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Nevin Manimala Statistics

A network embedding approach to identify active modules in biological interaction networks

Life Sci Alliance. 2023 Jun 20;6(9):e202201550. doi: 10.26508/lsa.202201550. Print 2023 Sep.

ABSTRACT

The identification of condition-specific gene sets from transcriptomic experiments is important to reveal regulatory and signaling mechanisms associated with a given cellular response. Statistical methods of differential expression analysis, designed to assess individual gene variations, have trouble highlighting modules of small varying genes whose interaction is essential to characterize phenotypic changes. To identify these highly informative gene modules, several methods have been proposed in recent years, but they have many limitations that make them of little use to biologists. Here, we propose an efficient method for identifying these active modules that operates on a data embedding combining gene expressions and interaction data. Applications carried out on real datasets show that our method can identify new groups of genes of high interest corresponding to functions not revealed by traditional approaches. Software is available at https://github.com/claudepasquier/amine.

PMID:37339804 | DOI:10.26508/lsa.202201550

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Post Hoc Analyses of a Randomized Controlled Trial for the Effect of Pharmacist Deprescribing Intervention on the Anticholinergic Burden in Frail Community-Dwelling Older Adults

J Am Med Dir Assoc. 2023 Jun 17:S1525-8610(23)00478-4. doi: 10.1016/j.jamda.2023.05.014. Online ahead of print.

ABSTRACT

OBJECTIVES: Anticholinergic burden is detrimental to cognitive health. Multiple studies found that a high anticholinergic burden is associated with an increased risk for dementia, changes to the brain structure, function, and cognitive decline. We performed a post hoc analysis of a randomized controlled deprescribing trial. We compared the effect of the intervention on baseline anticholinergic burden across the treatment and control groups and the time of recruitment before and after a lockdown due to the COVID pandemic with subgroup analyses by baseline frailty index.

DESIGN: Randomized controlled trial.

SETTINGS AND PARTICIPANTS: We analyzed data from a de-prescribing trial of older adults (>65 years) previously conducted in New Zealand that was focused on reducing the Drug Burden Index (DBI).

METHODS: We used the anticholinergic cognitive burden (ACB) to quantify the impact of the intervention on reducing the anticholinergic burden. Participants not taking anticholinergics at the start of the trial were excluded. The primary outcome for this subgroup analysis was a change in ACB, measured with the ĝHedges statistic describing the difference in standard deviation units of this change between intervention and control. For this analysis, the trial participants were stratified into low, medium, and high frailty and timing into prior- and post-lockdown (public health measures for COVID-19).

RESULTS: Among the 295 participants in this analysis, the median (IQR) age was 79 (74, 85), and 67% were women. For the primary outcome ĝHedges = -0.04 (95% CI -0.26 to 0.19) with a -0.23 mean reduction in ACB in the intervention arm and -0.19 in the control arm. Before lockdown ĝHedges = -0.38 (95% CI -0.84 to 0.04) and post-lockdown ĝHedges = 0.07 (95% CI -0.19 to 0.33). The mean change in ACB for each of the frailty strata was as follows: low frailty (-0.02; 95% CI -0.65 to 0.18); medium frailty (0.05; 95% CI -0.28 to 0.38); high frailty (0.08; 95% CI -0.40 to 0.56).

CONCLUSIONS AND IMPLICATIONS: The study did not provide evidence for the effect of pharmacist deprescribing intervention on reducing the anticholinergic burden. However, this post hoc analysis examined the impact of COVID on the effectiveness of the intervention, and further research in this area may be warranted.

PMID:37339754 | DOI:10.1016/j.jamda.2023.05.014

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Nevin Manimala Statistics

Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case report/series

Int J Antimicrob Agents. 2023 Jun 18:106895. doi: 10.1016/j.ijantimicag.2023.106895. Online ahead of print.

ABSTRACT

INTRODUCTION: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not been standardized yet. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful cases of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, we evaluated the antipyretic effect of TC+FQ.

