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Nevin Manimala Statistics

Heartbeat optical coherence elastography: corneal biomechanics in vivo

J Biomed Opt. 2021 Feb;26(2). doi: 10.1117/1.JBO.26.2.020502.

ABSTRACT

SIGNIFICANCE: Mechanical assessment of the cornea can provide important structural and functional information regarding its health. Current clinically available tools are limited in their efficacy at measuring corneal mechanical properties. Elastography allows for the direct estimation of mechanical properties of tissues in vivo but is generally performed using external excitation force.

AIM: To show that heartbeat optical coherence elastography (Hb-OCE) can be used to assess the mechanical properties of the cornea in vivo.

APPROACH: Hb-OCE was utilized to detect Hb-induced deformations in the rabbit cornea in vivo without the need for external excitation. Furthermore, we demonstrate how this technique can distinguish corneal stiffness between untreated (UT) and crosslinked (CXL) tissue.

RESULTS: Our results demonstrate that stiffness changes in the cornea can be detected using only the Hb-induced deformations in the cornea. Additionally, we demonstrate a statistically significant difference in strain between the UT and CXL corneas.

CONCLUSIONS: Hb-OCE may be an effective tool for assessing the mechanical properties of the cornea in vivo without the need for external excitation. This tool may be effective for clinical assessment of corneal mechanical properties because it only requires optical coherence tomography imaging and data processing.

PMID:33624461 | DOI:10.1117/1.JBO.26.2.020502

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The relationship between language difficulties, psychosocial difficulties and speech-language pathology service access in the community

Int J Lang Commun Disord. 2021 Feb 23. doi: 10.1111/1460-6984.12593. Online ahead of print.

ABSTRACT

BACKGROUND: A range of factors may impact whether children access speech-language pathology (SLP) services, beyond their communication difficulties. For instance, co-occurring psychosocial difficulties may amplify children’s observable difficulties, leading to greater access. It is important to examine such associations because they may reflect inherent differences between children with language difficulties who access services and those who do not, indicating under-servicing for subgroups in the community.

AIMS: The first aim was to examine possible differences in psychosocial difficulties between children with language difficulties who did versus did not access SLP services in the past 12 months. The second aim was to examine the unique contribution of psychosocial difficulties to service access, over and above language difficulties and other common predictors of service access.

METHODS & PROCEDURES: Analyses were carried out on data gathered from 808 eleven-year-old children who took part in the Early Language in Victoria Study (ELVS). Children were categorized as having language difficulties based on their CELF-4 Core Language Score with a cut-point of > 1.25 SD below the mean. The primary outcome measure was access to SLP services in the past 12 months. Comparison and predictor variables included children’s psychosocial difficulties, language skills, relevant demographic variables (gender, caregiver education) and prior SLP access.

OUTCOMES & RESULTS: A total of 42 children with language difficulties who had accessed SLP services had significantly greater psychosocial difficulties than those who had not (SDQ Total Difficulties, U = 53.00, z = -4.080, p < 0.001). Using binary logistic regression, a model examining child gender, caregiver education, psychosocial difficulties (internalizing and externalizing behaviours), language difficulties and prior SLP access (in earlier years) was significant χ2 (8) = 137.285, p< 0.001, with increased externalizing difficulties (OR = 1.213, p < 0.001), increased communication difficulties (OR = 0.949, p < 0.001), and prior SLP access (OR = 7.430, p < 0.001) identified as unique predictors of service access.

CONCLUSIONS & IMPLICATIONS: The results indicate that children with language difficulties who have comorbid psychosocial difficulties are more likely to access services than those who do not. Accordingly, children with language difficulties who access clinical services may require interdisciplinary support, while children without co-morbid psychosocial difficulties may be under-referred for SLP services. What this paper adds What is already known on this subject There is evidence that a range of personal and contextual factors impact the likelihood of a person accessing healthcare services beyond the specific issue of concern. What this paper adds to existing knowledge In this population-based study, we provide statistical evidence that children with language difficulties who had higher levels of psychosocial difficulties were more likely to access SLP services than those who had lower levels. What are the potential or actual clinical implications of this work? Children with language difficulties who access SLP services may require support for psychosocial difficulties, while children who do not have comorbid difficulties may be underserviced in the community.

