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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

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Prevalence and patterns of adverse events following childhood immunization and the responses of mothers in Ile-Ife, South West Nigeria: a facility-based cross-sectional survey

Osong Public Health Res Perspect. 2023 Aug;14(4):291-299. doi: 10.24171/j.phrp.2023.0071. Epub 2023 Jul 27.

ABSTRACT

BACKGROUND: This study aimed to examine the prevalence and pattern of adverse events following childhood immunization and the responses of mothers in Ile-Ife, South West Nigeria.

METHODS: This descriptive cross-sectional study was conducted among 422 mothers of children aged 0 to 24 months attending any of the 3 leading immunization clinics in Ile-Ife, Nigeria. The respondents were selected using the multi-stage sampling technique. Data were collected using a pretested structured interviewer-administered questionnaire and analyzed using IBM SPSS ver. 26.0. The chi-square test was used to test associations, while binary logistic regression was used to determine the predictors of mothers’ responses to adverse events following immunization (AEFIs). A p-value of <0.05 was considered statistically significant.

RESULTS: The mean age of the respondents was 29.99±5.74 years. About 38% of the children had experienced an AEFI. Most mothers believed that the pentavalent vaccine was the most common cause of AEFIs (67.5%). Fever (88.0%) and pain and swelling (76.0%) were the most common AEFIs. More than half of the mothers (53.7%) administered home treatment following an AEFI. Younger mothers (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.20-5.01), mothers who delivered their children at a healthcare facility (OR, 3.24; 95% CI, 1.08-9.69), and mothers who were knowledgeable about reporting AEFIs (OR, 2.53; 95% CI, 1.04-7.70) were most likely to respond appropriately to AEFIs.

CONCLUSION: The proportion of mothers who responded poorly to AEFIs experienced by their children was significant. Therefore, strategies should be implemented to improve mothers’ knowledge about AEFIs to improve their responses.

PMID:37652684 | DOI:10.24171/j.phrp.2023.0071

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Risk factors for transmission in a COVID-19 cluster infection in a high school in the Republic of Korea

Osong Public Health Res Perspect. 2023 Aug;14(4):252-262. doi: 10.24171/j.phrp.2023.0125. Epub 2023 Jul 27.

ABSTRACT

BACKGROUND: This study aimed to examine the scale, characteristics, risk factors, and modes of transmission in a coronavirus disease 2019 (COVID-19) outbreak at a high school in Seoul, Republic of Korea.

METHODS: An epidemiological survey was conducted of 1,118 confirmed cases and close contacts from a COVID-19 outbreak at an educational facility starting on May 31, 2021. In-depth interviews, online questionnaires, flow evaluations, and CCTV analyses were used to devise infection prevention measures. Behavioral and spatial risk factors were identified, and statistical significance was tested.

RESULTS: Among 3rd-year students, there were 33 confirmed COVID-19 cases (9.6%). Students who used a study room in the annex building showed a statistically significant 4.3-fold elevation in their relative risk for infection compared to those who did not use the study room. Moreover, CCTV facial recognition analysis confirmed that 17.8% of 3rd-year students did not wear masks and had the lowest percentage of mask-wearers by grade. The air epidemiological survey conducted in the study room in the annex, which met the 3 criteria for a closed space, confirmed that there was only 10% natural ventilation due to the poor ventilation system.

CONCLUSION: To prevent and manage the spread of COVID-19 in educational facilities, advance measures that consider the size, operation, and resources of each school are crucial. In addition, various survey methodologies should be used in future studies to quickly analyze a wider range of data that can inform an evidence-based quarantine response.

PMID:37652680 | DOI:10.24171/j.phrp.2023.0125

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Endoluminal radiofrequency ablation in patients with malignant biliary obstruction: a randomised trial

Gut. 2023 Aug 31:gutjnl-2023-329700. doi: 10.1136/gutjnl-2023-329700. Online ahead of print.

ABSTRACT

BACKGROUND: Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique.

DESIGN: In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280).

RESULTS: A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups.

CONCLUSION: A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction.

TRIAL REGISTRATION NUMBER: NCT03166436.

PMID:37652677 | DOI:10.1136/gutjnl-2023-329700

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Oxidative stress and early mortality in acute ischemic stroke: A prospective cohort study

Neurol Res. 2023 Aug 31:1-8. doi: 10.1080/01616412.2023.2252284. Online ahead of print.

ABSTRACT

BACKGROUND: Malondialdehyde (MDA) is an oxidative stress biomarker, which represents a unifying mechanism of brain injury that occurs throughout the ischemic stroke cascade. The current study aimed to examine whether or not acute ischemic stroke (AIS) patients who had elevated serum MDA levels at admission had an increased risk of mortality and a worse functional outcome three months later.

METHODS: An observational, prospective cohort study that enrolled 90 patients with AIS. The patients were examined in the first 24 hours and then followed up for three months to assess mortality, short-term neurological functional outcome, and neurological disability by the Modified Rankin Scale (MRS).

RESULTS: The mean of serum MDA level among AIS patients was 6.3 ± 3.7 nmol/ml. Non-survivor cases were associated with statistically significantly higher serum MDA levels compared to survivors (9.7 ± 4.3 vs. 5.3 ± 2.8, p < 0.001), respectively. Patients with severe stroke, according to NIHSS score, were associated with significantly (p < 0.05) higher MDA levels compared to moderate and mild cases (7.4 ± 4.3 vs. 5.4 ± 2.6 vs. 3.3 ± .6). At a cutoff point of ≥ 6.7 nmol/ml, the area under the curve (AUC) for serum MDA levels as a predictor of mortality was 0.8 (0.69-0.91; p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value were 77%, 80%, 89.5%, and 48.5%, respectively. Multivariate regression demonstrated that MDA level was a significant independent predictor of mortality among patients with AIS (OR = 1.29, 95% CI: 1.01 to 1.65; p = 0.041).

CONCLUSION: MDA serum level was significantly higher in non-survivors than in survivors patients, so MDA could be used as a predictor for early mortality and short-term outcome of cases with AIS.

PMID:37652662 | DOI:10.1080/01616412.2023.2252284