Nevin Manimala

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):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

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

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

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

Biochem Mol Biol Educ. 2021 Mar 4. doi: 10.1002/bmb.21500. Online ahead of print.

ABSTRACT

Objectively Structured Clinical/Practical Examination (OSCE/OSPE) has been the backbone of the assessment system of graduate medical education for over three decades. We have developed an electronic Objectively Structured Practical Examination (e-OSPE) in Medical Biochemistry using the freely available Google forms to mitigate the academic disruption posed by COVID-19 pandemic in our resource-poor setting. Ten e-OSPE stations created, interlinked, and time-restricted. Fifty undergraduate students appeared for the e-OSPE examination on a prefixed date and time. Learner feedback was collected immediately after the completion of the examination. Facilitator feedback was also collected. Students’ mean scores in e-OSPE and traditional OSPE were 78.15% and 74.56%, respectively. Their difference was not statistically significant (paired t-test two-tailed p-value 0.0979). Thus, the results of e-OSPE are reliable as compared to traditional OSPE. Bland Altman Plot revealed 92% of students had scores that were in the agreeable limit of both traditional OSPE and e-OSPE. Both the learners and facilitators were in consensus that the online format of e-OSPE is a good alternative for assessment (0.67 and 0.82); their experience was good (0.72 and 0.92) and conduction was well organized (0.73 and 0.86). Several suggestions were also received to make e-OSPE even more effective. In conclusion, this pilot study showed e-OSPE can be an effective alternative to traditional OSPE when “in-person” evaluation is not possible such as in the current era of COVID-19 even in resource-limited settings.

PMID:33660917 | DOI:10.1002/bmb.21500

BJOG. 2021 Mar 4. doi: 10.1111/1471-0528.16684. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize medical, obstetric, and demographic risk factors associated with nulliparous, term, singleton, vertex (NTSV) cesarean birth.

STUDY DESIGN: Cross sectional study.

SETTING: United States delivery hospitalizations.

POPULATION: NTSV births in 2016-2018 US natality data.

METHODS: This study analyzed a national sample of natality data generated by the United States National Vital Statistics System. NTSV deliveries were identified. The primary outcome was cesarean birth. Risk factors including maternal age, body mass index (BMI), and pre-gestational diabetes were analyzed. Multivariable log-linear regression models analyzed factors associated with NTSV cesarean with adjusted risk ratios (aRR) as measures of effect.

RESULTS: Of 3,764,707 of 11,622,400 deliveries that met NTSV criteria the cesarean rate was 25.9%. Maternal age 35-39 (aRR 1.51, 95% CI 1.50-1.52) and 40-54 (aRR 2.03, 95% 2.00-2.05) compared to age 19-34, BMI 25 to <30 kg/m² (aRR 1.32, 95% CI 1.31-1.33), 30 to <35 kg/m² (aRR 1.57 95% CI 1.56-1.58), 35 to <40 kg/m² (aRR 1.82, 95% CI 1.80-1.83), and ≥40 kg/m² (aRR 2.17, 95% CI 2.15-2.19) compared to 18.5-24.9 kg/m² , and pre-gestational diabetes (aRR 1.54, 95% CI 1.51-1.57) were all associated with increased risk. Risk factors allowed stratification of patients into high versus low risk groups. The NTSV cesarean rate was 37.9% in women who had ≥1 of the following characteristics: age ≥35 years, BMI ≥30 kg/m² , or pregestational diabetes. In comparison, the NTSV cesarean rate was 20.8% among of women without any of these three risk factors (p<0.01) CONCLUSION: Among NTSV births, BMI, maternal age, and medical conditions are important risk factors for cesarean.

PMID:33660911 | DOI:10.1111/1471-0528.16684

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

Andrologia. 2021 Mar 4:e14033. doi: 10.1111/and.14033. Online ahead of print.

ABSTRACT

The aim of this study was to investigate the protective and therapeutic effects of thymoquinone against the negative effects of varicocele on testicular tissue and sperm morphology. Five groups were formed by random selection from a total of 40 adult male Wistar rats (n = 8). Thymoquinone (5 mg/kg/day) was administered intraperitoneally to the varicocele-dimethyl sulfoxide-olive oil-thymoquinone (VT) group and the sham-thymoquinone group. At the end of the 60th day, all groups were anaesthetised and the left testis was removed from the body quickly. One half of the testis tissue, which was divided into two, was separated for biochemical and Western blot analysis, while the other half were fixed in Bouin’s fixative. As a result of biochemical, molecular and histopathological analyses, a statistically significant increase was found in the varicocele group testicular tissues in the malondialdehyde level, apoptotic index, Bax expression, cytochrome c expression and Bax/Bcl-2 ratio compared with the sham group. In addition, histopathological changes characterised by partial or complete degeneration of the germinal epithelium were observed in the seminiferous tubules in the same group. Total oxidant status level and sperm count with abnormal morphology increased in varicocele group, whereas total antioxidant status level decreased. In the VT group, all of the biochemical, molecular and histopathological changes detected in the varicocele group were statistically significantly reduced. When the findings obtained in this study are evaluated, it can be said that thymoquinone has the potential to be used as a preventive and therapeutic pharmacological agent in the medical treatment of varicocele. Although the exact mechanism of action of thymoquinone has not been fully elucidated, the findings obtained in this study support the view that thymoquinone showed a cytoprotective effect by reducing apoptosis, oxidative stress and lipid peroxidation.

PMID:33660882 | DOI:10.1111/and.14033

Transfusion. 2021 Mar 4. doi: 10.1111/trf.16343. Online ahead of print.

ABSTRACT

INTRODUCTION: The contribution of coagulation activation to the pathogenesis of sickle cell disease (SCD) remains incompletely defined. We evaluated the efficacy and safety of rivaroxaban, an oral direct factor Xa inhibitor, in subjects with sickle cell anemia.

MATERIALS AND METHODS: In this pilot, single-center, randomized, double-blind, placebo-controlled, crossover study, eligible subjects with sickle cell anemia received rivaroxaban or placebo. The effect of rivaroxaban on coagulation activation, endothelial activation, inflammation, and microvascular blood flow was evaluated.

RESULTS: Fourteen patients (HbSS – 14; females – 9) with mean age of 38 ± 10.6 years were randomized to receive rivaroxaban 20 mg daily or placebo for 4 weeks and, following a 2-week washout phase, were “crossed-over” to the treatment arm opposite to which they were initially assigned. Mean adherence to treatment with rivaroxaban, assessed by pill counts, was 85.6% in the first treatment period and 93.6% in the second period. Treatment with rivaroxaban resulted in a decrease from baseline of thrombin-antithrombin complex versus placebo (-34.4 ug/L [95% CI: -69.4, 0.53] vs. 0.35 ug/L [95% CI: -3.8, 4.5], p = .08), but the difference was not statistically significant. No significant differences were observed in changes from baseline of D-dimer, inflammatory, and endothelial activation markers or measures of microvascular blood flow. Rivaroxaban was well tolerated.

CONCLUSIONS: Rivaroxaban was safe but did not significantly decrease coagulation activation, endothelial activation, or inflammation. Rivaroxaban did not improve microvascular blood flow. Adequately powered studies are required to further evaluate the efficacy of rivaroxaban in SCD. Clinicaltrials.gov Identifier: NCT02072668.

PMID:33660875 | DOI:10.1111/trf.16343