PMID:33624420 | DOI:10.1111/1460-6984.12593

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Validation of oral brushing as a non-invasive technique for the identification of feline oral squamous cell carcinoma by DNA methylation and TP53 mutation analysis

Vet Comp Oncol. 2021 Feb 23. doi: 10.1111/vco.12688. Online ahead of print.

ABSTRACT

Feline oral squamous cell carcinoma (FOSCC) is a frequent and progressively invasive tumour. Early lesions are difficult to recognize based on the sole clinical examination and may be misinterpreted as non-neoplastic. Mutations of TP53 and epigenetic alterations of specific genes are present in FOSCC and may be early detected. Aim of this prospective study was to investigate the DNA methylation pattern of a 17-gene panel and TP53 mutational status of FOSCC cytological samples obtained by oral brushing. Results were compared with a control group, in order to validate this non-invasive procedure for the screening of FOSCC. In FOSCC, the same analyses were carried out on the corresponding histological sample, if available. Thirty-five FOSCC and 60 controls were included. Mutations of TP53 were detected in 17 FOSCC brushings (48%) and in none of the controls (P < 0.001). Six genes (ZAP70, FLI1, MiR124-1, KIF1A, MAGEC2, MiR363) were differentially methylated in FOSCC and were included in a methylation score. An algorithm based on TP53 mutational status and methylation score allowed to differentiate FOSCC from controls with a 69% sensitivity and a 97% specificity (accuracy, 86%). In 19 FOSCC histological samples, TP53 mutational status was fully concordant with brushings, and a positive methylation score was observed in all cases. These results are promising for the identification of FOSCC by oral brushing, although some factors may limit the accuracy of this technique, and further studies are required to assess its reproducibility in clinical practice. This article is protected by copyright. All rights reserved.

PMID:33624422 | DOI:10.1111/vco.12688

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Adolescent electronic cigarette counselling: knowledge, attitudes and perceived barriers among clinical staff in a primary care setting

J Eval Clin Pract. 2021 Feb 23. doi: 10.1111/jep.13553. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess knowledge, attitudes, and perceived barriers (KAP) regarding e-cigarette use counselling among adolescent healthcare clinical staff in an urban system, and to compare results between providers and rooming staff.

METHODS: Primary care clinical staff (n = 169) completed an anonymous survey. Descriptive statistics and Chi-square tests were used to summarize data and compare KAP between medical providers and rooming staff.

RESULTS: Staff wanted to learn more about e-cigarettes (87.6%). The most common knowledge deficits were how to use the 5As + 5Rs model for tobacco cessation counselling (66.7%) and the chemical content of e-liquids (55.4%), with no differences across groups. Overall, 58% of providers expressed confidence in their ability to talk with adolescent patients about e-cigarette use. The most common barriers to counselling were low knowledge about e-cigarettes (74.0%) and how to refer adolescent patients for cessation support (43.8%).

CONCLUSIONS: Provider and rooming staff expressed similar educational needs surrounding e-cigarettes, counselling, and treatment for adolescent patients. Clinical staff expressed confidence in their ability to affect change. There were no differences in the identified knowledge gaps or barriers to care between rooming staff and providers, suggesting that the same educational format can be used to target both groups.

PMID:33624429 | DOI:10.1111/jep.13553

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Impact of different training modalities on anthropometric outcomes in patients with obesity: A systematic review and network meta-analysis

Obes Rev. 2021 Feb 23:e13218. doi: 10.1111/obr.13218. Online ahead of print.

