gene set association. Using pre-computed correlation structure among test statistics from a reference panel, our p value calculation is substantially faster than other permutation- or simulation-based approaches. In simulations with varying proportions of causal genes, we find that GAUSS effectively controls type 1 error rate and has greater power than several existing methods, particularly when a small proportion of genes account for the gene set signal. Using GAUSS, we analyzed UK Biobank GWAS summary statistics for 10,679 gene sets and 1,403 binary phenotypes. We found that GAUSS is scalable and identified 13,466 phenotype and gene set association pairs. Within these gene sets, we identify an average of 17.2 (max = 405) genes that underlie these gene set associations.

PMID:33730541 | DOI:10.1016/j.ajhg.2021.02.016

Expert Rev Med Devices. 2021 Mar 17. doi: 10.1080/17434440.2021.1905518. Online ahead of print.

ABSTRACT

Purpose: To evaluate the agreement of different biometric parameters obtained using intraoperative spectral-domain optical coherence tomography (SD-OCT) and two swept-source optical coherence tomography (SS-OCT) based-biometers.Methods: 102 eyes were assessed using the intraoperative SD-OCT integrated into the Catalys femtosecond-laser, and the IOLMaster 700 and Anterion SS-OCT-based-biometers. Central corneal thickness (CCT), anterior chamber depth (ACD), white-to-white (WTW), and lens thickness (LT) were measured.Results: There were statistically significant differences for CCT, ACD, WTW and LT between devices (p<0.001). The mean difference for ACD ranged from -0.067 to -0.250 mm, with the largest mean difference being between the IOLMaster 700 and Catalys. CCT mean differences ranged from 7 to 32 µm, with the largest mean difference being between the Anterion and Catalys. For WTW, the comparison between the IOLMaster 700 vs Catalys showed the largest mean difference (0.38 mm). However, the mean differences for LT from all three devices were quite similar, ranging from -0.02 to -0.08 mm.Conclusions: SS-OCT biometers showed good agreement for ACD, CCT, WTW and LT. The SD-OCT showed ACD, CCT and WTW values that do not seem to be interchangeable with the SS-OCT biometers, however, this device did show excellent agreement in the case of LT.

PMID:33730515 | DOI:10.1080/17434440.2021.1905518

Hepatology. 2021 Mar 17. doi: 10.1002/hep.31809. Online ahead of print.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome (HELIX) cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α). Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSION: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

PMID:33730435 | DOI:10.1002/hep.31809

Eur J Neurol. 2021 Mar 17. doi: 10.1111/ene.14828. Online ahead of print.

ABSTRACT

BACKGROUND: Monoclonal antibodies targeting CGRP or its receptor (anti-CGRP mAbs) are proven to be effective treatments in migraine prevention. Real-world evidence studies assessing their efficacy are scarce.

METHODS: Our objective was to assess the efficacy of anti-CGRP mAbs in our clinical cohort resistant to onabotulinumtoxinA. We prospectively analyzed ≥50% response rate in patients who initiated treatment with anti-CGRP mAbs and who were partial or non-responders to onabotulinumtoxinA.

RESULTS: 155 patients completed treatment with anti-CGRP mAbs at 3-month of follow-up. No statistically significant differences were found in ≥50% response in headache frequency in patients with prior onabotulimuntoxinA treatment partial or complete failure. Regarding dual therapy with onabotulinumtoxinA and anti-CGRP mAbs, no statistically significant differences were found in ≥50% response in headache frequency between monotherapy or dual therapy.

CONCLUSIONS: Patients with prior treatment failure or partial efficacy to onabotulinumtoxinA respond to anti-CGRP mAbs. After 3 months, in our cohort, dual therapy does not seem to add more benefit than anti-CGRP mAbs in monotherapy.

PMID:33730441 | DOI:10.1111/ene.14828

Vet Ophthalmol. 2021 Mar 17. doi: 10.1111/vop.12883. Online ahead of print.

ABSTRACT

PURPOSE: To compare cataract characteristics and complications related to cataracts and phacoemulsification in the Siberian Husky (Huskies) versus other canine breeds (non-Huskies).

ANIMALS: A total of 50 Huskies (92 eyes) and 96 non-Huskies (182 eyes) were evaluated.

METHODS: Medical records of Huskies (at four university veterinary hospitals, 2008-2018) and non-Huskies (Colorado State University, 2017-2018) diagnosed with cataracts were reviewed. Age of dog, cataract stage at presentation, and pre- and post-operative complications were recorded and analyzed.

RESULTS: Mean (±standard deviation) age at presentation was significantly lower in Huskies (3.5 ± 3.3 years) compared to non-Huskies (9.5 ± 2.9 years) (p < .0001). Huskies more commonly presented with hereditary cataracts than non-Huskies (84% versus 52%) and a significantly higher percentage of non-Huskies presented with diabetic cataracts than Huskies (48% versus 16%; p = .0001). Cataract stage at presentation did not differ between Huskies and non-Huskies. Phacoemulsification was performed in 40% (20 out of 50 dogs, 39 out of 92 eyes) of Huskies and 42% (40 out of 96 dogs, 74 out of 182 eyes) of non-Huskies. Pre-operative and post-operative retinal detachment were more common in Huskies than non-Huskies (13% versus 2% and 10% versus 1%, respectively) but the difference was not significant. Other post-operative complications occurred with similar frequency in both groups (p ≥ .17).

CONCLUSIONS: Huskies evaluated for cataracts were younger and less likely to present with diabetic cataracts than other canine breeds and, although not statistically significant, had a clinically important increased risk of retinal detachment pre- and post-phacoemulsification.

