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Nevin Manimala Statistics

Intense pulsed light plus meibomian gland expression versus intense pulsed light alone for meibomian gland dysfunction: A randomized crossover study

PLoS One. 2021 Mar 4;16(3):e0246245. doi: 10.1371/journal.pone.0246245. eCollection 2021.

ABSTRACT

PURPOSE: To investigate the comparative efficacy of intense pulsed light (IPL) therapy alone with that of IPL plus meibomian gland expression (MGX) for meibomian gland dysfunction (MGD).

METHODS: This is a prospective randomized crossover clinical trial. Sixty patients were enrolled and randomly assigned to two groups. All of patients underwent four treatment sessions in total, which were two weeks apart. Group 1 underwent two sessions of IPL therapy with MGX, as well as two sessions of IPL alone. Group 2 received two sessions of IPL therapy alone, and two sessions of IPL therapy with MGX. The following parameters were measured at baseline (BL), 2 weeks after the second treatment session (FU1), and 2 weeks after the fourth treatment session (FU2): tearfilm break-up time (BUT), Oxford grade for corneal staining, meibomian gland expressibility (MGE), meibum quality (MQ), and ocular surface disease index (OSDI). The separate effect of MGX on improvement of MGD parameters was evaluated using generalized estimating equation (GEE).

RESULTS: The mean age of the participants was 57.52 ± 10.50 years. The BUT, Oxford grade, MGE, MQ, and OSDI of both groups improved significantly (from baseline) by the end of four treatment sessions (FU2 compared to BL; all p-values <0.05). The MGE and MQ significantly improved after the first and second treatment sessions (FU1 compare to BL; all p-values < 0.001). However, the improvement was not statistically significant after the third and fourth treatment sessions (FU2 compared to FU1; p-value of 0.388 for MGE and 0.645 for MQ in group 1, 0.333 for MGE and 0.333 for MQ in group 2). The IPL plus MGX therapy produced greater improvements in the BUT scores than did IPL therapy alone (p = 0.003 by GEE). In contrast, the Oxford grade, MGE, MQ, and OSDI were not influenced by the addition of MGX to IPL (p = 0.642, 0.663, 0.731, and 0.840, respectively by GEE).

CONCLUSION: IPL therapy effectively improves the subjective symptoms and objective ocular findings of MGD. MGX enhanced the improvement of BUT driven by IPL therapy. The meibomian gland function (MGE and MQ) recovers faster in response to IPL therapy than did the other parameters.

PMID:33662017 | DOI:10.1371/journal.pone.0246245

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Nevin Manimala Statistics

The exposure risk to COVID-19 in most affected countries: A vulnerability assessment model

PLoS One. 2021 Mar 4;16(3):e0248075. doi: 10.1371/journal.pone.0248075. eCollection 2021.

ABSTRACT

The world is facing the coronavirus pandemic (COVID-19), which began in China. By August 18, 2020, the United States, Brazil, and India were the most affected countries. Health infrastructure and socioeconomic vulnerabilities may be affecting the response capacities of these countries. We compared official indicators to identify which vulnerabilities better determined the exposure risk to COVID-19 in both the most and least affected countries. To achieve this purpose, we collected indicators from the Infectious Disease Vulnerability Index (IDVI), the World Health Organization (WHO), the World Bank, and the Brazilian Geography and Statistics Institute (IBGE). All indicators were normalized to facilitate comparisons. Speed, incidence, and population were used to identify the groups of countries with the highest and lowest risks of infection. Countries’ response capacities were determined based on socioeconomic, political, and health infrastructure conditions. Vulnerabilities were identified based on the indicator sensitivity. The highest-risk group included the U.S., Brazil, and India, whereas the lowest-risk group (with the largest population by continent) consisted of China, New Zealand, and Germany. The high-sensitivity cluster had 18 indicators (50% extra IDVI), such as merchandise trade, immunization, public services, maternal mortality, life expectancy at birth, hospital beds, GINI index, adolescent fertility, governance, political stability, transparency/corruption, industry, and water supply. The greatest vulnerability of the highest-risk group was related first to economic factors (merchandise trade), followed by public health (immunization), highlighting global dependence on Chinese trade, such as protective materials, equipment, and diagnostic tests. However, domestic political factors had more indicators, beginning with high sensitivity and followed by healthcare and economic conditions, which signified a lesser capacity to guide, coordinate, and supply the population with protective measures, such as social distancing.

