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Basic gait pattern and impact of fall risk factors on gait among older adults in India

Gait Posture. 2021 Apr 30;88:16-21. doi: 10.1016/j.gaitpost.2021.04.043. Online ahead of print.

ABSTRACT

BACKGROUND: An unstable gait pattern is an indicator of an increased risk of falls among older adults. Data on basic gait parameters is useful in the early identification of gait impairment. However, reference gait measurements are not available in low- and middle-income countries.

RESEARCH QUESTION: What are the normative reference values of gait parameters and do fall risk factors such as impaired balance, functional difficulty, and multimorbidity affect the gait patterns of older adults in India?

METHODS: A cross-sectional data of 659 older adults were collected using a semi-structured schedule. Gait parameters were measured using wearable sensors. Descriptive statistics, independent t-test, and one-way ANCOVA were used to determine the significant difference (p < 0.05) in gait parameters across the risk factors.

RESULTS: A mean stride length of 123.00 ± 15.19 cm, stride velocity of 110.57 ± 17.57 cm/s, and a cadence of 106.14 ± 11.44 steps/minute were reported in the study. Functional difficulties and balance impairment were the two major risk factors that affected stride velocity, stride length, and cadence after adjusting for age and height. No difference in gait parameters was observed among participants with and without multimorbidity.

SIGNIFICANCE: This study provides a baseline or reference values of various gait parameters measured on a large sample of population aged 60 and above from India. Assessment of gait patterns and associated risk factors in a clinical setup will help identify the older adults at risk of falls and reduce the enormous burden of fall injuries. Since gait parameters show a large variation across geographical regions, it is important to have region-specific reference values.

PMID:33951574 | DOI:10.1016/j.gaitpost.2021.04.043

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Exploring the effectiveness of the TSR-based protein 3-D structural comparison method for protein clustering, and structural motif identification and discovery of protein kinases, hydrolases, and SARS-CoV-2’s protein via the application of amino acid grouping

Comput Biol Chem. 2021 Mar 29;92:107479. doi: 10.1016/j.compbiolchem.2021.107479. Online ahead of print.

ABSTRACT

Development of protein 3-D structural comparison methods is essential for understanding protein functions. Some amino acids share structural similarities while others vary considerably. These structures determine the chemical and physical properties of amino acids. Grouping amino acids with similar structures potentially improves the ability to identify structurally conserved regions and increases the global structural similarity between proteins. We systematically studied the effects of amino acid grouping on the numbers of Specific/specific, Common/common, and statistically different keys to achieve a better understanding of protein structure relations. Common keys represent substructures found in all types of proteins and Specific keys represent substructures exclusively belonging to a certain type of proteins in a data set. Our results show that applying amino acid grouping to the Triangular Spatial Relationship (TSR)-based method, while computing structural similarity among proteins, improves the accuracy of protein clustering in certain cases. In addition, applying amino acid grouping facilitates the process of identification or discovery of conserved structural motifs. The results from the principal component analysis (PCA) demonstrate that applying amino acid grouping captures slightly more structural variation than when amino acid grouping is not used, indicating that amino acid grouping reduces structure diversity as predicted. The TSR-based method uniquely identifies and discovers binding sites for drugs or interacting proteins. The binding sites of nsp16 of SARS-CoV-2, SARS-CoV and MERS-CoV that we have defined will aid future antiviral drug design for improving therapeutic outcome. This approach for incorporating the amino acid grouping feature into our structural comparison method is promising and provides a deeper insight into understanding of structural relations of proteins.

PMID:33951604 | DOI:10.1016/j.compbiolchem.2021.107479

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“NDR: Prototype of National Dose Register for Latin America. Main experiences in their design and implementation”

J Radiol Prot. 2021 May 5. doi: 10.1088/1361-6498/abfe50. Online ahead of print.