PMID:33730445 | DOI:10.1111/vop.12883

Acad Emerg Med. 2021 Mar 17. doi: 10.1111/acem.14252. Online ahead of print.

ABSTRACT

OBJECTIVE: Firearm injuries are one of the leading preventable causes of morbidity and mortality among children. Limited information exists about the impact of non-fatal firearm injuries on utilization and expenditures. Our objective was to compare healthcare encounters and expenditures one year before and one year following a non-fatal firearm injury.

METHODS: Retrospective cohort study of children 0-18 years with ICD-9/ICD-10 diagnosis codes for firearm injury in the emergency department or inpatient setting from 2010-2016 in the Medicaid MarketScan claims database. Outcomes included: 1) difference in healthcare encounters for one year before and one year after injury; 2) difference in healthcare expenditures; 3) difference in complex chronic disease status. Descriptive statistics characterized patient demographics and healthcare utilization. Health expenditures were evaluated with Wilcoxon Sign Rank Tests.

RESULTS: Among 3,296 children, there were 47,660 healthcare encounters before the injury and 61,660 after. Concomitantly, there was an overall increase of $18.5 million in health expenditures ($5,612 per patient). There was a 40% increase in children qualifying for complex chronic condition status after firearm injury.

CONCLUSIONS: Children who experience non-fatal firearm injury have increased number of healthcare encounters, chronic disease classification, and healthcare expenditures in the year following the injury. Prevention of firearm injuries in this vulnerable age group may result in considerable reductions in morbidity and healthcare costs.

PMID:33730446 | DOI:10.1111/acem.14252

J Oral Pathol Med. 2021 Mar 17. doi: 10.1111/jop.13170. Online ahead of print.

ABSTRACT

BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory condition with an undefined malignant transformation potential. There have been many attempts at providing a specific definition of OLP without conclusive outcomes. A new set of diagnostic criteria was proposed in 2016 by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in an endeavour to resolve this issue, and this has not yet been evaluated. This study aimed to assess the utility of AAOMP proposed criteria for the diagnosis of OLP.

METHODS: Five pathologists blindly assessed a cohort of 215 digital whole slide images (WSI) obtained from haematoxylin and eosin stained microscopic slides. Forty-six WSI were included twice to assess the intra-observer agreement. Included cases were diagnosed clinically as either OLP or oral lichenoid reaction. Each pathologist was asked to utilize the AAOMP histopathological criteria while assessing slides. The variations in diagnoses were assessed by unweighted kappa statistics.

RESULTS: The level of intra-observer agreement was very good (0.801 to 0.899). The level of inter-observer agreement among the observers varied from good (0.658) to very good (0.842) when the responses were categorized as evident/compatible OLP versus no OLP, and was good (0.62 to 0.725) when the responses were categorized as evident OLP, versus compatible OLP, versus no OLP. The clinico-pathological correlation was 87.6%.

CONCLUSION: A reliable level of agreement can be achieved by pathologists for the diagnosis of OLP using the AAOMP criteria for differentiation between lichenoid and other conditions. There are still limitations in discriminating OLP from oral lichenoid lesions microscopically.

PMID:33730381 | DOI:10.1111/jop.13170

J Appl Behav Anal. 2021 Mar 17. doi: 10.1002/jaba.823. Online ahead of print.

ABSTRACT

Although in-vivo behavioral skills training (BST) is often effective, it may be too resource-intensive for organizations that rely on volunteers. Alternatives to in-vivo BST include video models or interactive computer training (ICT), but the utility of these procedures for training volunteers remains largely unknown. We used a randomized control trial to teach multiple skills to new volunteers at a therapeutic riding center. A total of 60 volunteers were assigned to one of three groups using block randomization. Depending on group assignment, volunteers received instructions and modeling through in-vivo interactions, a video model, or ICT. All volunteers completed in-vivo role plays with feedback. Skills were measured by unblinded observers during role plays. There were no statistically significant differences in accuracy of role-play performance between volunteers in the in-vivo BST and ICT groups, but both outperformed the video-model group. The ICT and video model required statistically significantly less time from a live instructor than did in-vivo training. Thus, although in-vivo BST remains best practice, ICT may be a viable alternative when training resources are limited.

PMID:33730397 | DOI:10.1002/jaba.823

Int J Paediatr Dent. 2021 Mar 17. doi: 10.1111/ipd.12781. Online ahead of print.

ABSTRACT

BACKGROUND: The number of child abuse cases is increasing worldwide therefore it is important to educate individuals having contact with children about it. This includes dentists who play a pivotal role in detecting and reporting these cases.

AIM: To identify and compare the final year dental student’s knowledge, attitudes and practice in relation to child abuse.

DESIGN: A 38-item and four part online questionnaire was distributed to students of 11 dental schools in 10 countries. SPSS and GraphPad Prism were used for data analysis. The levels of statistical significance were determined using a chi-square test. P ≤ 0.05 was considered to be statistically significant.

RESULTS: A total of 660 students completed the survey. Fifty-six percent of the students received formal training on child abuse, and 86% wanted additional training. The knowledge of child abuse was significantly higher in Australia, USA and Jordan compared to other countries. The internet (60.3%) was widely used as an information source for child abuse.

CONCLUSIONS: The study showed that dental students lack knowledge and experience in recognising and reporting child abuse. Most respondents indicated a desire for additional training, therefore dental schools should review what they are currently teaching and make changes as appropriate.

PMID:33730406 | DOI:10.1111/ipd.12781