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Nevin Manimala Statistics

Erratum: Randomized Trials of Retosiban versus Placebo or Atosiban in Spontaneous Preterm Labor

Am J Perinatol. 2021 Jul 8. doi: 10.1055/s-0041-1731633. Online ahead of print.

NO ABSTRACT

PMID:34237775 | DOI:10.1055/s-0041-1731633

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Steroids Significantly Decrease Postoperative Postural Hypotension in Total Knee Replacement

J Knee Surg. 2021 Jul 8. doi: 10.1055/s-0041-1731722. Online ahead of print.

ABSTRACT

Total knee replacement (TKR) is one of the most common orthopaedic procedures performed, and enhanced recovery after surgery (ERAS) has been developed and incorporated into inpatient surgical pathways to improve patient outcomes. Under ERAS recommendations, multimodal prophylaxis has been used to help manage postoperative nausea and vomiting (PONV) following TKR. Dexamethasone is one of the commonly used for this and the anti-inflammatory properties could depress vagal activity, reducing postural hypotension (PH). The hypothesis of this study is that postoperative dexamethasone use is associated with lower rates of early postoperative PH following TKR surgery. In our institution, patients who undergo elective primary TKR are admitted on the day of surgery and follow a standardized ERAS protocol. Data on patients who underwent elective primary TKR under a single adult reconstruction team from September 2017 to March 2020 were reviewed and analyzed. A review of demographic characteristics, surgical data, postoperative medications, and postoperative notes was performed. Binary logistic regression was used to assess the effect of the use of dexamethasone on PH, with an adjusted odds ratio (OR) calculated after accounting for potential confounders. Of the 149 patients were included in the study, 78 had dexamethasone postoperatively, and 71 did not. Patients who had received dexamethasone were statistically less likely to suffer from PH (OR = 0.31, p = 0.03) and less likely to develop PONV (OR = 0.21, p = 0.006). Patients who had received dexamethasone were more likely able to participate in early physiotherapy (OR = 2.42, p = 0.14), and this result was statistically insignificant. The use of postoperative intravenous dexamethasone is significantly associated with lower rates of postoperative PH after TKR. However, more studies are required to assess the optimal dosing amount and frequency, as well as to assess other factors which can enhance early postoperative patient mobilization as part of our goals for ERAS. This therapeutic study reflects level of evidence III.

PMID:34237779 | DOI:10.1055/s-0041-1731722

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Collocation based training of neural ordinary differential equations

Stat Appl Genet Mol Biol. 2021 Jul 8. doi: 10.1515/sagmb-2020-0025. Online ahead of print.

ABSTRACT

The predictive power of machine learning models often exceeds that of mechanistic modeling approaches. However, the interpretability of purely data-driven models, without any mechanistic basis is often complicated, and predictive power by itself can be a poor metric by which we might want to judge different methods. In this work, we focus on the relatively new modeling techniques of neural ordinary differential equations. We discuss how they relate to machine learning and mechanistic models, with the potential to narrow the gulf between these two frameworks: they constitute a class of hybrid model that integrates ideas from data-driven and dynamical systems approaches. Training neural ODEs as representations of dynamical systems data has its own specific demands, and we here propose a collocation scheme as a fast and efficient training strategy. This alleviates the need for costly ODE solvers. We illustrate the advantages that collocation approaches offer, as well as their robustness to qualitative features of a dynamical system, and the quantity and quality of observational data. We focus on systems that exemplify some of the hallmarks of complex dynamical systems encountered in systems biology, and we map out how these methods can be used in the analysis of mathematical models of cellular and physiological processes.

PMID:34237805 | DOI:10.1515/sagmb-2020-0025

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Serum Levels of Soluble Receptor for Advanced Glycation End Products Are Reduced in Euthyroid Children with Newly Diagnosed Hashimoto’s Thyroiditis: A Pilot Study

Horm Res Paediatr. 2021 Jul 8:1-7. doi: 10.1159/000517341. Online ahead of print.

ABSTRACT

OBJECTIVE: No data are available on advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in pediatric patients with Hashimoto’s thyroiditis (HT). The present study was aimed to simultaneously evaluate serum levels of sRAGE, AGEs, and advanced oxidation protein products (AOPPs) and investigate the relationships between these oxidative stress markers and clinical and biochemical parameters of thyroid function in euthyroid children with HT.

