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Nevin Manimala Statistics

Mechanical Thrombectomy in Acute Stroke Patients with Moderate to Severe Pre-Stroke Disability

J Stroke. 2022 Sep;24(3):396-403. doi: 10.5853/jos.2022.00906. Epub 2022 Sep 30.

ABSTRACT

BACKGROUND AND PURPOSE: Studies on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with preexisting disability are limited. We aimed to compare the outcomes of MT versus best medical treatment (BMT) in these patients.

METHODS: In the nationwide Austrian registry and Swiss monocentric registry, we identified 462 AIS patients with pre-stroke disability (modified Rankin Scale [mRS] score ≥3) and acute large vessel occlusion. The primary outcome was returning to pre-stroke mRS or better at 3 months. Secondary outcomes were early neurological improvement (National Institutes of Health Stroke Scale score improvement ≥8 at 24 to 48 hours), 3-month mortality, and symptomatic intracerebral hemorrhage (sICH). Multivariable regression models and propensity score matching (PSM) were used for statistical analyses.

RESULTS: Compared with the BMT group (n=175), the MT group (n=175) had younger age, more severe strokes, and lower pre-stroke mRS, but similar proportion of receiving intravenous thrombolysis. MT was associated with higher odds of returning to baseline mRS or better at 3 months (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.39 to 4.47), early neurological improvement (aOR, 2.62; 95% CI, 1.41 to 4.88), and lower risk of 3-month mortality (aOR, 0.29; 95% CI, 0.18 to 0.49). PSM analysis showed similar findings. MT was not associated with an increased risk of sICH (4.0% vs. 2.1% in all patients; 4.2% vs. 2.4% in the PSM cohort).

CONCLUSIONS: MT in patients with pre-stroke mRS ≥3 might improve the 3-month outcomes and short-term neurological impairment, suggesting that pre-stroke disability alone should not be a reason to withhold MT, but that individual case-by-case decisions may be more appropriate.

PMID:36221943 | DOI:10.5853/jos.2022.00906

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Nevin Manimala Statistics

Detection and differentiation of semi-transparent materials simulating biological structures using optical coherence tomography: a phantom study

J Biomed Opt. 2022 Oct;27(10). doi: 10.1117/1.JBO.27.10.100501.

ABSTRACT

SignificanceLymphatic and peripheral nervous system imaging is of prime importance for monitoring various important pathologic processes including cancer development and metastasis, and response to therapy.AimOptical coherence tomography (OCT) is a promising approach for this imaging task but is challenged by the near-transparent nature of these structures. Our aim is to detect and differentiate semi-transparent materials using OCT texture analysis, toward label-free neurography and lymphography.ApproachWe have recently demonstrated an innovative OCT texture analysis-based approach that used speckle statistics to image lymphatics and nerves in-vivo that does not rely on negative contrast. However, these two near-transparent structures could not be easily differentiated from each other in the texture analysis parameter space. Here, we perform a rigorous follow-up study to improve upon this differentiation in controlled phantoms mimicking the optical properties of these tissues.ResultsThe results of the three-parameter Rayleigh distribution fit to the OCT images of six types of tissue-mimicking materials varying in transparency and biophysical properties demonstrate clear differences between them, suggesting routes for improved lymphatics-nerves differentiation.ConclusionsWe demonstrate a novel OCT texture analysis-based lymphatics-nerves differentiation methodology in tissue-simulating phantoms. Future work will focus on longitudinal in-vivo lymphangiography and neurography in response to cancer therapeutics toward adaptive personalized medicine.

PMID:36221173 | DOI:10.1117/1.JBO.27.10.100501

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Nevin Manimala Statistics

Letter: fighting the battle but losing the war-inflammatory bowel disease and venous thromboembolism

Aliment Pharmacol Ther. 2022 Nov;56(9):1425-1426. doi: 10.1111/apt.17203.

NO ABSTRACT

PMID:36221159 | DOI:10.1111/apt.17203

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Nevin Manimala Statistics

Mimicking platelet indices in patients with malaria and dengue hemorrhagic fever: characteristics and clinical applications

Trop Med Health. 2022 Oct 11;50(1):76. doi: 10.1186/s41182-022-00467-8.

