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Population Risk Factors for Nulliparous, Term, Singleton, Vertex Cesarean Birth: A National Cross-sectional Study

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

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Evaluation of e-OSPE as compared to traditional OSPE: A pilot study

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

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The relationship between vitamin D levels and cognitive impairment in patients with multiple sclerosis

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):2021-2030. doi: 10.26355/eurrev_202102_25105.

ABSTRACT

OBJECTIVE: Neurocognitive impairment is one of the most common manifestations of multiple sclerosis (MS). However, the pathophysiology of this issue is still poorly understood. The objective of this study is to investigate the relationship between vitamin D levels and cognitive function in patients with MS as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB).

PATIENTS AND METHODS: This was a cross-sectional, case-control study; the subjects were 39 Saudi patients diagnosed with MS. For all participants, demographic information, including age, sex, and educational level, was collected. Participants were also evaluated using the disease steps scale and the PHQ-9 scale. Their vitamin D levels were assessed, and the participants completed a computerized cognitive assessment using the CANTAB.

RESULTS: From the total sample of 39 patients with MS, 31 (79.5%) were female. Physical disability due to MS was insignificant in 25 (64.1%) of the subjects and significant in 14 (35.9%). Seventeen (43.6%) of the participants had normal vitamin D levels; 22 (56.4%) had low vitamin D levels. The MS patients had lower MOT mean errors than the control group, and this difference was statistically significant (t = -4.313, p < 0.01). Moreover, the scores of the two groups for all subcategories of the memory domain were different at statistically significant levels. Furthermore, the control group had higher PAL total errors (adjusted), PAL total errors (6 shapes, adjusted), and PRM percent correct than the MS patients (p < 0.01). The control group also achieved lower scores on SWM between errors and SWM strategy than the MS patients (p < 0.01). The MOT mean error was found to correlate with the disease steps score (r = 0.394, p < 0.05) and with significant physical disability (r = 0.457, p< 0.01). In the memory domain, PAL total errors (adjusted) correlated with age (r = 0.381, p < 0.05), SWM between errors correlated with age at onset of disease (r = 0.345, p < 0.05), and vitamin D level (r = 0.335, p < 0.05) and SWM strategy correlated with the number of relapses in the past 12 months (r = -0.355, p < 0.05).

CONCLUSIONS: Cognitive performance was impaired in patients with MS. Vitamin D deficiency, a potentially modifiable risk factor, independently predicted cognitive impairment in MS patients.

PMID:33660814 | DOI:10.26355/eurrev_202102_25105

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Omega-3 fatty acids supplementation on major cardiovascular outcomes: an umbrella review of meta-analyses of observational studies and randomized controlled trials

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):2079-2092. doi: 10.26355/eurrev_202102_25113.

ABSTRACT

OBJECTIVE: Omega-3 fatty acids are commonly used as a lipid-lowering agent or dietary supplement for the purpose of prevention of cardiovascular diseases. However, even large-scale clinical trials have not shown significant results demonstrating clear clinical benefits in cardiovascular diseases. Thus, this umbrella review aims to summarize and evaluate the evidence of clinical effects of omega-3 fatty acids supplementation on cardiovascular outcomes through comprehensive analyses of previous randomized controlled trials (RCTs) or observational cohort studies.

MATERIALS AND METHODS: We conducted relevant publication search in PubMed, Embase, and Cochrane Database of Systematic Reviews. We retrieved and analyzed 3,298 articles published until August 28th, 2019.

RESULTS: We identified 29 relevant articles and analyzed 83 meta-analyses of RCTs or cohort studies therefrom. As a result, we identified 12 cardiovascular outcomes that are related to omega-3 fatty acids supplementation. Among them, total mortality from major cardiovascular causes (RR 0.92, 95% CI 0.86 to 0.98) had significant inverse associations, and moreover, statistical significances were maintained even in subgroup analysis of large-scale RCTs including more than 1,000 patients (RR 0.94, 95% CI 0.88 to 0.99).

CONCLUSIONS: Our umbrella review study shows that omega-3 fatty acids supplementation have a clinical benefit in reducing mortality from cardiovascular causes. However, many studies still have shown conflicting results, and therefore, further studies will be needed to verify the clinical benefit of omega-3 supplementation.

PMID:33660821 | DOI:10.26355/eurrev_202102_25113

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A pilot study of the effect of rivaroxaban in sickle cell anemia

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

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Thymoquinone improves testicular damage and sperm quality in experimentally varicocele-induced adolescent rats

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

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iLearnPlus: a comprehensive and automated machine-learning platform for nucleic acid and protein sequence analysis, prediction and visualization

Nucleic Acids Res. 2021 Feb 28:gkab122. doi: 10.1093/nar/gkab122. Online ahead of print.

ABSTRACT

Sequence-based analysis and prediction are fundamental bioinformatic tasks that facilitate understanding of the sequence(-structure)-function paradigm for DNAs, RNAs and proteins. Rapid accumulation of sequences requires equally pervasive development of new predictive models, which depends on the availability of effective tools that support these efforts. We introduce iLearnPlus, the first machine-learning platform with graphical- and web-based interfaces for the construction of machine-learning pipelines for analysis and predictions using nucleic acid and protein sequences. iLearnPlus provides a comprehensive set of algorithms and automates sequence-based feature extraction and analysis, construction and deployment of models, assessment of predictive performance, statistical analysis, and data visualization; all without programming. iLearnPlus includes a wide range of feature sets which encode information from the input sequences and over twenty machine-learning algorithms that cover several deep-learning approaches, outnumbering the current solutions by a wide margin. Our solution caters to experienced bioinformaticians, given the broad range of options, and biologists with no programming background, given the point-and-click interface and easy-to-follow design process. We showcase iLearnPlus with two case studies concerning prediction of long noncoding RNAs (lncRNAs) from RNA transcripts and prediction of crotonylation sites in protein chains. iLearnPlus is an open-source platform available at https://github.com/Superzchen/iLearnPlus/ with the webserver at http://ilearnplus.erc.monash.edu/.

