Category: Nevin Manimala

PLoS One. 2021 Mar 4;16(3):e0247958. doi: 10.1371/journal.pone.0247958. eCollection 2021.

ABSTRACT

BACKGROUND: Recently, the use of Yttrium-90 transarterial radioembolization in non-surgical hepatocellular carcinoma was suggested but the evidence supporting its use is unclear.

METHODS: We searched Medline, Embase, Web of Science and Cochrane CENTRAL from inception up to April 14, 2020 for randomized controlled trials comparing Y90-TARE to standard of care in non-surgical HCC patients. Our primary outcome was overall survival (OS). Our secondary outcomes were progression-free survival, time to progression, disease control rate, grade ≥3 adverse events and rates of gastro-intestinal ulcers. Hazard ratios (HR) and risk ratios (RR) with random-effects model were used for our analyses. The risk of bias of the included studies was assessed using Cochrane’s RoB 2 tool.

RESULTS: Of 1,604 citations identified, eight studies (1,439 patients) were included in our analysis. No improvement in overall survival were noted when Yttrium-90 transarterial radioembolization was compared to standard treatments (HR 0.99 [95% CI 0.81-1.21], 6 studies, I2 = 77.6%). However, Yttrium-90 transarterial radioembolization was associated with fewer grade ≥3 adverse events (RR 0.64 [95% CI 0.45-0.92], 7 studies, I2 = 66%). No difference was observed on other secondary outcomes.

DISCUSSION: In non-surgical HCC patients, Yttrium-90 transarterial radioembolization was not associated with significant effect on survival, progression-free survival, time to progression, disease control rate and the incidence of gastro-intestinal ulcers but was however associated with significantly lower rates of grade ≥3 adverse events. Further randomized controlled trials are warranted to better delineate optimal treatment.

PMID:33662011 | DOI:10.1371/journal.pone.0247958

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

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

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

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

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

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

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 (C_max ) and area under the curve from 0 to 72 h (AUC_{0-72 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

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

Oral Dis. 2021 Mar 4. doi: 10.1111/odi.13815. Online ahead of print.

ABSTRACT

OBJECTIVE: The current study aimed to investigate the possible relationship between periodontal status and sexual dysfunction in perimenopausal women.

MATERIALS AND METHODS: This study was conducted on 106 participants. After the evaluation of the sexual functioning of participants with the Female Sexual Function Index (FSFI), their periodontal status and decayed-missing-filled teeth (DMFT) were assessed using appropriate indexes and obtained results were recorded for comparisons. Participants were divided into two groups by the periodontal status. Patients with periodontitis were grouped by the stage and the extent of the disease. Besides, participants were grouped according to the bleeding on probing (BOP) ratios for more detailed analyses.

RESULTS: A negative significant correlation was observed between total FSFI scores and each of the clinical periodontal parameters. Total FSFI scores and the scores of arousal, lubrication, orgasm, satisfaction, and pain domains were significantly lower in periodontitis patients (p<0.05). When the patients were grouped as having localized or generalized periodontitis or whether they had stage I, II, and III periodontitis; no statistically significant differences were observed in the distribution of general sexual dysfunction parameters across the groups (p>0.05).

CONCLUSION: Periodontal status in perimenopausal women may be associated with sexual dysfunction.

PMID:33660899 | DOI:10.1111/odi.13815