ABSTRACT

BACKGROUND: Although platelet indices are routinely available using automated blood cell counters, the clinical applications of these parameters for malaria and dengue hemorrhagic fever (DHF) have not been substantially implemented. We conducted this study to investigate the potential role of platelet indices as a prognostic marker in adult patients with Plasmodium vivax malaria, Plasmodium falciparum malaria, and DHF admitted to the Hospital for Tropical Diseases, Bangkok, Thailand.

METHODS: We enrolled 219 eligible patients, comprising 96 with P. falciparum malaria, 71 with P. vivax malaria, and 52 with DHF. We evaluated the study groups’ baseline clinical features and alterations of platelet indices during the first 4 days of admission.

RESULTS: Upon admission, the initial laboratory findings showed no statistically significant difference in platelet count (PC), plateletcrit (PCT), or platelet distribution width (PDW) between patients with P. vivax and P. falciparum; however, mean platelet volume (MPV) was significantly higher in patients with P. falciparum. Comparisons of the initial platelet indices in malaria and DHF showed that only PC and PCT were significantly lower in DHF. Although MPV in DHF tended to be lower than in malaria, a statistically significant difference was observed only with P. falciparum. Moreover, the results also showed no significant alterations in the platelet indices among the study groups during the first 4 days of admission.

CONCLUSIONS AND RECOMMENDATIONS: Clinical presentations of DHF and malaria are nonspecific and may overlap with other common tropical diseases. Alterations of initial platelet indices may be investigated in P. vivax and P. falciparum malaria mimicking DHF. Although a significant reduction in PC and PCT in DHF might be a clue for differential diagnosis of malaria, the use of MPV and PDW might be impractical. We suggest that appropriate laboratory diagnoses for malaria and dengue infections are still needed for the differential diagnosis of acute febrile patients who have a risk of malaria or dengue infections. To clarify the clinical utility of platelet indices in patients with dengue and malaria, further studies are required that particularly include patients with different severities, geographical areas, and levels of health care settings.

PMID:36221147 | DOI:10.1186/s41182-022-00467-8

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Nevin Manimala Statistics

SARS-CoV-2 seroprevalence and infection rate in Manila, Philippines prior to national vaccination program implementation: a repeated cross-sectional analysis

Trop Med Health. 2022 Oct 11;50(1):75. doi: 10.1186/s41182-022-00468-7.

ABSTRACT

BACKGROUND: SARS-CoV-2 seroepidemiological studies are used to guide public health decision making and to prepare for emerging infectious diseases. Disease occurrence estimates are limited in the Philippines, the country with the highest reported number of coronavirus disease-related deaths in the Western Pacific region. We aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila prior to the implementation of the national coronavirus disease vaccination program.

METHODS: We conducted repeated cross-sectional surveys at the animal bite clinic in San Lazaro Hospital, Manila, the Philippines across four periods, 3 months apart, between May 2020 and March 2021. Multivariable logistic regression was used to assess associations between different characteristics and infection status including seropositivity.

RESULTS: In total 615 participants were enrolled, ranging from 115 to 174 per period. Seroprevalence quadrupled between the first (11.3%) and second (46.8%) periods and plateaued thereafter (third-46.0%, fourth-44.6%). Among seropositive participants, total antibody concentration was comparable throughout the first to third periods but declined between the third and fourth periods. Infection prevalence was comparable across enrollment periods (range 2.9-9.5%). Post-secondary education [aOR 0.42 (95% CI 0.26, 0.67)] was protective, and frontline work [aOR 1.81 (95% CI 1.18, 2.80)] was associated with increased odds of seropositivity. Frontline work status [aOR 2.27 (95% CI 1.10, 4.75)] and large household size [aOR 2.45 (95% CI 1.18, 5.49)] were associated with increased odds of infection.

CONCLUSIONS: The quadrupling of seroprevalence over 3 months between the first and second enrollment periods coincided with the high burden of infection in Metro Manila in early 2020. Our findings suggest a limit to the rise and potential decline of population-level SARS-CoV-2 infection-induced immunity without introduction of vaccines. These results may add to our understanding of how immunity develops against emerging infectious diseases including coronaviruses.

PMID:36221142 | DOI:10.1186/s41182-022-00468-7

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Nevin Manimala Statistics

PCA outperforms popular hidden variable inference methods for molecular QTL mapping

Genome Biol. 2022 Oct 11;23(1):210. doi: 10.1186/s13059-022-02761-4.