ABSTRACT

Obesity management guidelines consistently advise aerobic training for weight loss, whereas recommendations for other training modalities are sparse. This systematic review and network meta-analysis (NMA) aimed to compare the long-term effects of different training modalities on anthropometric outcomes in patients with obesity. MEDLINE, Cochrane CENTRAL, and Web of Science were searched to identify the following: (1) randomized controlled trials (RCTs); (2) conducted in adults with a mean body mass index (BMI) ≥30 kg/m2 ; (3) comparing aerobic, resistance, combined, or high-intensity interval training head-to-head or to control for ≥6 months; and (4) reporting changes in body weight (BW), BMI, waist circumference (WC), fat mass (FM), or fat-free mass (FFM). Random-effects NMA models were fitted in a frequentist approach. GRADE framework was used to assess certainty of evidence. Thirty-two RCTs with 4774 participants with obesity were included in this review. Aerobic training was ranked as best for improving BW, BMI, and WC and combined training for improving FM, as well as equally with resistance training most effective for improving FFM. Low to moderate certainty of evidence supports use of aerobic training to improve anthropometric outcomes in obesity, and its combination with resistance training provides additional benefit for reducing FM and increasing FFM.

PMID:33624411 | DOI:10.1111/obr.13218

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Longitudinal study of physical activity with various methods in maintenance hemodialysis patients

Hemodial Int. 2021 Feb 23. doi: 10.1111/hdi.12914. Online ahead of print.

ABSTRACT

INTRODUCTION: The purpose was to make longitudinal measurements of physical activity and study whether physical activity decreases over time in maintenance hemodialysis (MHD) patients.

METHODS: This was an observational study, where MHD patients were considered in a 12-month follow-up. Laboratory variables and physical activity were tested three times over 12-months in 124 hemodialysis patients. Physical activity was measured using the Human Activity Profile (HAP), the Stanford 7-day Physical Activity Recall Questionnaire (PAR), and walking speed. Repeated measure variance analysis was used to analyze changes of physical activity. The Bonferroni method was used to do pairwise comparisons.

FINDINGS: The proportion of decreased physical activity increased (P < 0.05). The maximal activity score (MAS), adjusted activity score (AAS), HAP dimension scores, and walking speed all decreased at the three time points studied (P < 0.001). At the same time, moderate physical activities and PAR values changed at three time points (P < 0.05). Pairwise comparisons showed that between the baseline and the 6-month follow-up, MAS, AAS, the scores of personal/household work, entertainment/social, independent exercise, leg effort, and back effort, all decreased(P < 0.05). Between the baseline and the 12-month follow-up, and between the 6-month follow-up and the 12-month follow-up, all the scores of HAP and walking speed decreased significantly (P < 0.001). Between the baseline and the 6-month follow-up, moderate physical activities and PAR values increased (P < 0.05). However, between the baseline and the 12-month follow-up, and between the 6-month follow-up and the 12-month follow-up, moderate physical activities and PAR did not change statistically.

CONCLUSION: Physical activity decreased in hemodialysis patients in the 12-month follow-up.

PMID:33624415 | DOI:10.1111/hdi.12914

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Neurological manifestations in patients hospitalized with COVID-19: a retrospective analysis from a large cohort in Northern Italy

Eur J Neurosci. 2021 Feb 23. doi: 10.1111/ejn.15159. Online ahead of print.

ABSTRACT

SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19. All individuals admitted for to our hospital COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in 1) isolated respiratory, 2) combined respiratory and neurologic, 3) isolated neurologic and 4) stroke manifestations. Descriptive statistics and non-parametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to post-infective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p=0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI 0.206-0.769, p=0.006). Neurologic manifestations in COVID-19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms.

PMID:33624380 | DOI:10.1111/ejn.15159

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Principal stratum strategy: Potential role in drug development

Pharm Stat. 2021 Feb 23. doi: 10.1002/pst.2104. Online ahead of print.

ABSTRACT

A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding the treatment effect in subpopulations of patients, which would experience clinical or disease related events post-randomization. Events that occur after treatment initiation and potentially affect the interpretation or the existence of the measurements are called intercurrent events in the ICH E9(R1) guideline. If the intercurrent event is a consequence of treatment, randomization alone is no longer sufficient to meaningfully estimate the treatment effect. Analyses comparing the subgroups of patients without the intercurrent events for intervention and control will not estimate a causal effect. This is well known, but post-hoc analyses of this kind are commonly performed in drug development. An alternative approach is the principal stratum strategy, which classifies subjects according to their potential occurrence of an intercurrent event on both study arms. We illustrate with examples that questions formulated through principal strata occur naturally in drug development and argue that approaching these questions with the ICH E9(R1) estimand framework has the potential to lead to more transparent assumptions as well as more adequate analyses and conclusions. In addition, we provide an overview of assumptions required for estimation of effects in principal strata. Most of these assumptions are unverifiable and should hence be based on solid scientific understanding. Sensitivity analyses are needed to assess robustness of conclusions.