DESIGN: This is a case-control study carried out in a single university hospital center.

METHODS: We enrolled 19 newly diagnosed euthyroid HT pediatric patients (3 M, 16 F; median age 12.44 years, range 6.54-15.81 years) and 16 age-, sex-, and BMI-matched healthy controls (5 M, 11 F; median age 12.83 years, range 5.68-15.07 years). None was on levothyroxine treatment. The exclusion criteria were autoimmune, inflammatory, and infection comorbidities. Patients did not differ significantly from controls with regard to lipid or for anthropometric parameters.

RESULTS: sRAGE levels were significantly lower in HT patients (median 414.30 pg/mL, range 307.30-850.30 pg/mL) than in controls (561.30, 273.20-1121.60 pg/mL; p = 0.034). No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98-186.72 vs. 133.90, 94.06-200.78 AU/g prot, p = 0.707) and AOPPs (1.13 nmol/mL, 0.62-1.83 vs. 1.17, 0.76-1.42 nmol/mL, p = 0.545).

CONCLUSIONS: sRAGE levels were decreased in euthyroid children/adolescents at the onset of HT, suggesting that autoimmunity per se seems to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.

PMID:34237741 | DOI:10.1159/000517341

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Characteristics Associated With Treatment Failure 1 Year After Midurethral Sling in Women With Mixed Urinary Incontinence

Obstet Gynecol. 2021 Jul 8. doi: 10.1097/AOG.0000000000004444. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate characteristics associated with treatment failure 1 year after midurethral sling in women with mixed urinary incontinence.

METHODS: Four-hundred three women who participated in a randomized trial that compared midurethral sling and behavioral and pelvic floor muscle therapy (combined group) compared with midurethral sling alone for mixed incontinence with 1-year follow-up data were eligible for this planned secondary analysis. Overall treatment failure was defined as meeting criteria for subjective or objective failure or both. Subjective failure was defined as not meeting the minimal clinical important difference for improvement on the UDI (Urogenital Distress Inventory) total score (26.1 points). Objective failure was defined as not achieving 70% improvement on mean incontinence episodes of any type per day or having undergone any additional treatment for persistent urinary symptoms at 12 months postoperative. Logistic regression models for treatment failure were constructed. Independent variables included site and treatment group, and clinical and demographic variables based on bivariate comparisons (P<.2). Treatment group interaction effects were evaluated.

RESULTS: One hundred twelve of 379 (29.6%) women had overall treatment failure, with 56 of 379 (14.7%) undergoing additional treatment but only two needing intervention for stress incontinence. Previous overactive bladder (OAB) medication (unadjusted odds ratio [OR] 2.19, adjusted odds ratio [aOR] 1.96, 95% CI 1.17-3.31); detrusor overactivity on cystometrogram (OR 2.25, aOR 2.82, 95% CI 1.60-4.97); and higher volume at first urge (OR 1.03, aOR 1.04, 95% CI 1.01-1.07) were associated with overall failure. Worse UDI-urgency scores were associated with failure, with an added interaction effect in the midurethral sling-alone group.

CONCLUSIONS: Certain clinical and urodynamic variables are associated with treatment failure after midurethral sling in women with mixed urinary incontinence. Women with more severe urgency symptoms at baseline may benefit from perioperative behavioral and pelvic floor muscle therapy combined with midurethral sling. Overall, the need for additional urinary treatment was low and primarily for OAB.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959347.

PMID:34237755 | DOI:10.1097/AOG.0000000000004444

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DNA methylation biomarkers for diagnosis of primary liver cancer and distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma

Aging (Albany NY). 2021 Jul 8;13(undefined). doi: 10.18632/aging.203249. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.

PMID:34237708 | DOI:10.18632/aging.203249

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Spatio-temporal equalization multi-window algorithm for asynchronous SSVEP-based BCI

J Neural Eng. 2021 Jul 8. doi: 10.1088/1741-2552/ac127f. Online ahead of print.

ABSTRACT

OBJECTIVE: Asynchronous brain-computer interfaces (BCIs) show significant advantages in many practical application scenarios. Compared with the rapid development of synchronous BCIs technology, the progress of asynchronous BCI research, in terms of containing multiple targets and training-free detection, is still relatively slow. In order to improve the practicability of the brain-computer interface, a spatio-temporal equalization multi-window algorithm (STE-MW) was proposed for asynchronous detection of steady-state visual evoked potential (SSVEP) without the need for acquiring calibration data.

