Category: Nevin Manimala

Postgrad Med J. 2024 Jan 8:qgad134. doi: 10.1093/postmj/qgad134. Online ahead of print.

ABSTRACT

PURPOSE: Bar charts of numerical data, often known as dynamite plots, are unnecessary and misleading. Their tendency to alter the perception of mean’s position through the within-the-bar bias and their lack of information on the distribution of the data are two of numerous reasons. The machine learning tool, Barzooka, can be used to rapidly screen for different graph types in journal articles.We aim to determine the proportion of original research articles using dynamite plots to visualize data, and whether there has been a change in their use over time.

METHODS: Original research articles in nine surgical fields of research were sampled based on MeSH terms and then harvested using the Python-based biblio-glutton-harvester tool. After harvesting, they were analysed using Barzooka. Over 40 000 original research articles were included in the final analysis. The results were adjusted based on previous validation data with 95% confidence bounds. Kendall τ coefficient with the Mann-Kendall test for significance was used to determine the trend of dynamite plot use over time.

RESULTS: Eight surgical fields of research showed a statistically significant decrease in use of dynamite plots over 10 years. Oral and maxillofacial surgery showed no significant trend in either direction. In 2022, use of dynamite plots, dependent on field and 95% confidence bounds, ranges from ~30% to 70%.

CONCLUSION: Our results show that the use of dynamite plots in surgical research has decreased over time; however, use remains high. More must be done to understand this phenomenon and educate surgical researchers on data visualization practices.

PMID:38190146 | DOI:10.1093/postmj/qgad134

Cell Genom. 2023 Dec 22:100469. doi: 10.1016/j.xgen.2023.100469. Online ahead of print.

ABSTRACT

Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ^∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.

PMID:38190103 | DOI:10.1016/j.xgen.2023.100469

Oper Neurosurg (Hagerstown). 2024 Jan 8. doi: 10.1227/ons.0000000000001044. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Subpial corticectomy involving complete lesion resection while preserving pial membranes and avoiding injury to adjacent normal tissues is an essential bimanual task necessary for neurosurgical trainees to master. We sought to develop an ex vivo calf brain corticectomy simulation model with continuous assessment of surgical instrument movement during the simulation. A case series study of skilled participants was performed to assess face and content validity to gain insights into the utility of this training platform, along with determining if skilled and less skilled participants had statistical differences in validity assessment.

METHODS: An ex vivo calf brain simulation model was developed in which trainees performed a subpial corticectomy of three defined areas. A case series study assessed face and content validity of the model using 7-point Likert scale questionnaires.

RESULTS: Twelve skilled and 11 less skilled participants were included in this investigation. Overall median scores of 6.0 (range 4.0-6.0) for face validity and 6.0 (range 3.5-7.0) for content validity were determined on the 7-point Likert scale, with no statistical differences between skilled and less skilled groups identified.

CONCLUSION: A novel ex vivo calf brain simulator was developed to replicate the subpial resection procedure and demonstrated face and content validity.

PMID:38190098 | DOI:10.1227/ons.0000000000001044

High Blood Press Cardiovasc Prev. 2024 Jan 8. doi: 10.1007/s40292-023-00616-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Safety studies of anticoagulant therapy have so far been conducted on many subjects in controlled conditions (i.e., clinically monitored) and demonstrated the noninferiority of new ones over old anticoagulant drugs. Data on the propositions for the presence of symptoms and signs of bleeding among various anticoagulants in the emergency department indicate that these data do not match the data published so far.

AIM: The aim of the study was to investigate the differences in the frequency of bleeding and bleeding-related symptoms as a reason for emergency department attendance in patients on anticoagulant therapy.

METHODS: The study included patients from the emergency department of University Hospital for one year, who were on anticoagulant therapy and who met the inclusion criteria. Out of a total of 595 patients, 409 were on warfarin (68.74%), and the rest were taking direct oral anticoagulants (DOAC): dabigatran 71 (11.93%), rivaroxaban 66 (11.09%) and apixaban 49 (8.23%).

RESULTS: Out of 409 patients taking warfarin, 34.4% were adequately anticoagulated with the frequency of bleeding 13.7%, while in 57.2% of patients, PT INR was higher than the reference values with the frequency of bleeding 15.0%. A comparison between all DOAC groups and adequately anticoagulated warfarin patients in the frequency of bleeding and bleeding-related symptoms as a reason for emergency attendance yielded a difference that was marginally statistically significant (Pearson Chi-Square = 7.554, p = 0.052).