PMID:33624407 | DOI:10.1002/pst.2104

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Outcomes after intensive care unit admission in newly diagnosed diffuse large B-cell lymphoma patients: a real-life study

Eur J Haematol. 2021 Feb 23. doi: 10.1111/ejh.13606. Online ahead of print.

ABSTRACT

We conducted a retrospective study to analyze the prognostic factors impacting the overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients undergoing first-line therapy and admitted to intensive care unit (ICU) compared to a control cohort who did not required ICU admission. Between January 1, 2008, and December 31, 2018, 828 patients were diagnosed with DLBCL at our institution, including 72 patients who were required ICU admission during disease course. Among them, forty-five patients undergoing homogeneous first-line therapy with /R-CHOP-like regimen and ICU-admitted were selected for the present analysis. Control “non-ICU” DLBCL patients were matched by age, IPI score and treatment received. The median age at ICU admission was 65 years, 97.8% of patients displayed advanced-stage disease (III/IV), and 84.4% had a high IPI score (3 – 5). The main reasons for ICU admission were acute respiratory failure (40.0%) and septic shock (33.3%). The ICU mortality rate was 33.3%. The 2-year PFS was lower in ICU survivors patients than in non-ICU patients: 31.7% (95% CI 18.5 – 54.1) vs 60.8% (95% CI 51.2 – 72.1, p=0.00049). Admission to the ICU is an event that clearly impacts the outcomes of patients with DLBCL, until two years after the event. ICU prognosis seems mainly related to critical patient severity at admission rather than lymphoma-related prognostic factors (IPIs), suggesting that ICU admission criteria should not be based only on the lymphoma prognosis.

PMID:33624346 | DOI:10.1111/ejh.13606

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Improving the sensitivity of spin-echo fMRI at 3T by highly accelerated acquisitions

Magn Reson Med. 2021 Feb 23. doi: 10.1002/mrm.28715. Online ahead of print.

ABSTRACT

PURPOSE: Spin-echo (SE) functional MRI (fMRI) can be highly advantageous compared to gradient-echo (GE) fMRI with respect to magnetic field-inhomogeneity artifacts. However, at 3T, the majority of blood oxygenation level-dependent (BOLD) fMRI experiments are performed using T2∗ -weighted GE sequences because of their superior sensitivity compared to SE-fMRI. The presented SE implementation of a highly accelerated GE pulse sequence therefore aims to improve the sensitivity of SE-fMRI while profiting from a reduction of susceptibility-induced signal dropout.

METHODS: Spin-echo MR encephalography (SE-MREG) is compared with the more conventionally used spin-echo echo-planar imaging (SE-EPI) and spin-echo simultaneous multislice (SE-SMS) at 3T in terms of capability to detect neuronal activations and resting-state functional connectivity. For activation analysis, healthy subjects underwent consecutive SE-MREG (pulse repetition time [TR] = 0.25 seconds), SE-SMS (TR = 1.3 seconds), and SE-EPI (TR = 4.4 seconds) scans in pseudorandomized order applied to a visual block design paradigm for generation of t-statistics maps. For the investigation of functional connectivity, additional resting-state data were acquired for 5 minutes and a seed-based correlation analysis using Stanford’s FIND (Functional Imaging in Neuropsychiatric Disorders) atlas was performed.

RESULTS: The increased sampling rate of SE-MREG relative to SE-SMS and SE-EPI improves the sensitivity to detect BOLD activation by 33% and 54%, respectively, and increases the capability to extract resting-state networks. Compared with a brain region that is not affected by magnetic field inhomogeneities, SE-MREG shows 2.5 times higher relative signal strength than GE-MREG in mesial temporal structures.

CONCLUSION: SE-MREG offers a viable possibility for whole-brain fMRI with consideration of brain regions that are affected by strong susceptibility-induced magnetic field gradients.

PMID:33624352 | DOI:10.1002/mrm.28715