ABSTRACT

Several national regulations and good international practices promote the existence of a central register with the results of individual radiological monitoring. In the majority of the countries (Latin American region), dosimetry data were neither harmonized, nor managed by a unique database, therefore the possibility of using such data, for proper characterization of the radiological conditions, integrally at national level, in a territory or a sector, and by practices or occupational categories, was very limited. All these considerations justified the need for developing a prototype of National Dose Register (NDR) for Latin America. The main objectives were the strengthening of safety supervision in nuclear applications and the surveillance system for occupational exposure as well as the centralization of personal dosimetry data, compiling all doses evaluated by the different dosimetric service providers. The experience of Cuba and Brazil in the implementation of their national registers was well known and accordingly used as bases to design this software. The first version of the NDR prototype, developed in the Spanish language has been designed, developed, and validated. So far, sixteen countries have started to implement the NDR. The present work describes aspects such as the technical bases of the NDR design, its characteristics, and functionalities. Experience gained during implementation in Latin America is also addressed. Having a common system of dosimetric information management in the region has opened an important space for scientific exchanges between the countries and their competent authorities. The NDR implementation has provided regulatory authorities with a tool that permits the verification of the level of compliance with dose limits and restrictions, as well as to carry out statistics assessments of the results of individual radiological surveillance that may permit evaluation of the appropriateness and effectiveness of radiation protection programs implemented in the practices and to contribute to their optimization.

PMID:33951614 | DOI:10.1088/1361-6498/abfe50

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PROGNOSTIC VALUE OF CHARLSON COMORBIDITY INDEX IN ACUTE EMBOLIC LOWER LIMB ISCHAEMIA PATIENTS

Ann Vasc Surg. 2021 May 2:S0890-5096(21)00373-3. doi: 10.1016/j.avsg.2021.04.022. Online ahead of print.

ABSTRACT

INTRODUCTION: Charlson Comorbidity Index (CCI) is commonly used in outcome studies to adjust for patient comorbid conditions but has not been specifically validated for use in acute embolic lower limb ischaemia (AELLI).

OBJECTIVES: The aim of this study was to access whether a high CCI score unadjusted (CCIu) and adjusted (CCIa) by age relates to major amputation and mortality after a first episode of AELLI.

METHODS: The last 100 patients presenting with the first event of AELLI submitted to embolectomy at our Vascular Surgery Department were retrospectively evaluated. Patient characteristics, pre- and post-operative period variables were collected and CCIu and CCIa calculated. Survival predictors were analyzed using Cox regression. The area under the curve of the receiver operating characteristic curves was calculated to validate and determine the discriminating ability of CCIu and CCIa in predicting amputation rate and 30-day mortality. Youden index was used to determine the critical value. Survival analysis was performed with Kaplan-Meier method and differences between survival curves were tested with Log-Rank test. A p value of <.05 was considered statistically significant.

RESULTS: The mean age was 80.03±10.776 years and the mean follow-up 19.28±7.929 months. Amputation rate was 16%, 30-day mortality 21% and long-term mortality 42%. Patients with CCIu≥3 compared with patients with CCIu<3 had higher amputation rate (37.5% vs. 1.7%; OR:35.400), 30-day mortality (47.5% vs. 3.3%; OR:35.400) and global mortality (p=.00). Also, patients with CCIa≥6 compared with patients with CCIa<6 had higher amputation rate (34.1% vs. 1.8%; OR:28.488), 30-day mortality (47.7% vs. 0.0%) and global mortality (p=.00). Multivariate analysis showed that both CCIu and CCIa were independent predictors of amputation rate and 30-day mortality.

CONCLUSION: CCIu and CCIa have proven to be good predictors of amputation rate and survival, thus being a valuable prognostic factor in patients presenting with the first event of AELLI.

PMID:33951526 | DOI:10.1016/j.avsg.2021.04.022

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Outcome of femoral-popliteal bypass procedures in different ethnic groups in England: A retrospective analysis of Hospital Episode Statistics

Ann Vasc Surg. 2021 May 2:S0890-5096(21)00369-1. doi: 10.1016/j.avsg.2021.04.018. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies, mainly from the United States, have reported worse outcomes from lower limb bypass procedures in ethnic minority populations. Limited nationwide data are available from ethnic minority populations from Europe. The aim of this study is to investigate outcomes from lower limb bypass procedures in ethnic minorities from England.

METHODS: We enquired the “Hospital Episode Statistics” database, using ICD-10 codes to identify all cases of femoral-popliteal bypass operations from English NHS Hospitals from 01/01/2006 to 31/12/2015. Every case was followed up for 2 years for subsequent events. The primary outcomes were mortality and major leg amputation. Patients were broadly categorised according to Black, Asian and White ethnicity. Chi-square test was used to the ethnic groups and odds ratios (OR) were calculated using White ethnic group with the largest numbers of participants as a reference category.

