Tag: statistics

Braz J Psychiatry. 2023 May 27. doi: 10.47626/1516-4446-2023-3037. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore differences in regional cortical morphometric structure between adolescents at risk for depression or with current depression.

METHODS: We analyzed cross-sectional structural neuroimaging data from a sample of 150 Brazilian adolescents classified as low-risk (n=50) or high-risk for depression (n=50) or with current depression (n=50) through a vertex-based approach with measurements of cortical volume, surface area and thickness. Differences between groups in subcortical volumes and in the organization of networks of structural covariance were also explored.

RESULTS: No significant differences in brain structure between groups were observed in whole-brain vertex-wise cortical volume, surface area or thickness. Also, no significant differences in subcortical volume were observed between risk groups. In relation to the structural covariance network, there was an indication of an increase in the hippocampus betweenness centrality index in the high-risk group network compared to the low-risk and current depression group networks. However, this result was only statistically significant when applying false discovery rate correction for nodes within the affective network.

CONCLUSION: In an adolescent sample recruited using an empirically based composite risk score, no major differences in brain structure were detected according to the risk and presence of depression.

PMID:37243979 | DOI:10.47626/1516-4446-2023-3037

Pediatr Blood Cancer. 2023 May 27:e30452. doi: 10.1002/pbc.30452. Online ahead of print.

ABSTRACT

PURPOSE/OBJECTIVE: We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL).

MATERIALS/METHODS: Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MR_CXR ) > 1/3; (ii) mediastinal mass ratio on CT (MR_CT ) > 1/3; (iii) mediastinal mass volume on CT (MV_CT ) > 200 mL; (iv) normalized mediastinal mass volume (MV_CT /thoracic diameter [TD]) > 1 mL/mm; (v) mediastinal mass diameter on CT (MD_CT ) > 10 cm; and (vi) normalized mediastinal mass diameter (MD_CT /TD) > 1/3.

RESULTS: Median age at diagnosis was 15.8 years (range: 5.2-21.3 years). In patients with a slow early response (SER) to chemotherapy, MV_CT > 200 mL, MD_CT > 10 cm, and MD_CT /TD > 1/3 were associated with worse relapse-free survival (RFS) on MVA, while MR_CXR > 1/3, MR_CT > 1/3, and MV_CT /TD > 1 mL/mm trended toward worse RFS; MD_CT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MD_CT /TD > 1/3 versus ≤1/3 on MVA (p = .02).

CONCLUSION: LMA according to MV_CT > 200 mL, MD_CT > 10 cm, and MD_CT /TD > 1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MD_CT /TD > 1/3 appears to be the strongest predictor of inferior RFS.

PMID:37243975 | DOI:10.1002/pbc.30452

Int J Immunogenet. 2023 May 27. doi: 10.1111/iji.12623. Online ahead of print.

ABSTRACT

Behçet’s disease (BD) is a chronic auto inflammatory disorder of unknown aetiology. Recently, the dysregulation of interleukin-21 receptor (IL-21R) has been incriminated in different autoimmune and auto-inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis, and type 1 diabetes. Herein, we aimed to investigate the association of two Il-21R gene polymorphisms with BD. IL-21R rs2214537 and IL-21R rs2285452 genotypings were investigated in a cohort of 110 adult patients with BD and 116 age and gender unmatched healthy controls. Genotyping was performed by mutagenically separated polymerase chain reaction with newly designed primers. IL-21R rs2285452 genotypes and alleles distribution were statistically different between patients with BD and controls. GA and AA genotypes carrying the minor A allele were more frequent in patients with BD than in healthy controls (37.3% and 11.8% vs. 23.3% and 3.4%, respectively). The minor A allele was associated with an increased BD risk (odds ratios = 2.42, 95% confidence interval = 1.214.87, p = .005). IL-21R rs2214537 GG genotype was found to be associated with susceptibility to BD in the recessive model (GG vs. CC + CG; p = .046, OR = 1.91, 95% CI = 1.003.650. IL-21R rs2285452 and IL-21R rs2214537 were not in linkage disequilibrium (D’ = 0.42). The AG haplotype was more frequently observed in patients with BD than in controls (0.247 vs. 0.056, p = .0001). This study for the first time reports the association of IL-21R rs2285452 and IL-21R rs2214537 with BD. Functional studies are required to elucidate the exact role of these genetic variants.

PMID:37243939 | DOI:10.1111/iji.12623

Ann Noninvasive Electrocardiol. 2023 May 27:e13066. doi: 10.1111/anec.13066. Online ahead of print.

ABSTRACT

BACKGROUND: There is ongoing controversy regarding the prognostic value of PR prolongation among individuals free of cardiovascular diseases. It is necessary to risk-stratify this population according to other electrocardiographic parameters.

METHODS: This study is based on the Third National Health and Nutrition Examination Survey. Cox proportional hazard models were constructed and Kaplan-Meier method was used.