PMID:33660783 | DOI:10.1093/nar/gkab122

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Restricted mean survival time in advanced non-small cell lung cancer treated with immune checkpoint inhibitors

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1881-1889. doi: 10.26355/eurrev_202102_25083.

ABSTRACT

OBJECTIVE: The purpose of this study was to review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma with wild-type epidermal grow factor receptor (EGFR) or anaplastic lymphoma kinase.

MATERIALS AND METHODS: After a standard literature search, we identified all randomized studies published on this issue. Our first inclusion criterion was the use of pembrolizumab, nivolumab, atezolizumab or durvalumab in the treatment arm versus chemotherapy in the control arm. The second criterion was the availability of information on overall survival at 2 years. The restricted mean survival time (RMST) was used to analyze the survival curves and rank the treatments.

RESULTS: From the eligible studies, we selected 5 randomized trials that met our inclusion criteria. These trials studied a total of 11 cohorts of patients in whom the treatment arm received ICI as monotherapy (n=3) or in combination with either chemotherapy (n=2) or other monoclonal antibodies (n=1). All the control groups (n=5) received chemotherapy. Pembrolizumab (alone or in combination) showed improvement in overall survival compared with controls, but with borderline statistical significance. Nivolumab, atezolizumab and durvalumab failed to demonstrate any survival advantage. Overall, the RMSTs provided more conservative results than those previously reported using the hazard ratio. In comparing the values of RMST across treatments, pembrolizumab combined with chemotherapy ranked first.

CONCLUSIONS: Our results summarized the efficacy of these treatments and showed that only pembrolizumab can have a role as the first-line treatment of NSCLC. These findings are at variance with those previously reported using the hazard ratio as the outcome measure.

PMID:33660798 | DOI:10.26355/eurrev_202102_25083

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Differential diagnosis between acinic cell carcinoma and pleomorphic adenoma using the quantitative parameters of contrast-enhanced ultrasound

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1936-1943. doi: 10.26355/eurrev_202102_25093.

ABSTRACT

OBJECTIVE: To investigate the value of differential diagnosis between acinic cell carcinoma (ACC) and pleomorphic adenoma (PA) using the quantitative parameters of contrast-enhanced ultrasound (CEUS).

PATIENTS AND METHODS: Twenty-two ACC and 98 PA were retrospectively analyzed. These patients had been examined via routine pre-surgical two-dimensional ultrasound and CEUS. The examination results were confirmed by biopsy pathology. Qontrast 4.0 imaging analysis software was applied to obtain the maximum intensity (PEAK), time to peak (TTP), regional blood volume (RBV), regional blood flow (RBF), maximum signal intensity (SImax) and mean signal intensity (SImean) through quantitative analysis. The differences between ACC and PA were compared regarding the conventional ultrasound images and the quantitative parameters of CEUS. ROC curves were drawn to evaluate the diagnostic value of these parameters.

RESULTS: There were no statistically significant differences between salivary gland ACC and PA in the manifestations of conventional two-dimensional ultrasound examination regarding morphology, internal echo and the boundary (p > 0.05). However, there were significant differences in PEAK, RBV, RBF, SImax and SImean between ACC and PA (p < 0.05). Additionally, the five quantitative parameters of CEUS were all highly accurate diagnostic indicators. The maximum area under the curve of each parameter was 0.888, sensitivity 72.6%, specificity 90.9% and accuracy 81.8%.

CONCLUSIONS: The quantitative parameters of CEUS are helpful for differentially diagnosing salivary ACC and PA.

PMID:33660803 | DOI:10.26355/eurrev_202102_25093

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The association of serum Kallikrein-8 with cognitive function in vascular dementia

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1997-2002. doi: 10.26355/eurrev_202102_25101.

ABSTRACT

OBJECTIVE: Kallikrein-8 (KLK8) is a secreted serine protease related to learning and memory. Evidence has confirmed the important role of KLK8 in neuroplasticity. However, the role of KLK8 in vascular dementia (VaD) is unclear.

PATIENTS AND METHODS: The study recruited 88 VaD patients and 72 normal controls. All subjects were tested for cognitive function by Mini-Mental State Examination (MMSE) upon admission, and their demographic and biochemical data were collected. A sandwich Enzyme-Linked Immunosorbent Assay (ELISA) test was used to detect serum KLK8 levels. The demographic and biochemical data of the two groups of subjects were compared. Spearman’s correlation and multivariate regression analysis were used to determine whether serum KLK8 in VaD patients is a risk factor for cognitive function.

RESULTS: A total of 88 VaD patients and 72 controls with normal cognitive function were recruited and divided into VaD group and control group. Except for TT3 (p=0.002), there was no statistically significant difference in other demographic and biochemical data between the two groups (p>0.05). The results of ELISA indicated that the serum KLK8 in VaD patients was significantly higher than that of the control population (p<0.001). Spearman correlation analysis indicated that the serum KLK8 in VaD was significantly inversely correlated with the MMSE score. The results of Spearman’s correlation analysis showed that the serum KLK8 level of VaD was significantly inversely correlated with the MMSE (r=-0.305, p=0.017). After correcting for interference factors, the correlation between the two is still significant (β=0.398, p=0.024).

CONCLUSIONS: Serum KLK8 may be an independent risk factor affecting the cognitive function of VaD, which is worthy of further research.

PMID:33660811 | DOI:10.26355/eurrev_202102_25101