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Nevin Manimala Statistics

Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics

Biol Chem. 2021 Jan 20;402(6):749-757. doi: 10.1515/hsz-2020-0331. Print 2021 May 26.

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

PMID:33951765 | DOI:10.1515/hsz-2020-0331

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Nevin Manimala Statistics

Psychopathologic Profiles and Clusters in Tertiary Clinic Referred Patients with Adult Attention Deficit Hyperactivity Disorder: A Person-Centered Analysis

Psychiatry Investig. 2021 Apr;18(4):304-311. doi: 10.30773/pi.2020.0331. Epub 2021 Apr 25.

ABSTRACT

OBJECTIVE: Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach.

METHODS: In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis.

RESULTS: Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1.

CONCLUSION: Further studies are needed to confirm the relationships observed in the present study.

PMID:33951777 | DOI:10.30773/pi.2020.0331

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Nevin Manimala Statistics

R and nlmixr as a gateway between statistics and pharmacometrics

CPT Pharmacometrics Syst Pharmacol. 2021 Apr;10(4):283-285. doi: 10.1002/psp4.12618.

NO ABSTRACT

PMID:33951757 | DOI:10.1002/psp4.12618

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Nevin Manimala Statistics

The effect of Chlorella vulgaris on obesity related metabolic disorders: a systematic review of randomized controlled trials

J Complement Integr Med. 2021 May 5. doi: 10.1515/jcim-2021-0024. Online ahead of print.

ABSTRACT

OBJECTIVES: Chlorella vulgaris (CV) as a unicellular algae is a dietary supplement with beneficial nutritious content, used for decades in some countries. Positive effects for CV supplementation on metabolic parameters has been established in animal and human studies. However there is a gap for this results summary for a definite conclusion announce. This systematic review aimed to summarize the effects of CV on body weight, lipid profile, and blood glucose.

CONTENT: PRISMA guidelines were charted in this review. Subject search was performed in MEDLINE, ProQuest, PubMed, ISI web of sciences, Google scholar, Cochrane and Scopus databases for randomized clinical trials published in English languages, until December 2020, which assessed the effects of CV on metabolic syndrome related symptoms in clinical trials.

SUMMARY: Out of 4,821 records screened, after duplicate and irrelevant exclusion by title and abstract, 20 articles remained for full text screening. Finally a total of 12 articles met the study inclusion criteria and were assessed for study method and results.

OUTLOOK: The findings showed controversies in anthropometric, glycemic and lipid profile effects. CV may have beneficial effects on obesity-related metabolic disorders; however, collected studies lacked statistical power to reach a definite conclusion. More well-designed studies are required.

PROSPERO REGISTRATION NUMBER: CRD42019123683.

PMID:33951762 | DOI:10.1515/jcim-2021-0024

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Nevin Manimala Statistics

Antipsychotics are related to psychometric conversion to psychosis in ultra-high-risk youth

Early Interv Psychiatry. 2021 May 5. doi: 10.1111/eip.13158. Online ahead of print.

ABSTRACT

BACKGROUND: The prescription of antipsychotics outside overt psychotic conditions remains controversial, especially in youth where it is relatively widespread. Furthermore, some studies seem to indicate that antipsychotic exposure in individuals at ultra-high-risk (UHR) for psychosis is associated with higher conversion rates. This study was set up to test whether the inter-current prescription of antipsychotics in UHR patients was related to the psychometric threshold for a diagnosis of psychosis.

METHODS: The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 125 UHR participants. Standard psychometric criteria were used to quantify conversion to psychosis. Kaplan-Mayer and Cox proportional hazard survival analysis were applied to determine the impact of having or not received the prescription of an antipsychotic drug.

RESULTS: Over the study period 30 (24%) subjects received the prescription of an antipsychotic. In the sample, there were 31 participants (25%) who had reached the psychometric threshold for conversion to psychosis after 2 years of treatment. UHR people who received a prescription of antipsychotics during the first 2 years of treatment were statistically more likely to reach the psychometric threshold for conversion to psychosis on the BPRS: Hazard ratio = 3.03 (95%CI: 1.49-6.16); p = .003.

CONCLUSION: This finding supports the hypothesis that the prescription of antipsychotics within UHR cohorts is to be considered a red flag for higher incipient risk of conversion to psychosis.

PMID:33951751 | DOI:10.1111/eip.13158

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Nevin Manimala Statistics

Impact of study design and statistical model in pharmacogenetic studies with gene-treatment interaction

CPT Pharmacometrics Syst Pharmacol. 2021 Apr;10(4):340-349. doi: 10.1002/psp4.12624.

ABSTRACT

Gene-treatment interactions, just like drug-drug interactions, can have dramatic effects on a patient response and therefore influence the clinician decision at the patient’s bedside. Crossover designs, although they are known to decrease the number of subjects in drug-interaction studies, are seldom used in pharmacogenetic studies. We propose to evaluate, via realistic clinical trial simulations, to what extent crossover designs can help quantifying the gene-treatment interaction effect. We explored different scenarios of crossover and parallel design studies comparing two symptom-modifying treatments in a chronic and stable disease accounting for the impact of a one gene and one gene-treatment interaction. We varied the number of subjects, the between and within subject variabilities, the gene polymorphism frequency and the effect sizes of the treatment, gene, and gene-treatment interaction. Each simulated dataset was analyzed using three models: (i) estimating only the treatment effect, (ii) estimating the treatment and the gene effects, and (iii) estimating the treatment, the gene, and the gene-treatment interaction effects. We showed how ignoring the gene-treatment interaction results in the wrong treatment effect estimates. We also highlighted how crossover studies are more powerful to detect a treatment effect in the presence of a gene-treatment interaction and more often lead to correct treatment attribution.