METHODS: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In the cases where we were able to extract temperature data, after homogenizing patient characteristics, we evaluated the time-dependent changes in the fever type from the date of the first visit for the TC and TC+FQ groups.

RESULTS: The primary search yielded 182 cases, with the individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group), which included the temperature data. The TC+FQ group had significantly lower body temperatures as compared to the TC group from day 3 to day 4.

CONCLUSIONS: Although TC monotherapy for JSF can produce defervescence after a while, the fever duration is longer as compared to other rickettsial infections, such as scrub typhus. Results suggest that TC+FQ was more effective for the antipyretic effect, with a potential shortening of the duration that patients suffer from the febrile symptoms.

PMID:37339710 | DOI:10.1016/j.ijantimicag.2023.106895

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Nevin Manimala Statistics

How Does Dynamic Arthroscopic Tracking Compare With Radiological Glenoid Track for Identification of On- and Off- Track Lesions in anterior shoulder instability

J Shoulder Elbow Surg. 2023 Jun 18:S1058-2746(23)00456-1. doi: 10.1016/j.jse.2023.05.018. Online ahead of print.

ABSTRACT

BACKGROUND: Current treatment paradigms for anterior shoulder instability are based on radiological measurements of glenohumeral bone defects, and mathematical calculation of glenoid track is used to classify lesions into “on-track”, and “off-track” morphology. However, radiological measurements have shown high variability, and glenoid track widths under dynamic conditions have been reported to be significantly smaller than those under static radiological conditions. The purpose of this study was to assess the reliability, reproducibility, and diagnostic validity of dynamic arthroscopic standardized tracking (DAST) in comparison with the gold-standard radiological track measurement method for identification of on/off-track bony lesions in patients with anteroinferior shoulder instability METHODS: Between January 2018 and 2022, 114 patients with traumatic anterior shoulder instability were evaluated using 3T MRI or CT scans; glenoid bone loss (GBL), Hill-Sachs interval (HSI), glenoid track (GT), and Hill-Sach’s occupancy ratio (HSO) were measured, and defects were classified as on- or off-track, and peripheral-track (HSO%) by two independent researchers. During arthroscopy, a standardized method (DAST) was used to classify defects into on-track (central and peripheral), and off-track by two independent observers. Interobserver reliability for DAST and radiological method was calculated using Kappa statistics and reported as percent agreement. Diagnostic validity (sensitivity, specificity, positive predictive value, and negative predictive value) of DAST was calculated using the radiological (HSO%) track as gold standard.

RESULTS: Radiologically measured mean GBL, HSI, GT, and HSO for off-track lesions were lower in arthroscopically classified off-track lesions (DAST) as compared with radiological method. DAST showed near-perfect agreement between 2 observers for on-off track classification (k=0.96, p<0.001) as well as for on-peripheral-off track classification (k=0.88, p<0.001). Radiological method showed greater interobserver variability (0.31, 0.24) with only fair agreement for both classifications. Inter-method agreement varied between 71% and 79% (CI 62-86%) between the 2 observers, and reliability was assessed as slight to fair (K=0.38, 0.16). Overall, for identification of an off-track lesion, DAST showed maximum specificity (81%, 78%) when radiological peripheral-track lesions (HSO% 75-100) were considered as off-track, and maximum sensitivity when arthroscopic peripheral track lesions were classified as off-track.

CONCLUSION: Although the intermethod agreement was low, a standardized arthroscopic tracking method (DAST) showed superior interobserver agreement and reliability for lesion classification in comparison with radiological track method. Incorporating DAST in current algorithms may help reduce variability in surgical decision-making.

PMID:37339701 | DOI:10.1016/j.jse.2023.05.018

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Connectopic mapping techniques do not reflect functional gradients in the brain

Neuroimage. 2023 Jun 18:120228. doi: 10.1016/j.neuroimage.2023.120228. Online ahead of print.

