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Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy

Mov Disord. 2023 Sep 1. doi: 10.1002/mds.29581. Online ahead of print.

ABSTRACT

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson’s syndrome (PSP-RS).

OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice.

METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern.

RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample.

CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:37655363 | DOI:10.1002/mds.29581

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Serum homocysteine level in newly diagnosed young patients with abnormal glucose tolerance

SAGE Open Med. 2023 Aug 27;11:20503121231195602. doi: 10.1177/20503121231195602. eCollection 2023.

ABSTRACT

BACKGROUND: Hyperhomocysteinemia is an emerging risk factor causing early-onset cardiovascular events. The objective of the study was to assess serum homocysteine levels in newly diagnosed young persons (age < 30 years) with abnormal glucose tolerance.

METHODOLOGY: This cross-sectional study included 40 young participants with newly diagnosed abnormal glucose tolerance (including prediabetes and diabetes mellitus) and an equal number of young persons with normal glucose tolerance (normal glucose tolerance vs prediabetes vs. diabetes mellitus-age (years): 25.0 (22.0, 28.0) vs 25.50 (21.50, 27.0) vs 28.0 (25.0, 29.0), median (interquartile range)). Glycemic status was diagnosed by American Diabetes Association, 2021 criteria. After taking clinical information, fasting blood was collected to measure homocysteine by chemiluminescent immunoassay.

RESULTS: Homocysteine level was different across the spectrum of glycemic status (normal glucose tolerance vs. prediabetes vs. diabetes mellitus: 15.57 (13.89-20.71) vs 13.19 (11.40-18.11) vs 12.27 (9.97-14.42) µmol/L; median (interquartile range); p = 0.006). Serum homocysteine was significantly elevated in participants with normal glucose tolerance than diabetes mellitus (p = 0.006) but statistically similar in prediabetes in comparison to both normal glucose tolerance and diabetes mellitus (p = NS for both). Homocysteine level was above the normal level in 47.5% of participants with normal glucose tolerance and in 22.5% with abnormal glucose tolerance (p = 0.019).

CONCLUSIONS: Patients under 30 years with diabetes mellitus had lower homocysteine levels than those with normal glucose tolerance.

PMID:37655304 | PMC:PMC10467175 | DOI:10.1177/20503121231195602

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Hygienic practice during complementary feeding and its associated factors among mothers/caregivers of children aged 6-24 months in Wolaita Sodo town, southern Ethiopia

SAGE Open Med. 2023 Aug 24;11:20503121231195416. doi: 10.1177/20503121231195416. eCollection 2023.

ABSTRACT

INTRODUCTION: Complementary feeding is an important stage in a child’s development as it provides the necessary nutrients for optimal growth and development. However, improper handling, storage, and preparation of complementary foods can result in contamination by microorganisms, leading to foodborne illnesses and malnutrition. Therefore, this study aimed to determine hygienic practices during complementary feeding and associated factors among mothers of children aged 6-24 months in Wolaita Sodo town, southern Ethiopia.

METHODS: A community-based, cross-sectional study was undertaken among mothers/caregivers of children aged 6-24 months from December 1-30, 2022. A total of 602 participants were recruited using a simple random sampling procedure. The hygienic practice of complementary feeding was assessed based on a related seven items questionnaire (Cronbach’s alpha 0.72). Data were entered into Epi-data version 4.6 and analyzed using Statistical Package for Social Science version 26. Multivariable binary logistic regression was used to identify the statistically significant factors associated with proper hygienic practice of complementary feeding. Variables with a p-value of <0.05 in the multivariable logistic regression analysis model were considered statistically significant.

RESULTS: The study indicated that 42.0%, (95% confidence interval (CI): 38, 45.8) of the mothers/caregivers of children aged 6-24 months had proper hygienic practices during complementary feeding. Mothers who could read and write (adjusted odd ratio (AOR): 3.36, 95% CI (1.53, 7.41)) and those who had completed primary school (AOR: 1.7, 95% CI (1.02, 2.85)), media exposure (AOR: 3.38, 95% CI (2.1, 5.4)), and attitude toward hygienic practice (AOR: 3.29, 95% CI (2.2, 4.91)) were independent predictors of hygiene practices during complementary feeding.

CONCLUSION: This study found that the prevalence of hygiene practices during complementary feeding was relatively low. Being educated, access to media, and positive attitudes toward hygienic practices were predicting factors. As a result, strengthening training and counseling services for mothers regarding complementary feeding and processing is recommended.

PMID:37655302 | PMC:PMC10467249 | DOI:10.1177/20503121231195416

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Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) against Mycobacterium abscessus

Front Cell Infect Microbiol. 2023 Aug 15;13:1225341. doi: 10.3389/fcimb.2023.1225341. eCollection 2023.