RESULTS: In the examined 10-year period, 20825 femoral-popliteal bypass procedures (250 of Black, 167 of Asian, and 20.408 of White ethnicity) were recorded. Thirty-day and 2-year mortality were 2.8% and 16.8% with no significant ethnic differences. Patients of Black ethnicity had higher risk of limb loss compared to Whites (23.2% vs 15.6%, OR =1.63, 95% confidence interval (CI) 1.21-2.19, p<0.01). There was no significant difference in amputation rates between Asians and Whites (16.2% vs 15.6%, p=0.94).

CONCLUSION: Patients of Black ethnicity are at higher risk of limb loss after a femoropopliteal bypass procedure. Further research is needed to identify the causes of this discrepancy.

PMID:33951529 | DOI:10.1016/j.avsg.2021.04.018

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Aortic neck IFU violations during EVAR for ruptured infrarenal aortic aneurysms are associated with increased in-hospital mortality

Ann Vasc Surg. 2021 May 2:S0890-5096(21)00370-8. doi: 10.1016/j.avsg.2021.04.019. Online ahead of print.

ABSTRACT

OBJECTIVE: Vascular surgeons treating patients with ruptured abdominal aortic aneurysm (rAAA) must make rapid treatment decisions and sometimes lack immediate access to endovascular devices meeting the anatomic specifications of the patient at hand. We hypothesized that endovascular treatment of rAAA (rEVAR) outside manufacturer instructions-for-use (IFU) guidelines would have similar in-hospital mortality compared to patients treated on-IFU or with an infrarenal clamp during open repair (rOAR).

METHODS: Vascular Quality Initiative (VQI) datasets for endovascular and open aortic repair were queried for patients presenting with ruptured infrarenal AAA between 2013-2018. Graft-specific IFU criteria were correlated with case-specific proximal neck dimension data to classify rEVAR cases as on- or off-IFU. Univariate comparisons between the on- and off-IFU groups were performed for demographic, operative and in-hospital outcome variables. To investigate mortality differences between rEVAR and rOAR approaches, coarsened exact matching was used to match patients receiving off-IFU rEVAR with those receiving complex rEVAR (requiring at least one visceral stent or scallop) or rOAR with infrarenal, suprarenal or supraceliac clamps. A multivariable logistic regression was used to identify factors independently associated with in-hospital mortality.

RESULTS: 621 patients were treated with rEVAR, with 65% classified as on-IFU and 35% off-IFU. The off-IFU group was more frequently female (25% vs. 18%, p=0.05) and had larger aneurysms (76 vs. 72 mm, p=0.01) but otherwise was not statistically different from the on-IFU cohort. In-hospital mortality was significantly higher in patients treated off-IFU vs. on-IFU (22% vs 14%, p=0.02). Off-IFU rEVAR was associated with longer operative times (135 min vs 120 min, p=0.004) and increased intraoperative blood product utilization (2 units vs. 1 unit, p=0.002). When off-IFU patients were matched to complex rEVAR and rOAR patients, no baseline differences were found between the groups. Overall in-hospital complications associated with off-IFU were reduced compared to more complex strategies (43% vs. 60-81%, p<0.001) and in-hospital mortality was significantly lower for off-IFU rEVAR patients compared to the supraceliac clamp group (18% vs 38%, p=0.006). However, there was no significantly increased mortality associated with complex rEVAR, infrarenal rOAR or suprarenal rOAR compared to off-IFU rEVAR (all P>0.05). This finding persisted in a multivariate logistic regression.

CONCLUSIONS: Off-IFU rEVAR yields inferior in-hospital survival compared to on-IFU rEVAR but remains associated with reduced in-hospital complications when compared with more complex repair strategies. When compared with matched patients undergoing rOAR with an infrarenal or suprarenal clamp, survival was no different from off-IFU rEVAR. Taken together with the growing available evidence suggesting reduced long-term durability of off-IFU EVAR, these data suggest that a patient’s comorbidity burden should be key in making the decision to pursue off-IFU rEVAR over a more complex repair when proximal neck violations are anticipated preoperatively.

PMID:33951521 | DOI:10.1016/j.avsg.2021.04.019

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Relevance of gastrointestinal manifestations in a large Spanish cohort of patients with systemic lupus erythematosus: what do we know?

Rheumatology (Oxford). 2021 May 5:keab401. doi: 10.1093/rheumatology/keab401. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in more than 50% of SLE patients.

AIMS: To describe the GI manifestations of SLE in the RELESSER (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology) cohort and to determine if these are associated with a more severe disease, damage accrual and a worse prognosis.

METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients who fulfill ≥ 4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease.

RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI. The presence of oral ulcers reduced risk of developing damage in 33% of patients.

CONCLUSIONS: Having GI damage is associated with a worse prognosis. Patients on high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

PMID:33950249 | DOI:10.1093/rheumatology/keab401

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Focus on Survival Analysis for Eye Research

Invest Ophthalmol Vis Sci. 2021 May 3;62(6):7. doi: 10.1167/iovs.62.6.7.

ABSTRACT

Analysis of time-to-event data, otherwise known as survival analysis, is a common investigative tool in ophthalmic research. For example, time-to-event data is useful when researchers are interested in investigating how long it takes for an ocular condition to worsen or whether treatment can delay the development of a potentially vision-threatening complication. Its implementation requires a different set of statistical tools compared to those required for analyses of other continuous and categorial outcomes. In this installment of the Focus on Data series, we present an overview of selected concepts relating to analysis of time-to-event data in eye research. We introduce censoring, model selection, consideration of model assumptions, and best practice for reporting. We also consider challenges that commonly arise when analyzing time-to-event data in ophthalmic research, including collection of data from two eyes per person and the presence of multiple outcomes of interest. The concepts are illustrated using data from the Laser Intervention in Early Stages of Age-Related Macular Degeneration study and statistical computing code for Stata is provided to demonstrate the application of the statistical methods to illustrative data.

PMID:33950248 | DOI:10.1167/iovs.62.6.7

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Motor and cognitive outcomes of cerebello-spinal stimulation in neurodegenerative ataxia

Brain. 2021 May 5:awab157. doi: 10.1093/brain/awab157. Online ahead of print.

ABSTRACT

Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks, with a 14-week (T3), 24-week (T4), 36-week (T5) and 52-week follow-up (T6) (open-label phase). At each time point, a clinical, neuropsychological and neurophysiological evaluation was performed. Cerebellar-motor cortex connectivity was evaluated using transcranial magnetic stimulation (TMS). We observed a significant improvement in all motor scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale), in cognition (evaluated with the cerebellar cognitive affective syndrome scale), in quality-of-life scores, in motor cortex excitability and in cerebellar inhibition after real tDCS compared to sham stimulation and compared to baseline (T0), both at short and long-term. We observed an addon-effect after two repeated treatments with real tDCS compared to a single treatment with real tDCS. The improvement at motor and cognitive scores correlated with the restoration of cerebellar inhibition evaluated with TMS. Cerebello-spinal tDCS represents a promising therapeutic approach for both motor and cognitive symptoms in patients with neurodegenerative ataxia, a still orphan disorder of any pharmacological intervention.

PMID:33950222 | DOI:10.1093/brain/awab157

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Fundamental gene network rewiring at the second order within and across mammalian systems

Bioinformatics. 2021 May 5:btab240. doi: 10.1093/bioinformatics/btab240. Online ahead of print.

ABSTRACT

MOTIVATION: Genetic or epigenetic events can rewire molecular networks to induce extraordinary phenotypical divergences. Among the many network rewiring approaches, no model-free statistical methods can differentiate gene-gene pattern changes not attributed to marginal changes. This may obscure fundamental rewiring from superficial changes.

RESULTS: Here we introduce a model-free Sharma-Song test to determine if patterns differ in the second order, meaning that the deviation of the joint distribution from the product of marginal distributions is unequal across conditions. We prove an asymptotic chi-squared null distribution for the test statistic. Simulation studies demonstrate its advantage over alternative methods in detecting second-order differential patterns. Applying the test on three independent mammalian developmental transcriptome datasets, we report a lower frequency of co-expression network rewiring between human and mouse for the same tissue group than the frequency of rewiring between tissue groups within the same species. We also find secondorder differential patterns between microRNA promoters and genes contrasting cerebellum and liver development in mice. These patterns are enriched in the spliceosome pathway regulating tissue specificity. Complementary to previous mammalian comparative studies mostly driven by first-order effects, our findings contribute an understanding of system-wide second-order gene network rewiring within and across mammalian systems. Second-order differential patterns constitute evidence for fundamentally rewired biological circuitry due to evolution, environment, or disease.

AVAILABILITY: The generic Sharma-Song test is available from the R package ‘DiffXTables’ at https://cran.rproject.org/package=DiffXTables. Other code and data are described in Methods.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:33950233 | DOI:10.1093/bioinformatics/btab240