ABSTRACT

Functional gradients, in which response properties change gradually across a brain region, have been proposed as a key organising principle of the brain. Recent studies using both resting-state and natural viewing paradigms have indicated that these gradients may be reconstructed from functional connectivity patterns via “connectopic mapping” analyses. However, local connectivity patterns may be confounded by spatial autocorrelations artificially introduced during data analysis, for instance by spatial smoothing or interpolation between coordinate spaces. Here, we investigate whether such confounds can produce illusory connectopic gradients. We generated datasets comprising random white noise in subjects’ functional volume spaces, then optionally applied spatial smoothing and/or interpolated the data to a different volume or surface space. Both smoothing and interpolation induced spatial autocorrelations sufficient for connectopic mapping to produce both volume- and surface-based local gradients in numerous brain regions. Furthermore, these gradients appeared highly similar to those obtained from real natural viewing data, although gradients generated from real and random data were statistically different in certain scenarios. We also reconstructed global gradients across the whole-brain – while these appeared less susceptible to artificial spatial autocorrelations, the ability to reproduce previously reported gradients was closely linked to specific features of the analysis pipeline. These results indicate that previously reported gradients identified by connectopic mapping techniques may be confounded by artificial spatial autocorrelations introduced during the analysis, and in some cases may reproduce poorly across different analysis pipelines. These findings imply that connectopic gradients need to be interpreted with caution.

PMID:37339700 | DOI:10.1016/j.neuroimage.2023.120228

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Nevin Manimala Statistics

Feasibility of Cerebellar Measurements with Phased-Array Sonography through the Anterior Fontanelle in Comparison to MRI

Am J Perinatol. 2023 Jun 20. doi: 10.1055/a-2113-8528. Online ahead of print.

ABSTRACT

OBJECTIVE: Cerebral sonography through the anterior fontanelle is a neonatal brain imaging method that has become an integral part of modern neonatal bedside care for both screening and diagnostic purposes. Premature infants with cognitive delay have a reduction in cerebellar size at term corrected age on MRI. We aimed to determine the level of agreement between postnatal MRI and cerebral sonography for cerebellar biometry and to determine the level of agreement within one and between different examiners.

STUDY DESIGN: Cerebellar sonography and MRI measurements of the cerebellum from 30 term infants was assessed by Bland-Altman plots. Measurements between both modalities were compared using Wilcoxon Signed-Rank Test. A p-value < 0.01 was considered statistically significant. Intra-class correlation coefficients (ICC) for intra-rater and inter-rater reliability of cerebral sonography measurements were calculated.

RESULTS: There was no statistically significant difference between cerebral sonography and MRI for linear measurements, but the measurements of perimeter and surface area differed significantly between the two techniques. There was a systematic bias between both modalities for most measurements except for anterior-posterior width and vermis height. For measurements that were not statistically different from MRI we found excellent intra-rater ICC for the anterior-posterior width, vermis height and cerebellar width. The inter-rater ICC was excellent for the anterior-posterior width and vermis height, but poor for the transverse cerebellar width.

CONCLUSIONS: With a strict imaging protocol cerebellar measurements of the anterior-posterior width and the vermis height can be used as an alternative to MRI for diagnostic-screening purposes in a neonatal department where multiple clinicians perform bedside cerebral sonography.

PMID:37339678 | DOI:10.1055/a-2113-8528

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Nevin Manimala Statistics

Associations Between Anemia and Outcomes of Pregnant Patients with Pyelonephritis

Am J Perinatol. 2023 Jun 20. doi: 10.1055/a-2113-2892. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to determine if pregnant patients with both pyelonephritis and anemia are at an increased risk of adverse maternal outcomes compared to those with pyelonephritis without anemia.

STUDY DESIGN: We conducted a retrospective cohort study utilizing the Nationwide Readmissions Database (NRD). Patients with antepartum pyelonephritis-associated hospitalizations from 10/15-12/18 were included. International Classification of Diseases codes were used to identify pyelonephritis, anemia, maternal comorbidities, and severe maternal morbidities. The primary outcome was a composite of severe maternal morbidity, as defined by Centers for Disease Control criteria. Univariate statistical methods, weighted to account for complex survey methods in the NRD, were used to assess for associations between anemia, baseline characteristics, and patient outcomes. Weighted logistic and Poisson regressions were used to assess for associations between anemia and outcomes, adjusting for clinical co-morbidities and other confounding factors.