PMID:33951752 | DOI:10.1002/psp4.12624

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Nevin Manimala Statistics

Welcome to the statistics and pharmacometrics themed issue

CPT Pharmacometrics Syst Pharmacol. 2021 Apr;10(4):273-274. doi: 10.1002/psp4.12625.

NO ABSTRACT

PMID:33951754 | DOI:10.1002/psp4.12625

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Nevin Manimala Statistics

Preoperative Parameters to Predict the Development of Symptomatic Lymphoceles after Radical Prostatectomy

Urol Int. 2021 May 5:1-8. doi: 10.1159/000514041. Online ahead of print.

ABSTRACT

INTRODUCTION: Symptomatic lymphoceles (SLs) represent the most common complication after radical prostatectomy (RP) and pelvic lymph node dissection (PLND). To date, preoperative risk factors are missing.

METHODS: Clinical and pathological data of 592 patients who underwent RP and PLND were evaluated. Included parameters were age, BMI, prostate-specific antigen (PSA), PSA ratio, PSA density, number of resected and/or positive lymph nodes, previous abdominal surgery/pelvic radiotherapy, anticoagulation, and surgical approach.

RESULTS: Fifty-nine patients (10%) developed an SL, of which 57 underwent open retropubic radical prostatectomy (RRP) and 2 underwent robot-assisted radical prostatectomy (RARP). Multivariate logistic regression revealed the following parameters as statistically significant risk factors: PSA (odds ratio [OR] = 2.23; 95% CI [1.25; 5.04], p = 0.04), number of resected lymph nodes (OR = 1.47; 95% CI [1.10; 1.97], p < 0.01), previous abdominal surgery (OR = 2.58; 95% CI [1.38; 4.91], p < 0.01), and surgical approach (OR = 0.08; 95% CI [0.01; 0.27], p < 0.01). Previous oral anticoagulation showed almost statistically significant results (OR = 2.39 [0.92; 5.51], p = 0.05).

CONCLUSION: The risk for SL might be predictable considering preoperative risk factors such as PSA, previous abdominal surgery and anticoagulation. To avoid SL, RARP should be the procedure of choice. If RRP is considered, patients at risk for SL may benefit from peritoneal fenestration during RP.

PMID:33951669 | DOI:10.1159/000514041

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Nevin Manimala Statistics

Maternal Serum Placental Protein-13 Levels in the Prediction of Pregnancies with Abnormal Invasive Placentation

Z Geburtshilfe Neonatol. 2021 May 5. doi: 10.1055/a-1475-5413. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether placental protein-13 (PP-13) measured in the serum of pregnant women could predict abnormal invasive placentation (AIP) detected by color Doppler ultrasound (US) and magnetic resonance imaging scan in addition to the routine US scan during the third trimester.

MATERIALS AND METHODS: The prospective case-control study included patients subdivided in 2 groups: 42 pregnant women with a singleton pregnancy at 28-32 weeks of gestation with only suspected AIP, and 32 healthy pregnant women. The serum PP-13 levels were measured in both groups using an enzyme-linked immunosorbent assay (ELISA) method and statistically compared. The cases of AIP were confirmed by placental histopathological examination and/or the uterus removed by hysterectomy after elective caesarean section.

RESULTS: Serum PP-13 levels of pregnant women with AIP were significantly higher (p<0.001) than those of controls (650.32±387.33 vs. 231.43±94.33). Statistical analysis of maternal serum PP-13 levels above the threshold of 312 pg/ml (measured in the early third trimester) predicted AIP with 76.2% sensitivity and 75% specificity.

CONCLUSION: Maternal serum PP-13 may have a role in the pathophysiology of AIP owing to its high serum value in the AIP group. The maternal serum dosage of PP-13 levels could improve pregnancy management in those patients suspected of having AIP.

PMID:33951735 | DOI:10.1055/a-1475-5413

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Nevin Manimala Statistics

Predicting risk of erectile dysfunction in patients with nonalcoholic fatty liver disease

Andrologia. 2021 May 5:e14091. doi: 10.1111/and.14091. Online ahead of print.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is one of the risk factors for erectile dysfunction (ED). We aimed to predict the risk of ED in patients with NAFLD. The study included 146 male patients complaining impotence admitted to the urology outpatient clinic aged 24-80 years without a history of alcohol use who underwent abdominal ultrasonography between February 2018 and January 2019. 106 patients with NAFLD and 40 men without NAFLD were included in the study. Clinical and laboratory parameters, ED status according to International Index of Erectile Function-5 were compared between patients with and without NAFLD. The mean age of patients was 51.47 ± 10.34 years. NAFLD was detected in 72.6% of the patients. No statistically significant difference was found regarding mean age, BMI, IIEF-5 scores, DM status, serum glucose levels (p > .05). Fasting insulin levels, hypertension (HT), insulin resistance (IR) and ED status of the patients with NAFLD were significantly higher than patients without NAFLD (p < .05). NAFLD was found to be a significantly independent associated with ED. We also found that patients with NAFLD have risk of ED 2.92 times higher than without NAFLD (OR: 2.92). For the patients presenting with erectile dysfunction, hepatic steatosis should also be considered.

PMID:33951744 | DOI:10.1111/and.14091