Category: Statistics

Adv Med Sci. 2021 Mar 14;66(1):215-220. doi: 10.1016/j.advms.2021.03.002. Online ahead of print.

ABSTRACT

PURPOSE: The long-term clinical outcome of adjuvant stereotactic radiotherapy (SRT) in neovascular age-related macular degeneration (nAMD) patients was evaluated.

METHODS: This case-control study included patients with unilateral nAMD, who underwent SRT complementary to standard anti-VEGF treatment. Only patients with monthly follow-up over at least three years were considered. Number of intravitreal injections, visual acuity (VA), central retinal thickness (CRT), and subfoveal choroidal thickness (SFCT) were evaluated and compared to baseline as well as to an age- and gender-matched control group, who received anti-VEGF monotherapy.

RESULTS: Twenty patients were irradiated and had complete follow-up. Cumulatively, SRT patients needed significantly less injections than non-irradiated ones over three years (14 vs. 18, p ​= ​0.014), while median VA did not show statistically significant changes (0.4 logMAR at baseline to 0.65 logMAR at final follow-up, p ​= ​0.061). CRT remained steady, but SFCT showed a continuous thinning of almost 50 ​μm (p ​= ​0.031) in irradiated patients over three years. Multiple linear regression analysis revealed that SFCT and VA at time of irradiation are significant prognostic factors of VA change in SRT patients over the following three years (F(2,17) ​= ​23.946, p<0.001, R² of 0.738).

CONCLUSIONS: SRT significantly reduced the cumulative anti-VEGF treatment burden over three years, however, this was mainly driven by the results of the first year after irradiation. A thinner SFCT at time of irradiation was associated with poorer visual outcome. While further research and investigation are warranted to elucidate the underlying pathogenesis, SFCT could be a potential biomarker when evaluating a patient’s suitability for SRT.

PMID:33730635 | DOI:10.1016/j.advms.2021.03.002

Lung Cancer. 2021 Feb 19;155:53-60. doi: 10.1016/j.lungcan.2021.02.021. Online ahead of print.

ABSTRACT

OBJECTIVES: This post hoc analysis assessed the safety of pemetrexed and platinum in combination with pembrolizumab, including time-to-onset and time-to-resolution of all-cause any-grade and grade ≥3 adverse events (AEs) and renal AEs.

MATERIALS AND METHODS: Patient-level data from KEYNOTE-189 were analyzed in the all-subjects-as-treated population (pembrolizumab arm, n = 405; placebo arm, n = 202), and among patients who received ≥5 cycles of pemetrexed (pemetrexed/pembrolizumab/platinum arm, n = 310; pemetrexed/placebo/platinum arm, n = 135). All-cause AEs were selected based on ≥2 % incidence from previously reported KEYNOTE-189 data and included neutropenia, febrile neutropenia, anemia, thrombocytopenia, asthenia, fatigue, dyspnea, diarrhea, nausea, vomiting, pneumonitis, and renal events. Descriptive statistics summarized all-cause AEs. Medians and interquartile ranges were used to examine time-to-onset and time-to-resolution. The data cutoff was November 8, 2017.

RESULTS: In both treatment arms, most non-hematologic (nausea, vomiting, diarrhea, and asthenia), and hematologic (febrile neutropenia, thrombocytopenia, and neutropenia) grade ≥3 AEs with ≥2 % incidence had a median time-to-onset within the first 4 cycles, and a median time-to-resolution of within 2 weeks from onset. A small number of AEs had longer median time-to-onset (pneumonitis and fatigue) and median time-to-resolution (pneumonitis, fatigue, acute kidney injury, and anemia). Among patients who received ≥5 cycles of pemetrexed, the incidence of any-grade renal toxicity in the pemetrexed/pembrolizumab/platinum arm was 2.3 % in Cycles 1-4, 4.8 % in Cycles 5-8, 2.6 % in Cycles 9-12, and 2.5 % in Cycles ≥13; and, in the pemetrexed/placebo/platinum arm, 0.7 % in Cycles 1-4, 1.5 % in Cycles 5-8, 1.3 % in Cycles 9-12, and 2.0 % in Cycles ≥13.

CONCLUSION: Pemetrexed/pembrolizumab/platinum has manageable toxicity with longer duration of treatment. While the incidence of renal toxicity was slightly higher in the pembrolizumab combination as compared to pemetrexed, the incidence did not increase in later treatment cycles. These results support the safe use of the KEYNOTE-189 regimen in clinical practice.

CLINICAL TRIAL REGISTRATION NUMBER: NCT02578680 (clinicaltrials.gov).

PMID:33730652 | DOI:10.1016/j.lungcan.2021.02.021

J Stroke Cerebrovasc Dis. 2021 Mar 14;30(5):105672. doi: 10.1016/j.jstrokecerebrovasdis.2021.105672. Online ahead of print.

ABSTRACT

OBJECTIVES: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers.

MATERIALS AND METHODS: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM).

RESULTS: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%).

CONCLUSIONS: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.

PMID:33730599 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105672

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

Ultrasonics. 2021 Mar 4;114:106411. doi: 10.1016/j.ultras.2021.106411. Online ahead of print.

ABSTRACT

This study investigated the application of dual-frequency type dynamic acoustic fields for size-selective particle separation on centimeter scale in a continuous flow. The 3D-printed X-shaped prototype has two inlets and two outlets. The dynamic acoustic field is generated by two transducers positioned under an angle of 60^° and operating at slightly different frequencies. The acoustic reflections are eliminated by placing sound-absorbing material inside the prototype and the non-resonant operation is confirmed by the electrical admittance measurements. Numerical calculations suggested that pressure generated by each transducer does not need to have equal amplitude. Computer simulations and lab experiments were carried out for different frequency differences and flow rates. The results demonstrated the ability of dual-frequency dynamic acoustic fields for size-selective particle filtration on centimeter scale, with a total flow rate up to.1Lh^-1.

PMID:33730595 | DOI:10.1016/j.ultras.2021.106411

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