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Nevin Manimala Statistics

Urinary arsenic and relative telomere length in 5-7 year old children in Bangladesh

Environ Int. 2021 Jul 14;156:106765. doi: 10.1016/j.envint.2021.106765. Online ahead of print.

ABSTRACT

BACKGROUND: Telomere length has been associated with the occurrence and progression of common chronic and age-related diseases, and in younger populations, may represent a biomarker of disease susceptibility. Early childhood is a critical period for telomere biology as this period is characterized by a rapid decline in telomere length due to a large turnover of highly proliferative cells and may represent a period of unique sensitivity to environmental insults. Arsenic (As) exposure has been associated with both telomere lengthening and shortening in adults and children and some evidence suggests the effects may differ by level and timing of exposure.

OBJECTIVES: Given the lack of clarity across studies, we investigated the association between urinary As and leukocyte telomere length among 476 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children’s Health (BiRCH) cohort.

METHODS: In a series of multivariable models, adjusted for key covariates, we examined associations between urinary As and relative telomere length (RTL) of whole blood DNA.

RESULTS: We observed small but consistent, negative associations between urinary As and RTL, such that a doubling of urinary As was associated with a -0.017 (95% CI: -0.030, -0.005; p = 0.0056) decrease in RTL, in fully adjusted models. We also observed a somewhat stronger inverse relationship between urinary As concentration and RTL among children born to fathers ≥ 30 years of age at the time of birth, than those < 30 years; however, we did not observe a statistically significant interaction.

DISCUSSION: Our study suggests that As influences RTL, with detectable associations in early to mid-childhood. Further studies are needed to confirm our findings and investigate the potential long-term impacts of telomere shortening in childhood on later life health outcomes. Additional studies exploring how dose and timing of exposure may relate to RTL are critical to understanding As’s relationship to telomere length.

PMID:34273872 | DOI:10.1016/j.envint.2021.106765

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Nevin Manimala Statistics

Five spectrophotometric methods for simultaneous determination of Amlodipine besylate and celecoxib in presence of its toxic impurity

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 2;263:120137. doi: 10.1016/j.saa.2021.120137. Online ahead of print.

ABSTRACT

Five simple, selective and accurate spectrophotometric methods have been applied and developed for first time for simultaneous determination of amlodipine besylate (AML) and celecoxib (CEL) in presence of one harmful impurity, 4-methylacetophenone (MAP), in their ternary mixture without prior separation. Those spectrophotometric methods were developed and called: dual wave length in ratio spectra (DWRS), successive ratio-derivative spectra (SDR), modified absorption factor method (MAFM), modified amplitude center method (MACM) and first derivative -zero crossing coupled with amplitude factor method (FDAF). These methods include various steps using zero /or ratio /or derivative spectra and some mathematical techniques. Linear calibration curves were constructed over the concentration range of 2-100, 10-200 and 0.5-20 µg/mL for AML, CEL and MAP, respectively. High sensitivity with low LOD values 0.583, 3.118 and 0.147 for AML, CEL and MAP, respectively were obtained. Moreover, validation of the proposed methods was achieved according to ICH guidelines and satisfactory results were obtained indicating that the developed methods can be used for quality control analysis of AML and CEL concerning its impurity. No significant difference was observed when the obtained results of the developed methods were statistically compared with the reported HPLC method.

PMID:34273891 | DOI:10.1016/j.saa.2021.120137

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Nevin Manimala Statistics

Secukinumab effects on disease burden, patient needs and benefits, and treatment satisfaction in patients with plaque psoriasis across European regions: Patient perspective data from the PROSE study

J Eur Acad Dermatol Venereol. 2021 Jul 17. doi: 10.1111/jdv.17525. Online ahead of print.

ABSTRACT

BACKGROUND: Cross-cultural differences in healthcare policies and patient-physician communication may influence the quality of care and patients’ perceived benefits and satisfaction with psoriasis treatment.