ABSTRACT

OBJECTIVE: To evaluate contezolid (MRX-I) antibacterial activity against Mycobacterium abscessus in vitro and in vivo and to assess whether MRX-I treatment can prolong survival of infected zebrafish.

METHODS: MRX-I inhibitory activity against M. abscessus in vitro was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled M. abscessus. Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on M. abscessus growth inhibition using one-way ANOVA. Linear trend analysis of CFU counts and fluorescence intensities (mean ± SE values) was performed to detect linear relationships between MRX-I, AZM and LZD concentrations and these parameters.

RESULTS: MRX-I anti-M. abscessus minimum inhibitory concentration (MIC) and MTC were 16 μg/mL and 15.6 μg/mL, respectively. MRX-I MTC-treated zebrafish fluorescence intensities were significantly lower than respective LZD group intensities (whole-body: 439040 ± 3647 vs. 509184 ± 23064, p < 0.01); head: 74147 ± 2175 vs. 95996 ± 8054, p < 0.05). As MRX-I concentration was increased from 0.488 μg/mL to 15.6 μg/mL, zebrafish whole-body, head and heart fluorescence intensities decreased. Statistically insignificant differences between the MRX-I MTC group survival rate (78.33%) vs. corresponding rates of the 62.5 μg/mL-treated AZM MTC group (88.33%, p > 0.05) and the 15.6 μg/mL-treated LZD MTC group (76.67%, p > 0.05) were observed.

CONCLUSION: MRX-I effectively inhibited M. abscessus growth and prolonged zebrafish survival when administered to M. abscessus-infected zebrafish, thus demonstrating that MRX-I holds promise as a clinical treatment for human M. abscessus infections.

PMID:37655300 | PMC:PMC10465794 | DOI:10.3389/fcimb.2023.1225341

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Utilizing metagenomic next-generation sequencing for diagnosis and lung microbiome probing of pediatric pneumonia through bronchoalveolar lavage fluid in pediatric intensive care unit: results from a large real-world cohort

Front Cell Infect Microbiol. 2023 Aug 15;13:1200806. doi: 10.3389/fcimb.2023.1200806. eCollection 2023.

ABSTRACT

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples.

METHODS: A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients’ lung BALF microbiomes were explored using the mNGS data.

RESULTS: Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%).

CONCLUSIONS: mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.

PMID:37655299 | PMC:PMC10466250 | DOI:10.3389/fcimb.2023.1200806

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Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review

Orthop J Sports Med. 2023 Aug 21;11(8):23259671231187894. doi: 10.1177/23259671231187894. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results.

PURPOSE: To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA.

STUDY DESIGN: Systematic review.

METHODS: RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size.

RESULTS: Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively.

CONCLUSION: Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.

PMID:37655254 | PMC:PMC10467394 | DOI:10.1177/23259671231187894

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GP speciality trainees’ knowledge and values towards physical activity: a national survey of Scottish trainees

BJGP Open. 2023 Aug 31:BJGPO.2023.0051. doi: 10.3399/BJGPO.2023.0051. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the known benefits of physical activity (PA), one third of adults in the UK fail to meet recommended levels of PA. PA promotion in primary care has been shown to be effective at improving PA in patients but implementation of PA promotion by GPs remains poor. Research has shown a need to improve PA education in undergraduate medical education, but no review of postgraduate medical education has been performed.

AIM: Assess the knowledge and values towards PA promotion in General Practice specialist trainees (GPST) in Scotland.

DESIGN & SETTING: Cross-sectional survey distributed to GPSTs trainees in Scotland.

METHOD: A mixed methods cross-sectional survey, informed by previous research, was developed, and distributed, to all (n = 1205) GPSTs in Scotland in December 2022. Descriptive statistics were used to analysis quantitative data. A content analysis of free text responses was also performed.

RESULTS: A total of 168 GPSTs responded, representing 13.4% of all GPSTs in Scotland. Of respondents, 93.5% reported no previous experience in Sports and Exercise Science/Medicine. Overall, 38.9% of respondents stated they were unaware of the current UK PA guidelines, with 33.9% unable to correctly identify the UK PA guidelines when presented with multiple choice options. 83% felt they had been inadequately trained to deliver PA advice during their medical training.

CONCLUSION: This study highlights a lack of knowledge, confidence, and education in PA promotion in GPSTs in Scotland. Given the importance of primary prevention, this urgently needs to be addressed.

PMID:37652716 | DOI:10.3399/BJGPO.2023.0051

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Quantitative Systems Pharmacology & Machine Learning – A match made in heaven or hell?

J Pharmacol Exp Ther. 2023 Aug 31:JPET-MR-2022-001551. doi: 10.1124/jpet.122.001551. Online ahead of print.

