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Nevin Manimala Statistics

Visual mapping of body image disturbance in anorexia nervosa reveals objective markers of illness severity

Sci Rep. 2021 Jun 10;11(1):12262. doi: 10.1038/s41598-021-90739-w.

ABSTRACT

Body image disturbance (BID) is a core feature of eating disorders, for which there are few objective markers. We examined the feasibility of a novel digital tool, “Somatomap”, to index BID related to anorexia nervosa (AN) severity. Fifty-five AN inpatients and 55 healthy comparisons (HC) outlined their body concerns on a 2-Dimensional avatar. Next, they indicated sizes/shapes of body parts for their current and ideal body using sliders on a 3-Dimensional avatar. Physical measurements of corresponding body parts, in cm, were collected for reference. We evaluated regional differences in BID using proportional z-scores to generate statistical body maps, and multivariate analysis of covariance to assess perceptual discrepancies for current body, ideal body, and body dissatisfaction. The AN group demonstrated greater regional perceptual inaccuracy for their current body than HC, greater discrepancies between their current and ideal body, and higher body dissatisfaction than HCs. AN body concerns localized disproportionately to the chest and lower abdomen. The number of body concerns and perceptual inaccuracy for individual body parts was strongly associated with Eating Disorder Examination Questionnaire (Global EDE-Q) scores across both groups. Somatomap demonstrated feasibility to capture multidimensional aspects of BID. Several implicit measures were significantly associated with illness severity, suggesting potential utility for identifying objective BID markers.

PMID:34112818 | DOI:10.1038/s41598-021-90739-w

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The treatment of neurogenic lower urinary tract dysfunction in persons with spinal cord injury: An open label, pilot study of anticholinergic agent vs. mirabegron to evaluate cognitive impact and efficacy

Spinal Cord Ser Cases. 2021 Jun 10;7(1):50. doi: 10.1038/s41394-021-00413-6.

ABSTRACT

STUDY DESIGN: Pre-post intervention.

OBJECTIVES: 1. To test whether replacement of oral anticholinergic (AC) agents with mirabegron for neurogenic lower urinary tract dysfunction (NLUTD) yields improved cognitive function in older persons with spinal cord injury (SCI). 2. To test whether mirabegron is safe and as efficacious as AC.

SETTING: USA.

METHODS: Pilot study: Twenty older (>60 y/o) persons with SCI taking chronic (>6 months) AC medication for NLUTD were enrolled. All participants were first studied on AC at baseline then switched to mirabegron for 6 months. Primary outcomes were cognitive tests of (1) executive function (TEXAS, SDMT); (2) attention (SCWT); and (3) memory (SLUMS and WMS-IV Story A/B). Secondary outcomes assessed efficacy and safety including Neurogenic Bladder Symptom Score (NBSS), bladder diary, neurogenic bowel dysfunction (NBD) survey, heart rate (HR), electrocardiogram (EKG), and mean arterial pressure (MAP).

RESULTS: When switching from AC to mirabegron for NLUTD, older persons with SCI exhibited statistically significant improvements in immediate Story A recall (p = 0.01), delayed story A and B recall (p = 0.01, 0.004), and in TEXAS (p = 0.04). Three subscores within NBSS significantly improved (p = 0.001) and the frequency of incontinence decreased (p = 0.03) on mirabegron. NBD, HR, MAP, and EKGs were unchanged.

CONCLUSIONS: Older persons with SCI on AC for NLUTD demonstrated improved short-term and delayed memory (WMS-IV Story A/B) as well as executive function (TEXAS) when switched to mirabegron. Efficacy of mirabegron for NLUTD symptoms was superior to AC with no adverse effects on bowel or cardiovascular function.

SPONSORSHIP: Claude D. Pepper Older Americans Independence Center.

PMID:34112758 | DOI:10.1038/s41394-021-00413-6

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Nevin Manimala Statistics

Rapid detection of identity-by-descent tracts for mega-scale datasets

Nat Commun. 2021 Jun 10;12(1):3546. doi: 10.1038/s41467-021-22910-w.