OBJECTIVES: To compare the disease burden and patient needs at baseline, and patient benefits and satisfaction with secukinumab treatment across Europe.

METHODS: PROSE was an open-label, prospective, non-randomised, stratified multicentre study of 52 weeks of secukinumab treatment, in 16 European countries. Secondary analysis of the PROSE study data by European regions was performed to identify cross-cultural differences in disease burden and patient needs at baseline, and in clinical improvement, patient-reported treatment benefits and satisfaction at 52 weeks post-treatment.

RESULTS: At baseline, Dermatology Life Quality Index impairment was reported to be greater in patients from Eastern Europe (EE:15.4±7.1) versus Northern Europe (NE:13.3±6.7) and Western Europe (WE:13.6±6.9), but while differences were statistically significant (F-test=5.5, p<0.001), their clinical significance is uncertain. There were no significant differences between regions in Psoriasis Area and Severity Index at baseline (F-test=1.6). There were considerable differences in patients’ needs (Patient Need Questionnaire) between geographical regions, with WE focused more on reducing physical impairment versus Southern Europe [SE]/EE), EE on reducing social impairment (versus NE/WE), and SE on reducing impairment due to therapy (versus NE/WE). At Week 52, patients from EE reported more benefits (Patient Benefit Index) with secukinumab treatment (versus WE/SE), while patients from NE reported higher global treatment satisfaction (versus SE).

CONCLUSIONS: Differences in patients’ needs and treatment satisfaction across Europe are likely a result of diverse medical systems, socio-economic status and infrastructural access. A patient-centred approach to treating psoriasis may fulfil patient needs and maximise treatment satisfaction. (NCT02752776).

PMID:34273904 | DOI:10.1111/jdv.17525

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Nevin Manimala Statistics

Development of an ergonomic design process for smartphone hard key locations

Appl Ergon. 2021 Jul 14;97:103532. doi: 10.1016/j.apergo.2021.103532. Online ahead of print.

ABSTRACT

Smartphone hard key locations need to be ergonomically determined to improve grip stability and operational efficiency for users’ convenience. The present study proposed an ergonomic design process that determines smartphone hard key locations by statistically analyzing the preferred hard key control areas of users with various hand sizes based on users’ preferred grip postures and hard key control areas. The proposed design process analyzes the characteristics of product design, user, task, and use context, the types of preferred grip posture, the preference distribution of grip posture, and the preference distribution of hard-key area, and then recommends the locations of hard keys by considering the preference distribution of hard-key area and design constraints. The proposed design process was applied to a smartphone with a 5-inch screen, resulting in 77-96 mm from the bottom of the device for a volume key to 20 mm on the left side and 88-97 mm for a power key to 10 mm on the right side. The proposed design process for the determination of smartphone hard-key locations would be of use to determine the locations of various portable product interfaces.

PMID:34273813 | DOI:10.1016/j.apergo.2021.103532

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Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: An analysis of the phase III ARAMIS trial

Eur J Cancer. 2021 Jul 14;154:138-146. doi: 10.1016/j.ejca.2021.06.010. Online ahead of print.

ABSTRACT

BACKGROUND: In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Herein, we present analyses of patient-reported health-related quality of life (HRQoL) outcomes.

PATIENTS AND METHODS: This double-blind, placebo-controlled, phase III trial randomised patients with nmCRPC and prostate-specific antigen doubling time ≤10 months to darolutamide 600 mg (n = 955) twice daily or matched placebo (n = 554) while continuing ADT. The primary end-point was MFS; the secondary end-points included OS and time to pain progression. In this analysis, HRQoL was assessed by the time to deterioration using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25) subscales.

RESULTS: Darolutamide significantly prolonged time to deterioration of FACT-P PCS versus placebo (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.70-0.91; P = 0.0005) at the primary analysis (cut-off date: 3rd September 2018). Time to deterioration of EORTC QLQ-PR25 outcomes showed statistically significant delays with darolutamide versus placebo for urinary (HR 0.64, 95% CI 0.54-0.76; P < 0.0001) and bowel (HR 0.78, 95% CI 0.66-0.92; P = 0.0027) symptoms. Time to worsening of hormonal treatment-related symptoms was similar between the two groups.