CONCLUSION: Monitoring the frequency of bleeding and bleeding-related symptoms in patients on oral anticoagulant therapy as a reason for emergency department attendance may be a new safety and efficacy factor in real-life patient scenarios.

PMID:38190093 | DOI:10.1007/s40292-023-00616-y

CNS Drugs. 2024 Jan 8. doi: 10.1007/s40263-023-01056-x. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Identifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia.

METHODS: Adults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition.

RESULTS: Of 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, Z_PANSS = -2.21, p = 0.028; Z_CGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02).

CONCLUSION: A lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China.

CLINICAL TRIALS REGISTRATION: EudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.

PMID:38190077 | DOI:10.1007/s40263-023-01056-x

J Epidemiol Glob Health. 2024 Jan 8. doi: 10.1007/s44197-023-00175-4. Online ahead of print.

ABSTRACT

Maternal and paternal age at birth is increasing globally. Maternal age may affect perinatal outcomes, but the effect of paternal age and its joint effect with maternal age are not well established. This prospective, multicenter, cohort analysis used data from the University Hospital Advanced Age Pregnant Cohort Study in China from 2016 to 2021, to investigate the separate association of paternal age and joint association of paternal and maternal age with adverse perinatal outcomes. Of 16,114 singleton deliveries, mean paternal and maternal age (± SD) was 38.0 ± 5.3 years and 36.0 ± 4.1 years. In unadjusted analyses, older paternal age was associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, preeclampsia, placenta accreta spectrum disorders, placenta previa, cesarean delivery (CD), and postpartum hemorrhage, preterm birth (PTB), large-for-gestational-age, macrosomia, and congenital anomaly, except for small-for-gestational-age. In multivariable analyses, the associations turned to null for most outcomes, and attenuated but still significant for GDM, CD, PTB, and macrosomia. As compare to paternal age of < 30 years, the risks in older paternal age groups increased by 31-45% for GDM, 17-33% for CD, 32-36% for PTB, and 28-31% for macrosomia. The predicted probabilities of GDM, placenta previa, and CD increased rapidly with paternal age up to thresholds of 36.4-40.3 years, and then plateaued or decelerated. The risks of GDM, CD, and PTB were much greater for pregnancies with younger paternal and older maternal age, despite no statistical interaction between the associations related to paternal and maternal age. Our findings support the advocation that paternal age, besides maternal age, should be considered during preconception counseling.Trial Registration NCT03220750, Registered July 18, 2017-Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03220750 .

PMID:38190051 | DOI:10.1007/s44197-023-00175-4

Biometals. 2024 Jan 8. doi: 10.1007/s10534-023-00563-0. Online ahead of print.

ABSTRACT

There is limited experimental evidence on the biochemical consequences of aluminium (Al) and cadmium (Cd) co-exposures during pregnancy and postnatal life.This study investigated the impacts of perinatal Al chloride (AlCl₃) and Cd chloride (CdCl₂) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl₃ (10 mg/kg), group 2 were administered CdCl₂ (1.5 mg/kg), while group 3 received both AlCl₃ (10 mg/kg) and CdCl₂ (1.5 mg/kg) (AlCl₃+CdCl₂), and group 4 received saline (10 mL/kg) only and served as control group. All experimental animals were chemically exposed once daily from gestation days 7-20. Upon delivery, male pups were regrouped based on maternal chemical exposure on postnatal day 21 (PND 21) and allowed to grow to adulthood until PND 78, after which they were sacrificed for assessment of neuroendocrine markers and histological investigations. There was no statistical significance (p > 0.05) on follicle stimulating hormone, testosterone, estrogen and progesterone, thyroid stimulating hormone, thyroxine (T4) in all treatment groups relative to controls|. However, AlCl₃ and AlCl₃-CdCl₂ significantly (p < 0.05) reduced triiodothyronine (T3) levels, with a profound increase in T3:T4 ratio by AlCl₃, and AlCl₃+CdCl₂ compared to control. Furthermore, pups from pregnant mice treated with CdCl₂ and AlCl₃+CdCl₂ demonstrated increased testicular malondialdehyde concentration with increased catalase activity relative to controls, suggesting oxidative imbalance. In addition, AlCl₃, CdCl₂, and AlCl₃+CdCl₂ exposures induced testicular and hypothalamic architectural disruption compared to controls, with marked architectural derangement in the AlCl₃+CdCl₂ group. Our findings suggest that prenatal co-exposures to Alcl₃ and CdCl₂ induce testicular and hypothalamic alterations in offspring via a testicular oxidative stress and thyrotoxicosis-dependent mechanisms.