ABSTRACT

The ability to identify segments of genomes identical-by-descent (IBD) is a part of standard workflows in both statistical and population genetics. However, traditional methods for finding local IBD across all pairs of individuals scale poorly leading to a lack of adoption in very large-scale datasets. Here, we present iLASH, an algorithm based on similarity detection techniques that shows equal or improved accuracy in simulations compared to current leading methods and speeds up analysis by several orders of magnitude on genomic datasets, making IBD estimation tractable for millions of individuals. We apply iLASH to the PAGE dataset of ~52,000 multi-ethnic participants, including several founder populations with elevated IBD sharing, identifying IBD segments in ~3 minutes per chromosome compared to over 6 days for a state-of-the-art algorithm. iLASH enables efficient analysis of very large-scale datasets, as we demonstrate by computing IBD across the UK Biobank (~500,000 individuals), detecting 12.9 billion pairwise connections.

PMID:34112768 | DOI:10.1038/s41467-021-22910-w

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Nevin Manimala Statistics

Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL

RMD Open. 2021 Jun;7(2):e001662. doi: 10.1136/rmdopen-2021-001662.

ABSTRACT

OBJECTIVES: Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.

METHODS: 15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.

RESULTS: Disease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.

CONCLUSIONS: TCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.

PMID:34112702 | DOI:10.1136/rmdopen-2021-001662

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Sulindac, a non-selective NSAID, reduces breast density in postmenopausal women with breast cancer treated with aromatase inhibitors

Clin Cancer Res. 2021 Jun 10:clincanres.0732.2021. doi: 10.1158/1078-0432.CCR-21-0732. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of sulindac, a non-selective anti-inflammatory drug, for activity to reduce breast density (BD), a risk factor for breast cancer.

EXPERIMENTAL DESIGN: An open-label Phase 2 study was conducted to test the effect of 12 months’ daily sulindac at 150 mg bid on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by non-contrast MRI and reported as change in MRI percent BD (MRPD). A non-randomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12-months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated (SHG) microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy.

RESULTS: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% (95% CI, -14.6 to -4.7) at 12 months; an absolute decrease of -1.4% (95% CI, -2.5 to -0.3). A significant decrease in mean breast tissue collagen fiber straightness (p=0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI only observation group (N = 40).

CONCLUSIONS: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

PMID:34112707 | DOI:10.1158/1078-0432.CCR-21-0732

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Pyrotinib treatment in patients with HER2-positive metastatic breast cancer and brain metastasis: exploratory final analysis of real-world, multicenter data

Clin Cancer Res. 2021 Jun 10:clincanres.0474.2021. doi: 10.1158/1078-0432.CCR-21-0474. Online ahead of print.

ABSTRACT

PURPOSE: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.

EXPERIMENTAL DESIGN: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.

RESULTS: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).

CONCLUSION: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

PMID:34112711 | DOI:10.1158/1078-0432.CCR-21-0474

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Observation of a prethermal discrete time crystal

Science. 2021 Jun 11;372(6547):1192-1196. doi: 10.1126/science.abg8102.

ABSTRACT

Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion quantum simulator to observe the signatures of a nonequilibrium driven phase without disorder-the prethermal discrete time crystal. Here, the heating problem is circumvented not by disorder-induced many-body localization, but rather by high-frequency driving, which leads to an expansive time window where nonequilibrium phases can emerge. Floquet prethermalization is thus presented as a general strategy for creating, stabilizing, and studying intrinsically out-of-equilibrium phases of matter.

PMID:34112691 | DOI:10.1126/science.abg8102

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Initiation of Long-Acting Reversible Contraception in Hospitalized Adolescents in the United States

Hosp Pediatr. 2021 Jun 10:hpeds.2020-001974. doi: 10.1542/hpeds.2020-001974. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze factors associated with the initiation of long-acting reversible contraception (LARC) among adolescent patients in inpatient settings in the United States.

METHODS: This study is a secondary data analysis of the national Kids’ Inpatient Database 2016 data (N = 4200 hospitals). Eligible patients were hospitalized girls 10 to 20 years old. The primary outcome was initiation of LARC (ie, subdermal implant and/or intrauterine device [IUD]) while hospitalized. Covariables included age, race or ethnicity, insurance type, postpregnancy status, geographic region, hospital type (rural or urban), hospital size, and children’s hospital status. Bivariable statistics were calculated by using survey-weighted analysis, and a design-based logistic regression model was used to determine the adjusted odds of LARC initiation and of implant versus IUD initiation.

RESULTS: LARC initiation occurred in 0.4% (n = 3706) of eligible hospital admissions (n = 874 193). There were differences in LARC initiation by patient age, insurance type, race or ethnicity, postpregnancy status, hospital type, and hospital status (all P < .01). In the adjusted model, older age, public insurance, nonwhite race or ethnicity, postpregnancy status, and urban, teaching or larger hospitals were independently associated with LARC initiation (all P < .01). Smaller hospital size and postpregnancy status increased the odds of implant versus IUD initiation after stratifying by hospital region.