RESULTS: In total, 29,296 pyelonephritis admissions were identified, corresponding to a weighted national estimate of 55,135 admissions. Of these, 11,798 (21.3%) were anemic. The rate of severe maternal morbidity was higher among anemic patients than non-anemic patients (27.8% vs 8.9%, respectively, p<0.001), and remained higher after adjustment (adjusted relative risk (aRR) 2.86 (95% CI: 2.67, 3.06)). Rates of individual components of severe maternal morbidities, including acute respiratory distress syndrome (4.0% vs 0.6%,aRR 3.97 (95% CI: 3.10, 5.08), sepsis (22.5% vs 7.9%,aRR 2.64 (95% CI: 2.45, 2.85)), shock (4.5% vs 0.6%,aRR 5.48 (95% CI: 4.32, 6.95)), and acute renal failure (2.9% vs 0.8%,aRR 1.99 (95% CI: 1.55, 2.55)) were all higher for anemic pyelonephritis. The mean length of stay was also longer (25% average increase, (95% CI: 22%, 28%)).

CONCLUSION: Among pregnant patients with pyelonephritis, those with anemia are at greater risk of severe maternal morbidity and longer hospital stay.

PMID:37339672 | DOI:10.1055/a-2113-2892

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Nevin Manimala Statistics

Carbon Dioxide Level between Nasal High-Frequency Oscillatory Ventilation and Synchronized Nasal Intermittent Positive Pressure Ventilation after Extubation in Neonates: A Crossover Randomized Controlled Trial

Am J Perinatol. 2023 Jun 20. doi: 10.1055/a-2113-3284. Online ahead of print.

ABSTRACT

OBJECTIVE: Nasal high-frequency oscillatory ventilation (nHFOV) and synchronized nasal intermittent positive pressure ventilation (sNIPPV) yield a lower partial pressure of CO2 (pCO2) after extubation than nasal continuous positive airway pressure. Our aim was to clarify which of the two was superior.

STUDY DESIGN: We performed a crossover randomized study to evaluate pCO2 level among 102 participants from July 2020 to June 2022. Intubated preterm and term neonates with arterial lines were randomly allocated to nHFOV-sNIPPV or sNIPPV-nHFOV sequences; their pCO2 levels were measured after 2 h in each mode. Subgroup analyses were performed for preterm (gestational age <37 weeks) and very preterm (gestational age <32 weeks) neonates. Results The mean gestational age (nHFOV-sNIPPV, 32.8 vs sNIPPV-nHFOV, 33.5 weeks) and median birth weight (1,850 vs 1,930 g) did not differ between the sequences. The mean ± standard deviation pCO2 level after nHFOV (38.7 ± 8.8 mmHg) was significantly higher than that after sNIPPV (36.8 ± 10.2 mmHg; mean difference: 1.9 mmHg; 95% confidence interval: 0.3-3.4; treatment effect [p = 0.007] but no sequence [p = 0.92], period [p = 0.53], or carryover [p = 0.94] effects). However, the difference of pCO2 level between the sequences was not statistically significant in the subgroup analyses of preterm and very preterm neonates. Conclusion After neonatal extubation, the sNIPPV mode was associated with a lower pCO2 level than the nHFOV mode with no significant difference in preterm and very preterm neonates.

PMID:37339671 | DOI:10.1055/a-2113-3284

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Are there any volume-related effects on treatment options for patients with penile cancer? Results of a survey among university hospitals in Germany and Austria

Aktuelle Urol. 2023 Jun 20. doi: 10.1055/a-2090-5199. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, 959 men in Germany and 67 in Austria are diagnosed with penile cancer each year, with an increase of approximately 20% in the last decade [RKI 2021, Statcube.at 2023]. Despite the rising incidence, the number of cases per hospital remains low. The median annual number of penile cancer cases at university hospitals in the DACH region was 7 patients (IQR 5-10) in 2017 [E-PROPS group 2021]. The compromised institutional expertise due to low case numbers is compounded with inadequate adherence to penile cancer guidelines, as shown in several studies. The centralization, which is rigorously implemented in countries such as the UK, enabled a significant increase in organ-preserving primary tumor surgery and stage-adapted lymphadenectomies, as well as improved patient survival in cases of penile cancer, resulting in a claim for a similar centralization in Germany and Austria. The aim of this study was to determine the current effects of case volume on penile cancer related treatment options at university hospitals in Germany and Austria.