PMID:38190032 | DOI:10.1007/s10534-023-00563-0

Endocrine. 2024 Jan 8. doi: 10.1007/s12020-023-03669-0. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to investigate the potential effect of Antithrombin III (ATIII) between chronic renal insufficiency and chronic coronary artery disease (chronic CAD) in type 2 diabetes mellitus (T2DM) patients.

METHODS: T2DM patients hospitalized in ZhongDa Hospital from 2013 to 2018 were enrolled. Relationships between renal function, ATIII, and chronic CAD risk were explored using multivariate regression models. Multiplicative and additive interactions were investigated between ATIII and renal function for CAD risk, and the role of ATIII was determined by bootstrap mediation analysis in patients with chronic renal dysfunction.

RESULTS: A total of 4197 patients were included in the study, with a chronic CAD prevalence of 23.02%. Low ATIII level was statistically associated with chronic renal insufficiency and elevated CAD risk even after adjustments (P < 0.05). A positive correlation between renal function and ATIII was demonstrated, and each 1 SD increase in renal function, ATIII increased by 2.947% (2.406-3.488%, P < 0.001) and 0.969% (0.297-1.642%, P < 0.001) in crude and adjusted models respectively. Patients with decreased renal function and ATIII were at the highest chronic CAD risk (OR = 1.51, 95%CI:1.15-1.98, P < 0.05), while no multiplicative and additive interaction effects were significant. Bootstrap mediation analysis estimated that ATIII mediated approximately 4.27% of the effect of chronic renal insufficiency on chronic CAD risk.

CONCLUSION: ATIII may serve as a mediator between chronic renal insufficiency and chronic CAD, providing mechanistic clues for renal-heart association and new insight into clinical therapies.

PMID:38190026 | DOI:10.1007/s12020-023-03669-0

Psychometrika. 2024 Jan 8. doi: 10.1007/s11336-023-09945-2. Online ahead of print.

ABSTRACT

Most measures of agreement are chance-corrected. They differ in three dimensions: their definition of chance agreement, their choice of disagreement function, and how they handle multiple raters. Chance agreement is usually defined in a pairwise manner, following either Cohen’s kappa or Fleiss’s kappa. The disagreement function is usually a nominal, quadratic, or absolute value function. But how to handle multiple raters is contentious, with the main contenders being Fleiss’s kappa, Conger’s kappa, and Hubert’s kappa, the variant of Fleiss’s kappa where agreement is said to occur only if every rater agrees. More generally, multi-rater agreement coefficients can be defined in a g-wise way, where the disagreement weighting function uses g raters instead of two. This paper contains two main contributions. (a) We propose using Fréchet variances to handle the case of multiple raters. The Fréchet variances are intuitive disagreement measures and turn out to generalize the nominal, quadratic, and absolute value functions to the case of more than two raters. (b) We derive the limit theory of g-wise weighted agreement coefficients, with chance agreement of the Cohen-type or Fleiss-type, for the case where every item is rated by the same number of raters. Trying out three confidence interval constructions, we end up recommending calculating confidence intervals using the arcsine transform or the Fisher transform.

PMID:38190018 | DOI:10.1007/s11336-023-09945-2

Eur J Epidemiol. 2024 Jan 8. doi: 10.1007/s10654-023-01080-7. Online ahead of print.

ABSTRACT

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site. At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (β_diab = 0.193, 95% CI 0.040; 0.346) and lower BPF (β_diab = -0.342, 95% CI -0.474; -0.210), as well as with an increased risk of dementia over 12 years of follow-up (HR_diab = 1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HR_diab = 1.12, 95% CI 1.05; 1.20, mediated part = 22.9%). This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia.

PMID:38190014 | DOI:10.1007/s10654-023-01080-7