CONCLUSIONS: LARC initiation occurred in <1% of adolescent hospitalizations, with 90% of those occurring in postpregnancy adolescents. Addressing LARC capacity in rural, nonteaching, and smaller hospitals is important in increasing access. Future research is needed to identify and close gaps in the number of adolescents desiring and initiating LARC in hospital settings.

PMID:34112700 | DOI:10.1542/hpeds.2020-001974

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Effects of enamel deproteinization with different application times on the shear bond strength of a self-etching primer: An in vitro study

Int Orthod. 2021 Jun 7:S1761-7227(21)00070-X. doi: 10.1016/j.ortho.2021.05.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this in vitro study was to evaluate the effects of enamel deproteinization on the shear bond strength of a self-etching primer Transbond Plus™(TBP), with different application times of sodium hypochlorite (NaOCl 5.25%), primarily and secondarily on the adhesive remnant index score.

MATERIALS AND METHODS: One hundred twenty-five freshly extracted human premolars were randomly and blindly divided into five groups according to the enamel surface preparation, as follows (n=25): group 1(control): Etching with 37% phosphoric acid for 15seconds+Bonding; group 2 (control): TBP™ without NaOCl, group 3: 60seconds NaOCl+TBP™, group 4: 30seconds NaOCl+TBP™, group 5: 15seconds NaOCl+TBP™. The same composite resin was used (Transbond XT™) to bond the orthodontic metal brackets. After the immersion of the teeth in distilled water at 37°C for 24hours the shear bond strength was measured using the universal testing machine and the adhesive remnant index score (ARI) was evaluated under an optical microscope (25×).

RESULTS: The mean SBS values (inMPa) of the groups were respectively: group 1: 13.03±5.36; group 2: 12.28±3.06; group 3: 12.38±4.55; group 4: 12.98±5.76; and group 5: 11.73±5.67. Enamel deproteinization increased the SBS for groups 3 and 4, but no statistically significant difference was found between the five groups (P=0.883). Group 1 showed the highest ARI scores, with 52% of the teeth retaining all the adhesive (score 3). However, for all the other groups, scores 0 and 1 were predominant, with less than half of the adhesive or no adhesive at all remaining on the teeth.

CONCLUSIONS: Enamel deproteinization with sodium hypochlorite (5.25%) and the variation of its application time has no effect on the SBS of the self-etching primer Transbond Plus ™.

PMID:34112607 | DOI:10.1016/j.ortho.2021.05.002

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Evaluation of physiodispenser assisted micro-osteoperforation on the rate of tooth movement and associated periodontal tissue status during individual canine retraction in first premolar extraction cases: A split-mouth randomized controlled clinical trial

J World Fed Orthod. 2021 Jun 7:S2212-4438(21)00020-5. doi: 10.1016/j.ejwf.2021.05.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the rate of tooth movement and the periodontal tissue status over a period of 90 days with and without micro-osteoperforation (MOP).

METHOD: Thirty-three adults of the 19 to 25 age group undergoing labial fixed orthodontic treatment with bilateral maxillary first premolar extraction, requiring individual canine retraction as a part of the treatment plan, were recruited for this split-mouth randomized clinical trial. While performing micro-implant-assisted canine retraction in the maxillary arch, the experimental side received three MOPs each on the mesial and distal aspects of the canine root. The amount of tooth movement was measured clinically at every 15 days interval for 90 days; the periodontal status was assessed clinically (probing depth, relative attachment level) and tomographically (canine root length, alveolar bone level) at the 1st day and 90th day of retraction. The data were subjected to appropriate statistical analyses.

RESULTS: A statistically significant difference in tooth movement on the MOP side was observed in the first 45 days, amounting to 1.5 times more than that of the control side. However, during 45 to 90 days, the difference in the rate of tooth movement between the sides was not statistically significant. Changes in periodontal variables were also insignificant between the sides except for the distal alveolar bone level.

CONCLUSION: An increase in the rate of tooth movement can be achieved without any periodontal adverse effects in the first 45 days of the MOP procedure. The effectiveness of the MOP procedure on the rate of tooth movement gradually declined thereafter.

TRIAL REGISTRATION: CTRI/2019/07/020403.

PMID:34112627 | DOI:10.1016/j.ejwf.2021.05.001