CONCLUSION: In patients with nmCRPC who are generally asymptomatic, darolutamide maintained HRQoL by significantly delaying time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo.

PMID:34273811 | DOI:10.1016/j.ejca.2021.06.010

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Effects of porcine bone marrow-derived platelet-rich plasma on bone marrow-derived mesenchymal stem cells and endothelial progenitor cells

Tissue Cell. 2021 Jun 29;71:101587. doi: 10.1016/j.tice.2021.101587. Online ahead of print.

ABSTRACT

This study investigated the abundance of pro-regenerative growth factors in bone marrow-derived platelet-rich plasma (BM-PRP) and their effects on bone marrow-derived mesenchymal stem cells (BM-MSC) and bone marrow-derived endothelial progenitor cells (BM-EPC). Four 4-5 months-old domestic pigs were included, and each underwent bone marrow aspiration from its humerus bones and processed into bone marrow aspiration concentrate (BMAC) samples. The plasma and cellular portions of BMAC were subsequently separated and collected. The concentration of growth factors including BMP-2, PDGF-BB, TGF-β1 and VEGF in the plasma portion was measured and compared between BM-PRP and bone marrow-derived platelet-poor plasma (BM-PPP). It was found that platelet count was significantly higher in BM-PRP than in BM-PPP, but the concentration of above-mentioned growth factors was not significantly different between BM-PRP and BM-PPP. As most existing literature has indicated the regenerative potency of PRP, this study focused on assessing the effect of BM-PRP treatment on BM-MSC and BM-EPC proliferation, osteogenic differentiation and angiogenesis capacity by comparing samples with 2.5% BM-PRP treatment and samples without BM-PRP treatment (control). In response to BM-PRP treatment, the cellular doubling time increased with culturing time and was significantly shorter in the BM-PRP-treated samples than in control samples. For osteogenic differentiation, BM-PRP-treated BM-MSCs demonstrated a time-dependent increase in alkaline phosphatase (ALP) activity and expression levels of osteogenic differentiation markers. For the expression of angiogenic genes, none of the differences reached statistical significance despite a tendency of stronger expression at day 18 in BM-PRP-treated BM-EPCs. In conclusion, this in vitro study suggests that most BMP-2, PDGF-BB, TGF-β1 and VEGF-A contained in BM-PRP are not platelet-released and BM-PRP may have some stimulation (less than 1-fold) for MSC, EPC proliferation and MSC osteogenic differentiation.

PMID:34273802 | DOI:10.1016/j.tice.2021.101587

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Nevin Manimala Statistics

The effect of systemic and local risk factors on triggering peripherally inserted central catheter-related thrombosis in cancer patients: A prospective cohort study based on ultrasound examination and structural equation modeling

Int J Nurs Stud. 2021 Jun 18;121:104003. doi: 10.1016/j.ijnurstu.2021.104003. Online ahead of print.

ABSTRACT

BACKGROUND: The negative synergistic effect of cancer and a peripherally inserted central catheter could significantly increase the incidence of thrombosis. Rather than identifying risk factors for peripherally inserted central catheter-related thrombosis, exploring the effect of these risk factors might be a promising method to improve the outcomes of thrombosis.

OBJECTIVES: To analyze the effect of systemic and local risk factors on triggering peripherally inserted central catheter-related thrombosis in the first two weeks post-insertion in cancer patients.

DESIGN: A prospective cohort study.

SETTING: The study was conducted at a 4500-bed university-affiliated medical center in China.

PARTICIPANTS: One hundred seventy-three cancer patients with peripherally inserted central catheters were included.

METHODS: Peripherally inserted central catheter-related thrombosis was assessed using ultrasound at a series of timepoints, once every two days post-insertion. Data on age, body mass index, blood hypercoagulation, insertion attempts, catheter-to-vein ratio, and blood flow velocity were collected as risk factors. Descriptive statistics and structural equation modeling were used to describe the study samples and analyze the effects of systemic and local risk factors.