APPROACH: The algorithm used spatio-temporal equalization strategy to intercept EEG signals of different lengths through multiple stacked time windows and statistical decisions-making based on Bayesian risk decision-making. Different from the traditional asynchronous algorithms based on the “non-control state detection” methods, this algorithm was based on the “statistical inspection-rejection decision” mode and did not require a separate classification of non-control states, so it can be effectively applied to detections for large-scale candidates.

MAIN RESULTS: Online experimental results involving fourteen healthy subjects showed that, in the continuously input experiments of 40 targets, the algorithm achieved the average recognition accuracy of 97.2%±2.6% and the average information transfer rate of 106.3±32.0 bits/min. At the same time, the average false alarm rate in the 240-seconds resting state test was 0.607±0.602 min^(-1). In the free spelling experiments involving patients with severe amyotrophic lateral sclerosis, the subjects achieved an accuracy of 92.7% and an average information transfer rate of 43.65 bits/min in two free spelling experiments.

SIGNIFICANCE: This algorithm can achieve high-performance, high-precision, and asynchronous detection of SSVEP signals with low algorithm complexity and false alarm rate under multi-targets and training-free conditions, which is helpful for the development of asynchronous BCI systems.

PMID:34237711 | DOI:10.1088/1741-2552/ac127f

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An Atlas-guided automatic planning approach for rectal cancer intensity-modulated radiotherapy

Phys Med Biol. 2021 Jul 8. doi: 10.1088/1361-6560/ac127d. Online ahead of print.

ABSTRACT

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing, and plan fine-tuning modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The beam morphing function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the plan fine-tuning function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms of V100%(p=0.76) and homogeneity index (HI)(p=0.073), respectively. The CI index showed they had a statistically significant difference. but the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1cGy (p<0.05) and V50 by 0.9% (p<0.05), and slightly increased the left and right femoral head mean dose by 70.1cGy (p<0.05) and 69.7cGy (p<0.05), respectively. This work developed an efficient and automatic approach that could fully automate the IMRT planning process in rectal cancer radiotherapy. It reduced the plan quality dependence on the planner experience and maintained the comparable plan quality with P-auto plans.

PMID:34237715 | DOI:10.1088/1361-6560/ac127d

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Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study

Eur Neuropsychopharmacol. 2021 Jul 5;52:18-30. doi: 10.1016/j.euroneuro.2021.06.003. Online ahead of print.

ABSTRACT

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen’s d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

PMID:34237655 | DOI:10.1016/j.euroneuro.2021.06.003

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A systematic review and meta-analysis of observational studies on the association between animal protein sources and risk of rheumatoid arthritis

Clin Nutr. 2021 Jun 5;40(7):4644-4652. doi: 10.1016/j.clnu.2021.05.026. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the linear and nonlinear dose-response associations of animal-based dietary protein intake and risk of developing rheumatoid arthritis (RA).

METHODS: A systematic search of MEDLINE, Scopus and Embase was conducted up to October 2020. Observational studies that report risk estimates of RA for animal-based protein consumption were included. We calculated pooled relative risks (RRs) by using a random-effects model. Linear and non-linear dose-response analyses were performed to examine the dose-response relations between animal-based protein consumption and RA.

RESULTS: Seven cohort studies (n = 457,554) with 3545 incident cases and six case-control studies with 3994 cases and 5252 controls were identified. Highest compared with the lowest category of fish consumption was inversely associated with risk of RA (RR: 0.89; 95% CI, 0.80 to 0.99; I2 = 0%, n = 10). Also, a 100 g/day increment in fish intake was associated with a 15% decreased risk of RA. Dose-response analysis showed a modest U-shaped association between fish consumption and incidence of RA, with the lowest risk at a fish intake of 20-30 g/day (Pnon-linearity = 0.04). We found no significant association between consumption of red meat, poultry or dairy and the risk of RA.

CONCLUSION: The present study revealed a significant reverse association between fish consumption and risk of RA. While we observed no association between red meat, dairy or poultry consumption and risk of RA. Further well-designed prospective studies are needed to support our findings.

PMID:34237693 | DOI:10.1016/j.clnu.2021.05.026