ABSTRACT

BACKGROUND: Estimating and accounting for hidden variables is widely practiced as an important step in molecular quantitative trait locus (molecular QTL, henceforth “QTL”) analysis for improving the power of QTL identification. However, few benchmark studies have been performed to evaluate the efficacy of the various methods developed for this purpose.

RESULTS: Here we benchmark popular hidden variable inference methods including surrogate variable analysis (SVA), probabilistic estimation of expression residuals (PEER), and hidden covariates with prior (HCP) against principal component analysis (PCA)-a well-established dimension reduction and factor discovery method-via 362 synthetic and 110 real data sets. We show that PCA not only underlies the statistical methodology behind the popular methods but is also orders of magnitude faster, better-performing, and much easier to interpret and use.

CONCLUSIONS: To help researchers use PCA in their QTL analysis, we provide an R package PCAForQTL along with a detailed guide, both of which are freely available at https://github.com/heatherjzhou/PCAForQTL . We believe that using PCA rather than SVA, PEER, or HCP will substantially improve and simplify hidden variable inference in QTL mapping as well as increase the transparency and reproducibility of QTL research.

PMID:36221136 | DOI:10.1186/s13059-022-02761-4

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Nevin Manimala Statistics

A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients

BMC Musculoskelet Disord. 2022 Oct 12;23(1):908. doi: 10.1186/s12891-022-05846-0.

ABSTRACT

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages’ function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages.

METHODS: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined.

RESULTS: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients’ macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients’ group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI).

CONCLUSION: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients’ macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients’ macrophages.

PMID:36221125 | DOI:10.1186/s12891-022-05846-0

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Nevin Manimala Statistics

Cross-watershed distribution pattern challenging the elimination of Oncomelania hupensis, the intermediate host of Schistosoma japonica, in Sichuan province, China

Parasit Vectors. 2022 Oct 11;15(1):363. doi: 10.1186/s13071-022-05496-0.

ABSTRACT

BACKGROUND: Snail control is critical to schistosomiasis control efforts in China. However, re-emergence of Oncomelania hupensis is challenging the achievements of schistosomiasis control. The present study aimed to test whether the amphibious snails can spread across watersheds using a combination of population genetics and geographic statistics.

METHODS: The digital maps and attributes of snail habitats were obtained from the national survey on O. hupensis. Snail sampling was performed in 45 counties of Sichuan Province. The cox1 gene of specimens was characterized by sequencing. Unique haplotypes were found for phylogenetic inference and mapped in a geographical information system (GIS). Barriers of gene flow were identified by Monmonier’s maximum difference algorithm. The watercourses and watersheds in the study area were determined based on a digital elevation model (DEM). Plain areas were defined by a threshold of slope. The slope of snail habitats was characterized and the nearest distance to watercourses was calculated using a GIS platform. Spatial dynamics of high-density distributions were observed by density analysis of snail habitats.

RESULTS: A total of 422 cox1 sequences of O. hupensis specimens from 45 sampling sites were obtained and collapsed into 128 unique haplotypes or 10 clades. Higher haplotype diversity in the north of the study area was observed. Four barriers to gene flow, leading to five sub-regions, were found across the study area. Four sub-regions ran across major watersheds, while high-density distributions were confined within watersheds. The result indicated that snails were able to disperse across low-density areas. A total of 63.48% habitats or 43.29% accumulated infested areas were distributed in the plain areas where the overall slope was < 0.94°. Approximately 90% of snail habitats were closer to smaller watercourses. Historically, high-density areas were mainly located in the plains, but now more were distributed in hilly region.

CONCLUSIONS: Our study showed the cross-watershed distribution of Oncomelania snails at a large scale. Natural cross-watershed spread in plains and long-distance dispersal by humans and animals might be the main driver of the observed patterns. We recommend cross-watershed joint control strategies for snail and schistosomiasis control.

PMID:36221118 | DOI:10.1186/s13071-022-05496-0

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Nevin Manimala Statistics

Managing clustering effects and learning effects in the design and analysis of randomised surgical trials: a review of existing guidance

Trials. 2022 Oct 11;23(1):869. doi: 10.1186/s13063-022-06743-6.