ABSTRACT

As pharmaceutical development moves from early stage in vitro experimentation to later in vivo and subsequent clinical trials, data and knowledge are acquired across multiple time and length scales, from the subcellular to whole patient cohort scale. Realising the potential of this data for informing decision making in pharmaceutical development requires the individual and combined application of machine learning (ML) and mechanistic multiscale mathematical modelling approaches. Here we outline how these two approaches, both individually and in tandem, can be applied at different stages of the drug discovery and development pipeline to inform decision making compound development. The importance of discerning between knowledge and data is highlighted in informing the initial use of ML or mechanistic Quantitative Systems Pharmacology (QSP) models. We discuss the application of sensitivity and structural identifiability analyses of QSP models in informing future experimental studies, to which ML may be applied, as well as how ML approaches can be used to inform mechanistic model development. Relevant literature studies are highlighted and we close by discussing caveats regarding the application of each approach in an age of constant data acquisition. Significance Statement We consider when best to apply Machine Learning (ML) and mechanistic Quantitative Systems Pharmacology (QSP) approaches in the context of the drug discovery and development pipeline. We discuss the importance of prior knowledge and data available for the system of interest and how this informs the individual and combined application of ML and QSP approaches at each stage of the pipeline.

PMID:37652709 | DOI:10.1124/jpet.122.001551

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Trends of legionellosis reported in Jeju Province, Republic of Korea, 2015-2022

Osong Public Health Res Perspect. 2023 Aug;14(4):321-327. doi: 10.24171/j.phrp.2023.0145. Epub 2023 Aug 21.

ABSTRACT

BACKGROUND: The number of reported cases of Legionnaires’ disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province than the previous national peak. A descriptive epidemiological study was conducted to analyze trends in the incidence of reported LD cases in Jeju Island from 2015 to 2022.

METHODS: The data for this study were obtained from case reports submitted to the Korea Disease Control and Prevention Agency through its Disease and Health Integrated Management System. The selection criteria were cases or suspected cases of LD reported among Jeju residents between 2015 and 2022. The 95% confidence interval of the crude incidence rate was calculated using the Poisson distribution.

RESULTS: Since 2020, the incidence rate of LD in Jeju has risen sharply, showing a statistically significant difference from the national incidence rate. A particular medical institution in Jeju reported a significant number of LD cases. Screening with the urine antigen test (UAT) also increased significantly.

CONCLUSION: Our findings indicate that the rapid increase in cases of LD in Jeju Province since 2020 was due to the characteristics of medical-care use among Jeju residents, which were focused on a specific medical institution. According to their clinical practice guidelines, this medical institution conducted UATs to screen patients suspected of pneumonia.

PMID:37652687 | DOI:10.24171/j.phrp.2023.0145

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Epidemiological characteristics of carbapenemase-producing Enterobacteriaceae outbreaks in the Republic of Korea between 2017 and 2022

Osong Public Health Res Perspect. 2023 Aug;14(4):312-320. doi: 10.24171/j.phrp.2023.0069. Epub 2023 Aug 21.

ABSTRACT

BACKGROUND: We aimed to describe the epidemiological characteristics of carbapenemase-producing Enterobacteriaceae (CPE) outbreaks in healthcare settings in the Republic of Korea between 2017 and 2022.

METHODS: Under the national notifiable disease surveillance system, we obtained annual descriptive statistics regarding the isolated species, carbapenemase genotype, healthcare facility type, outbreak location and duration, and number of patients affected and recommended interventions. We used epidemiological investigation reports on CPE outbreaks reported to Korea Disease Control and Prevention Agency from June 2017 to September 2022.

RESULTS: Among the 168 reports analyzed, Klebsiella pneumoniae (85.1%) was the most frequently reported species, while K. pneumoniae carbapenemase (KPC, 82.7%) was the most common carbapenemase genotype. Both categories increased from 2017 to 2022 (p<0.01). General hospitals had the highest proportion (54.8%), while tertiary general hospitals demonstrated a decreasing trend (p<0.01). The largest proportion of outbreaks occurred exclusively in intensive care units (ICUs, 44.0%), and the frequency of concurrent outbreaks in ICUs and general wards increased over time (p<0.01). The median outbreak duration rose from 43.5 days before the coronavirus disease 2019 (COVID-19) pandemic (2017-2019) to 79.5 days during the pandemic (2020-2022) (p=0.01), and the median number of patients associated with each outbreak increased from 5.0 to 6.0 (p=0.03). Frequently recommended interventions included employee education (38.1%), and 3 or more measures were proposed for 45.2% of outbreaks.

CONCLUSION: In the Republic of Korea, CPE outbreaks have been consistently dominated by K. pneumoniae and KPC. The size of these outbreaks increased during the COVID-19 pandemic. Our findings highlight the need for continuing efforts to control CPE outbreaks using a multimodal approach, while considering their epidemiology.

PMID:37652686 | DOI:10.24171/j.phrp.2023.0069