PMID:33662028 | DOI:10.1371/journal.pone.0248075

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Nevin Manimala Statistics

Network dynamics of momentary affect states and future course of psychopathology in adolescents

PLoS One. 2021 Mar 4;16(3):e0247458. doi: 10.1371/journal.pone.0247458. eCollection 2021.

ABSTRACT

BACKGROUND: Recent theories argue that an interplay between (i.e., network of) experiences, thoughts and affect in daily life may underlie the development of psychopathology.

OBJECTIVE: To prospectively examine whether network dynamics of everyday affect states are associated with a future course of psychopathology in adolescents at an increased risk of mental disorders.

METHODS: 159 adolescents from the East-Flanders Prospective Twin Study cohort participated in the study. At baseline, their momentary affect states were assessed using the Experience Sampling Method (ESM). The course of psychopathology was operationalized as the change in the Symptom Checklist-90 sum score after 1 year. Two groups were defined: one with a stable level (n = 81) and one with an increasing level (n = 78) of SCL-symptom severity. Group-level network dynamics of momentary positive and negative affect states were compared between groups.

RESULTS: The group with increasing symptoms showed a stronger connections between negative affect states and their higher influence on positive states, as well as higher proneness to form ‘vicious cycles’, compared to the stable group. Based on permutation tests, these differences were not statistically significant.

CONCLUSION: Although not statistically significant, some qualitative differences were observed between the networks of the two groups. More studies are needed to determine the value of momentary affect networks for predicting the course of psychopathology.

PMID:33661971 | DOI:10.1371/journal.pone.0247458

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Nevin Manimala Statistics

Data-driven CAD-CAM vs traditional total contact custom insoles: A novel quantitative-statistical framework for the evaluation of insoles offloading performance in diabetic foot

PLoS One. 2021 Mar 4;16(3):e0247915. doi: 10.1371/journal.pone.0247915. eCollection 2021.

ABSTRACT

BACKGROUND: Elevated plantar pressures represent a significant risk factor for neuropathic diabetic foot (NDF) ulceration. Foot offloading, through custom-made insoles, is essential for prevention and healing of NDF ulcerations. Objective quantitative evaluation to design custom-made insoles is not a standard method. Aims: 1) to develop a novel quantitative-statistical framework (QSF) for the evaluation and design of the insoles’ offloading performance through in-shoe pressure measurement; 2) to compare the pressure-relieving efficiency of traditional shape-based total contact customised insoles (TCCI) with a novel CAD-CAM approach by the QSF.

METHODS: We recruited 30 neuropathic diabetic patients in cross-sectional study design. The risk-regions of interest (R-ROIs) and their areas with in-shoe peak pressure statistically ≥200kPa were identified for each patients’ foot as determined on the average of peak pressure maps ascertained per each stance phase. Repeated measures Friedman test compared R-ROIs’ areas in three different walking condition: flat insole (FI); TCCI and CAD-CAM insoles.

RESULTS: As compared with FI (20.6±12.9 cm2), both the TCCI (7±8.7 cm2) and the CAD-CAM (5.5±7.3 cm2) approaches provided a reduction of R-ROIs mean areas (p<0.0001). The CAD-CAM approach performed better than the TCCI with a mean pressure reduction of 37.3 kPa (15.6%) vs FI.

CONCLUSIONS: The CAD-CAM strategy achieves better offloading performance than the traditional shape-only based approach. The introduced QSF provides a more rigorous method to the direct 200kPa cut-off approach outlined in the literature. It provides a statistically sound methodology to evaluate the offloading insoles design and subsequent monitoring steps. QSF allows the analysis of the whole foot’s plantar surface, independently from a predetermined anatomical identification/masking. QSF can provide a detailed description about how and where custom-made insole redistributes the underfoot pressure respect to the FI. Thus, its usefulness extends to the design step, helping to guide the modifications necessary to achieve optimal offloading insole performances.

PMID:33661973 | DOI:10.1371/journal.pone.0247915

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Nevin Manimala Statistics

Association of periodontitis with oral malodor in Korean adults

PLoS One. 2021 Mar 4;16(3):e0247947. doi: 10.1371/journal.pone.0247947. eCollection 2021.