ABSTRACT

BACKGROUND: The complexities associated with delivering randomised surgical trials, such as clustering effects, by centre or surgeon, and surgical learning, are well known. Despite this, approaches used to manage these complexities, and opinions on these, vary. Guidance documents have been developed to support clinical trial design and reporting. This work aimed to identify and examine existing guidance and consider its relevance to clustering effects and learning curves within surgical trials.

METHODS: A review of existing guidelines, developed to inform the design and analysis of randomised controlled trials, is undertaken. Guidelines were identified using an electronic search, within the Equator Network, and by a targeted search of those endorsed by leading UK funding bodies, regulators, and medical journals. Eligible documents were compared against pre-specified key criteria to identify gaps or inconsistencies in recommendations.

RESULTS: Twenty-eight documents were eligible (12 Equator Network; 16 targeted search). Twice the number of guidance documents targeted design (n/N=20/28, 71%) than analysis (n/N=10/28, 36%). Managing clustering by centre through design was well documented. Clustering by surgeon had less coverage and contained some inconsistencies. Managing the surgical learning curve, or changes in delivery over time, through design was contained within several documents (n/N=8/28, 29%), of which one provided guidance on reporting this and restricted to early phase studies only. Methods to analyse clustering effects and learning were provided in five and four documents respectively (N=28).

CONCLUSIONS: To our knowledge, this is the first review as to the extent to which existing guidance for designing and analysing randomised surgical trials covers the management of clustering, by centre or surgeon, and the surgical learning curve. Twice the number of identified documents targeted design aspects than analysis. Most notably, no single document exists for use when designing these studies, which may lead to inconsistencies in practice. The development of a single document, with agreed principles to guide trial design and analysis across a range of realistic clinical scenarios, is needed.

PMID:36221107 | DOI:10.1186/s13063-022-06743-6

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Nevin Manimala Statistics

Does eating behaviour among adolescents and young adults seeking obesity treatment differ depending on sex, body composition, and parental country of birth?

BMC Public Health. 2022 Oct 11;22(1):1895. doi: 10.1186/s12889-022-14297-0.

ABSTRACT

BACKGROUND: Adolescents and young adults around the world experience high rates of weight gain. The underlying eating behaviours that may lead to overconsumption of energy are complex and can depend on a number of factors. The aim of this study was to explore if eating behaviour among adolescents and young adults referred to specialized obesity treatment differed depending on sex, body composition, and parental country of birth.

METHODS: Adolescents and young adults aged 16-25 years, referred for obesity treatment in 2018-2021 were included in the study. Eating behaviour was assessed using the Three Factor Eating Questionnaire, comprising domains of uncontrolled-, emotional- and cognitive restraint eating. Student’s t-test was used to compare differences in eating behaviour scores between males and females, and between those having at least one parent born in a Nordic country and those with both parents born outside the Nordic countries. Associations between BMI, waist circumference, and body fat percentage, and eating behaviour as the dependent variable, were examined using linear regression.

RESULTS: A total of 463 participants, mean age 21 years and mean BMI 41.3 kg/m2, were included in the analysis. Females scored statistically significantly higher than males on emotional eating (45.8 vs. 35.4, p = 0.002) and cognitive restraint eating (45.4 vs. 39.2, p = 0.009). Participants with at least one parent born in a Nordic country reported a statistically significantly lower score of uncontrolled eating (45.7 vs. 51.3, p = 0.02) compared to participants with both parents born outside the Nordic countries. Further, there were statistically significant inverse associations between cognitive restraint eating scores and BMI (β=-0.64, 95%CI: -0.97 to -0.31), waist circumference (β=-0.44, 95%CI: -0.61 to -0.27) and body fat percentage (β=-0.57, 95%CI: -1.01 to -0.14) in models adjusted for age, sex, smoking, and civil status.

CONCLUSION: Our findings suggest that sex and parental country of birth may influence eating behaviours among adolescents and young adults referred for specialist obesity treatment. We also found that cognitive restraint eating decreased with increasing BMI, waist circumference, and body fat percentage. This indicates that there may be an inverse association between the ability to restrain oneself from eating and gaining weight, however, the direction of the association must be investigated further. Increased knowledge about eating behaviours may be valuable in the clinical setting.

PMID:36221108 | DOI:10.1186/s12889-022-14297-0