RESULTS: Among the 173 cancer patients included, 126 (72.8%) patients were diagnosed with peripherally inserted central catheter-related thrombosis. Most thromboses (n = 118, 93.7%) were detected within five days, and 100% were detected within nine days post-insertion. Structural equation modeling analysis showed that local risk factors [catheter-to-vein ratio (standardized path coefficient = 0.32, p < 0.05) and blood flow velocity (standardized path coefficient = -0.35, p < 0.05)] had a greater effect than systemic factors [age (standardized path coefficient = 0.13, p < 0.05) and blood hypercoagulation (standardized path coefficient = 0.17, p < 0.05)] on triggering peripherally inserted central catheter-related thrombosis.

CONCLUSION: Peripherally inserted central catheter-related thrombosis is quite common and can occur very early post-insertion in cancer patients. Among the common risk factors, local risk factors reflecting peripherally inserted central catheter technology itself had a greater effect than systemic risk factors reflecting predisposition to thrombosis. Clinical Registration: Clinical Trials ChiCTR1900024890.

PMID:34273807 | DOI:10.1016/j.ijnurstu.2021.104003

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Nevin Manimala Statistics

The Impact of Hemoglobin A1c on Post-operative Outcomes in Bariatric Surgery Patients

J Surg Res. 2021 Jul 14;267:636-641. doi: 10.1016/j.jss.2021.06.022. Online ahead of print.

ABSTRACT

INTRODUCTION: Pre-operative hemoglobin (Hb) A1c levels ≥ 8% can lead to increased post-operative complications. In bariatric surgery patients, attaining a pre-operative HbA1c < 8% can be a challenge. The purpose of this study was to identify the association of pre-operative HbA1c on post-operative outcomes in bariatric surgery patients.

MATERIAL AND METHODS: A retrospective chart review was conducted on diabetic patients (HbA1c ≥ 6.5%) who underwent primary bariatric surgery at a single institution between the years 2013 and 2019. Patients were divided into two groups based on their pre-operative HbA1c levels of < 8% and ≥ 8%. Univariate analyses were performed to determine an association between pre-operative HbA1c levels and post-operative outcomes.

RESULTS: There were 351 primary diabetic bariatric surgery patients, 270 HbA1c <8%, and 81 HbA1c ≥ 8%. Procedure selection was significantly different between the HbA1c < 8% and HbA1c ≥ 8% group (49.3% sleeve, 50.4% bypass and 0.4% band versus 43.2% sleeve, 53.1% bypass and 3.7% band respectively, P < 0.04). There was no statistically significant difference in any 30-day post-operative outcome between the two groups. Post-operative HbA1c was significantly less in the HbA1c < 8% group at 3-6 month (6.0% ± 0.9 versus 7.4% ± 1.4, P <0.001) and 6-12 month (6.0% ± 1.1 versus 7.2% ± 1.4, P <0.001) follow-up.

CONCLUSIONS: This study demonstrated no difference in post-operative outcomes of primary bariatric surgery patients based on a HbA1c cut-off of 8%. This highlights that bariatric surgery can be considered and safely performed in patients with a pre-operative HbA1c ≥ 8%.

PMID:34273793 | DOI:10.1016/j.jss.2021.06.022

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Nevin Manimala Statistics

Laughter as a paradigm of socio-emotional signal processing in dementia

Cortex. 2021 Jun 23;142:186-203. doi: 10.1016/j.cortex.2021.05.020. Online ahead of print.