ABSTRACT

This study aimed to evaluate the association of periodontitis with the organoleptic score (OLS)-defined oral malodor after validating OLS with odoriferous sulfur compounds in mouth air among Korean adults. A total of 330 adults aged 47-86 years were recruited from the Yangpyeong health cohort, South Korea, in 2015. Oral malodor was assessed using a 6-point OLS by a trained dentist and validated with the concentrations of hydrogen sulfide (HS) and methyl mercaptan (MM) using a gas chromatographer. Periodontitis was measured by assessing the radiographic alveolar bone loss on digital orthopantomography. Statistical analyses including descriptive statistics, partial correlation, ANOVA, and multivariable logistic regression with putative confounders were applied. OLS was significantly correlated with the concentrations of HS and MM (partial r = 0.401 and 0.392, respectively; both p<0.001) after controlling for confounders. Individuals with periodontitis had 1.8 times the risk of OLS-defined oral malodor in multivariable models (adjusted odds ratio = 1.77 in the model with the number of teeth and 1.82 in the model with denture wearing; p = 0.047 and 0.035, respectively). Periodontitis was associated with OLS-defined oral malodor among Korean adults independent of known confounders. Periodontal conditions should be considered for clinical practice and research of oral malodor.

PMID:33661974 | DOI:10.1371/journal.pone.0247947

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Nevin Manimala Statistics

Clinical and microbiological characterization of sepsis and evaluation of sepsis scores

PLoS One. 2021 Mar 4;16(3):e0247646. doi: 10.1371/journal.pone.0247646. eCollection 2021.

ABSTRACT

BACKGROUND: Despite the necessity of early recognition for an optimal outcome, sepsis often remains unrecognized. Available tools for early recognition are rarely evaluated in low- and middle-income countries. In this study, we analyzed the spectrum, treatment and outcome of sepsis at an Ethiopian tertiary hospital and evaluated recommended sepsis scores.

METHODS: Patients with an infection and ≥2 SIRS criteria were screened for sepsis by SOFA scoring. From septic patients, socioeconomic and clinical data as well as blood cultures were collected and they were followed until discharge or death; 28-day mortality was determined.

RESULTS: In 170 patients with sepsis, the overall mortality rate was 29.4%. The recognition rate by treating physicians after initial clinical assessment was low (12.4%). Increased risk of mortality was significantly associated with level of SOFA and qSOFA score, Gram-negative bacteremia (in comparison to Gram-positive bacteremia; 42.9 versus 16.7%), and antimicrobial regimen including ceftriaxone (35.7% versus 19.2%) or metronidazole (43.8% versus 25.0%), but not with an increased respiratory rate (≥22/min) or decreased systolic blood pressure (≤100mmHg). In Gram-negative isolates, extended antimicrobial resistance with expression of extended-spectrum beta-lactamase and carbapenemase genes was common. Among adult patients, sensitivity and specificity of qSOFA score for detection of sepsis were 54.3% and 66.7%, respectively.

CONCLUSION: Sepsis is commonly unrecognized and associated with high mortality, showing the need for reliable and easy-applicable tools to support early recognition. The established sepsis scores were either of limited applicability (SOFA) or, as in the case of qSOFA, were significantly impaired in their sensitivity and specificity, demonstrating the need for further evaluation and adaptation to local settings. Regional factors like malaria endemicity and HIV prevalence might influence the performance of different scores. Ineffective empirical treatment due to antimicrobial resistance is common and associated with mortality. Local antimicrobial resistance statistics are needed for guidance of calculated antimicrobial therapy to support reduction of sepsis mortality.

PMID:33661970 | DOI:10.1371/journal.pone.0247646

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Nevin Manimala Statistics

Learning temporal attention in dynamic graphs with bilinear interactions

PLoS One. 2021 Mar 4;16(3):e0247936. doi: 10.1371/journal.pone.0247936. eCollection 2021.