MATERIALS AND METHODS: In January 2023, a survey was sent to the heads of 48 urological university hospitals in Germany and Austria, including questions regarding case volume in 2021 (total number of inpatient and penile cancer cases), treatment options for primary tumors and inguinal lymphadenectomy (ILAE), the availability of a designated penile cancer surgeon, and the professional responsibility for systemic therapies in penile cancer. Correlations and differences related to case volume were statistically analyzed without adjustments.

RESULTS: The response rate was 75% (n=36/48). In total, 626 penile cancer patients were treated at the 36 responding university hospitals in 2021, representing approximately 60% of the expected incidence in Germany and Austria. The annual median total number of cases was 2807 (IQR 1937-3653), and for penile cancer, it was 13 (IQR 9-26). There was no significant correlation between the total inpatient and penile cancer caseloads (p=0.34). The number of organ-preserving therapy procedures for the primary tumor, the availability of modern ILAE procedures, the presence of a designated penile cancer surgeon, and the responsibility for systemic therapies were not significantly influenced by the total inpatient or penile cancer case volume of the treating hospitals, regardless of whether the case volumes were dichotomized at the median or upper quartile. No significant differences between Germany and Austria were observed.

CONCLUSION: Despite a significant increase in the annual number of penile cancer cases at university hospitals in Germany and Austria compared to 2017, we found no case volume-related effects on structural quality with respect to penile cancer therapy. In the light of the proven benefits of centralization, we interpret this result as an argument for the necessity of establishing nationally organized penile cancer centers with even higher case volumes compared to the status quo, in light of the proven benefits of centralization.

PMID:37339667 | DOI:10.1055/a-2090-5199

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Effect of Combined Training on Body Image, Body Composition and Functional Capacity in Patients with Breast Cancer: Controlled Clinical Trial

Rev Bras Ginecol Obstet. 2023 May;45(5):242-252. doi: 10.1055/s-0043-1770126. Epub 2023 Jun 20.

ABSTRACT

OBJECTIVE: Evaluate the effect of combined training on body image (BI), body composition and functional capacity in patients with breast cancer. As also the relationship of BI with body composition and functional capacity.

METHODS: This was a Controlled Clinical Trial study, this study including 26 patients with breast cancer (30 to 59 years). The training group (n = 13) underwent 12 weeks of training, including three 60-min sessions of aerobic exercise and resistance training, and two sessions of flexibility training per week; each flexibility exercise lasted 20s. The Control Group (n = 13) received only the standard hospital treatment. Participants were evaluated at baseline and after 12 weeks. BI (primary outcomes) was assessed using the Body Image After Breast Cancer Questionnaire; Body composition was estimated with the indicators: Body mass index; Weight, Waist hip Ratio; Waist height ratio; Conicity index; Reciprocal ponderal index; Percentage of fat; Circumference of the abdomen and waist; Functional capacity by cardiorespiratory fitness (cycle ergometer) and strength (manual dynamometer). The statistic was performed in the Biostatistics and Stata 14.0 (α = 5%).

RESULTS: The patients in the training group showed a reduction in the limitation dimension (p = 0.036) on BI, However, an increase in waist circumference was observed in both groups. In addition an increase in VO2max (p < 0.001) and strength in the right (p = 0.005) and left arms (p = 0.033).

CONCLUSION: Combined training demonstrates to be an effective and non-pharmacological strategy to patients with breast cancer, with improvement on BI and functional capacity, changing related variables negatively when there is no physical training.

PMID:37339643 | DOI:10.1055/s-0043-1770126