ABSTRACT

Laughter is a fundamental communicative signal in our relations with other people and is used to convey a diverse repertoire of social and emotional information. It is therefore potentially a useful probe of impaired socio-emotional signal processing in neurodegenerative diseases. Here we investigated the cognitive and affective processing of laughter in forty-seven patients representing all major syndromes of frontotemporal dementia, a disease spectrum characterised by severe socio-emotional dysfunction (twenty-two with behavioural variant frontotemporal dementia, twelve with semantic variant primary progressive aphasia, thirteen with nonfluent-agrammatic variant primary progressive aphasia), in relation to fifteen patients with typical amnestic Alzheimer’s disease and twenty healthy age-matched individuals. We assessed cognitive labelling (identification) and valence rating (affective evaluation) of samples of spontaneous (mirthful and hostile) and volitional (posed) laughter versus two auditory control conditions (a synthetic laughter-like stimulus and spoken numbers). Neuroanatomical associations of laughter processing were assessed using voxel-based morphometry of patients’ brain MR images. While all dementia syndromes were associated with impaired identification of laughter subtypes relative to healthy controls, this was significantly more severe overall in frontotemporal dementia than in Alzheimer’s disease and particularly in the behavioural and semantic variants, which also showed abnormal affective evaluation of laughter. Over the patient cohort, laughter identification accuracy was correlated with measures of daily-life socio-emotional functioning. Certain striking syndromic signatures emerged, including enhanced liking for hostile laughter in behavioural variant frontotemporal dementia, impaired processing of synthetic laughter in the nonfluent-agrammatic variant (consistent with a generic complex auditory perceptual deficit) and enhanced liking for numbers (‘numerophilia’) in the semantic variant. Across the patient cohort, overall laughter identification accuracy correlated with regional grey matter in a core network encompassing inferior frontal and cingulo-insular cortices; and more specific correlates of laughter identification accuracy were delineated in cortical regions mediating affective disambiguation (identification of hostile and posed laughter in orbitofrontal cortex) and authenticity (social intent) decoding (identification of mirthful and posed laughter in anteromedial prefrontal cortex) (all p < .05 after correction for multiple voxel-wise comparisons over the whole brain). These findings reveal a rich diversity of cognitive and affective laughter phenotypes in canonical dementia syndromes and suggest that laughter is an informative probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative disease.

PMID:34273798 | DOI:10.1016/j.cortex.2021.05.020

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Prenatal diagnosis of isolated clubfoot: Diagnostic accuracy and long-term postnatal outcomes

Eur J Obstet Gynecol Reprod Biol. 2021 Jul 7;264:60-64. doi: 10.1016/j.ejogrb.2021.07.009. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate concordance between prenatal and postnatal diagnosis of congenital talipes equinovarus (cTEV), rates of surgery and postnatal outcomes in relation to the prenatal classification of severity.

STUDY DESIGN: This is a retrospective observational cohort study on fetuses with a prenatal diagnosis of cTEV between 2004 and 2018. All cases of isolated cTEV in singleton pregnancies were included. Postnatally, the Ponseti method was applied. Children were followed-up postnatally for at least two years, with a specific focus on neurodevelopmental outcome.

RESULTS: The cohort included 81 fetuses with a prenatal diagnosis of cTEV confirmed postnatally in 86.4% of cases. Concordance between prenatal and postnatal assessment was good for both laterality and degree of severity (k = 0.61 and 0.66, respectively). The average Pirani score, number of casts and rates of Achilles tendon tenotomy were higher for III degree cTEV (p < 0.001). Within this group only, the rate of relapse was 11% and the rates of major surgery was 6%. The postnatal outcome was normal in 68.6% newborns, while 14% of cases had a diagnosis of minor additional findings and 17% had an impairment of neurological development. None of the outcome was statistically correlated to the prenatal assessment of laterality or degree.

CONCLUSIONS: The accuracy of prenatal ultrasound for isolated cTEV is 86% with a false positive diagnosis of 14%. The grade of cTEV assigned prenatally correlates to postnatal severity and longer orthopedic rehabilitation in terms of number of casts and need of surgery. The assessment of the correlation between cTEV and neurological impairment requires further prospective studies on larger cohorts.

PMID:34273754 | DOI:10.1016/j.ejogrb.2021.07.009