ABSTRACT

Reasoning about graphs evolving over time is a challenging concept in many domains, such as bioinformatics, physics, and social networks. We consider a common case in which edges can be short term interactions (e.g., messaging) or long term structural connections (e.g., friendship). In practice, long term edges are often specified by humans. Human-specified edges can be both expensive to produce and suboptimal for the downstream task. To alleviate these issues, we propose a model based on temporal point processes and variational autoencoders that learns to infer temporal attention between nodes by observing node communication. As temporal attention drives between-node feature propagation, using the dynamics of node interactions to learn this key component provides more flexibility while simultaneously avoiding issues associated with human-specified edges. We also propose a bilinear transformation layer for pairs of node features instead of concatenation, typically used in prior work, and demonstrate its superior performance in all cases. In experiments on two datasets in the dynamic link prediction task, our model often outperforms the baseline model that requires a human-specified graph. Moreover, our learned attention is semantically interpretable and infers connections similar to actual graphs.

PMID:33661968 | DOI:10.1371/journal.pone.0247936

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Nevin Manimala Statistics

Improving the replicability of neuroimaging findings by thresholding effect sizes instead of p-values

Hum Brain Mapp. 2021 Mar 4. doi: 10.1002/hbm.25374. Online ahead of print.

ABSTRACT

The classical approach for testing statistical images using spatial extent inference (SEI) thresholds the statistical image based on the p-value. This approach has an unfortunate consequence on the replicability of neuroimaging findings because the targeted brain regions are affected by the sample size-larger studies have more power to detect smaller effects. Here, we use simulations based on the preprocessed Autism Brain Imaging Data Exchange (ABIDE) to show that thresholding statistical images by effect sizes has more consistent estimates of activated regions across studies than thresholding by p-values. Using a constant effect size threshold means that the p-value threshold naturally scales with the sample size to ensure that the target set is similar across repetitions of the study that use different sample sizes. As a consequence of thresholding by the effect size, the type 1 and type 2 error rates go to zero as the sample size gets larger. We use a newly proposed robust effect size index that is defined for an arbitrary statistical image so that effect size thresholding can be used regardless of the test statistic or model.

PMID:33660923 | DOI:10.1002/hbm.25374

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Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers

Clin Transl Sci. 2021 Mar 4. doi: 10.1111/cts.12989. Online ahead of print.

ABSTRACT

Trandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single-dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (Cmax ) and area under the curve from 0 to 72 h (AUC0-72 h ) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.

PMID:33660934 | DOI:10.1111/cts.12989

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Novel biomarkers associated with incident heart failure in 10 106 Finnish men

ESC Heart Fail. 2021 Feb;8(1):605-614. doi: 10.1002/ehf2.13132. Epub 2020 Dec 5.

ABSTRACT

AIMS: There are only a few studies on novel biomarkers for incident heart failure (HF). We investigated the association of multiple circulating biomarkers with incident HF in a large prospective population-based study.

METHODS AND RESULTS: Conventional risk factors and inflammatory biomarkers were measured, and systemic metabolic measures determined by a high-throughput serum nuclear magnetic resonance platform in a population-based Metabolic Syndrome in Men study including 10 106 Finnish men without HF at baseline. During an 8.8 year follow-up, 172 (1.7%) participants developed HF. Adiponectin, high-sensitivity C-reactive protein (hs-CRP), glycoprotein acetyls, alanine, phenylalanine, glycerol, and pyruvate were associated with incident HF in unadjusted Cox regression analyses, in addition to age, systolic blood pressure, body mass index (BMI), waist circumference, fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), and urinary albumin excretion rate (UAER). After adjustment for age, BMI, diabetes, and statin medication, only adiponectin [hazard ratio (HR) 1.18 (1.10-1.26, P = 4.1E-08)], pyruvate [HR 1.38 (1.28-1.50, P = 8.2E-05)], and UAER [HR 1.15 (1.11-1.18, P = 7.8E-06)] remained statistically significant. In principal component analysis of biomarkers associated with HF in univariate Cox regression analysis, we identified six components, explaining 61.7% of total variance. Four principal components, one with significant loadings on waist, BMI, fasting plasma insulin, interleukin 1 receptor antagonist, and hs-CRP; another on pyruvate, glycoprotein acetyls, alanine, glycerol and HbA1c; third on age and glomerular filtration rate; and fourth on systolic blood pressure, UAER, and adiponectin, significantly associated with incident HF.

CONCLUSIONS: Several novel metabolic and inflammatory biomarkers were associated with incident HF, suggesting early activation of respective pathways in the pathogenesis of HF.

PMID:33660951 | DOI:10.1002/ehf2.13132