RESULTS: A total of 6188 participants (58.1 ± 13.1 years; 55% women) were included. The median frontal QRS axis of the entire study population was 37° (IQR: 11-60°). PR prolongation was present in 7.6% of the participants, of whom 61.2% had QRS axis ≤37°. In a multivariable-adjusted model, mortality risk was highest in the group with concomitant prolonged PR interval and QRS axis ≤37° (hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.04-1.39). In models with similar adjustment where population were reclassified depending on PR prolongation and QRS axis, prolonged PR interval and QRS axis ≤37° was still associated with increased risk of mortality (HR: 1.18; 95% CI: 1.03-1.36) compared with normal PR interval.

CONCLUSIONS: QRS axis is an important factor for risk stratification in population with PR prolongation. The extent to which this population with PR prolongation and QRS axis ≤37° is at higher risk of death compared with the population without PR prolongation.

PMID:37243938 | DOI:10.1111/anec.13066

Alzheimers Dement. 2023 May 27. doi: 10.1002/alz.13159. Online ahead of print.

ABSTRACT

OBJECTIVE: Investigation of learning slopes in early-onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early-onset dementia with and without β-amyloid positivity METHOD: Data from 310 participants in the Longitudinal Early-Onset Alzheimer’s Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determined RESULTS: Worse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric-the learning ratio (LR)-outperformed other learning slope calculations across analyses CONCLUSIONS: Learning slopes appear to be sensitive to early-onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses.

HIGHLIGHTS: Learning is impaired in amyloid-positive EOAD, beyond cognitive severity scores alone. Amyloid-positive EOAD participants perform worse on learning slopes than amyloid-negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

PMID:37243937 | DOI:10.1002/alz.13159

Clin Pharmacol Ther. 2023 May 27. doi: 10.1002/cpt.2960. Online ahead of print.

ABSTRACT

Pharmacogenomics studies how genes influence a person’s response to treatment. When complex phenotypes are influenced by multiple genetic variations with little effect, a single piece of genetic information is often insufficient to explain this variability. The application of machine learning (ML) in pharmacogenomics holds great potential; namely, it can be used to unravel complicated genetic relationships that could explain response to therapy. In this study, ML techniques were used to investigate the relationship between genetic variations affecting more than 60 candidate genes and carboplatin-, taxane-, and bevacizumab-induced toxicities in 171 patients with ovarian cancer enrolled in the MITO-16A/MaNGO-OV2A trial. Single nucleotide polymorphism (SNP) profiles were examined using ML to find and prioritise those associated with drug-induced toxicities, specifically hypertension, hematological toxicity, non-hematological toxicity, and proteinuria. The Boruta algorithm was used in cross-validation to determine the significance of SNPs in predicting toxicities. Important SNPs were then used to train eXtreme gradient boosting models. During cross-validation, the models achieved reliable performance with a Matthews correlation coefficient ranging from 0.375 to 0.410. A total of 43 SNPs critical for predicting toxicity were identified. For each toxicity, key SNPs were used to create a polygenic toxicity risk score that effectively divided individuals into high-risk and low-risk categories. In particular, compared with low-risk individuals, high-risk patients were 28- fold more likely to develop hypertension. The proposed method provided insightful data to improve precision medicine for ovarian cancer patients, which may be useful for reducing toxicities and improving toxicity management.

PMID:37243926 | DOI:10.1002/cpt.2960

Int J Comput Assist Radiol Surg. 2023 May 27. doi: 10.1007/s11548-023-02934-x. Online ahead of print.

ABSTRACT

PURPOSE: Intra-operative assessment of resection margins during oncological surgery is a field that needs improvement. Ultrasound (US) shows the potential to fulfill this need, but this imaging technique is highly operator-dependent. A 3D US image of the whole specimen may remedy the operator dependence. This study aims to compare and evaluate the image quality of 3D US between freehand acquisition (FA) and motorized acquisition (MA).

METHODS: Multiple 3D US volumes of a commercial phantom were acquired in motorized and freehand fashion. FA images were collected with electromagnetic navigation. An integrated algorithm reconstructed the FA images. MA images were stacked into a 3D volume. The image quality is evaluated following the metrics: contrast resolution, axial and elevation resolution, axial and elevation distance calibration, stability, inter-operator variability, and intra-operator variability. A linear mixed model determined statistical differences between FA and MA for these metrics.

RESULTS: The MA results in a statistically significant lower error of axial distance calibration (p < 0.0001) and higher stability (p < 0.0001) than FA. On the other hand, the FA has a better elevation resolution (p < 0.003) than the MA.

CONCLUSION: MA results in better image quality of 3D US than the FA method based on axial distance calibration, stability, and variability. This study suggests acquiring 3D US volumes for intra-operative ex vivo margin assessment in a motorized fashion.

PMID:37243918 | DOI:10.1007/s11548-023-02934-x

Pediatr Blood Cancer. 2023 May 27:e30421. doi: 10.1002/pbc.30421. Online ahead of print.

ABSTRACT

BACKGROUND: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum.

METHODS: After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated.

RESULTS: After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth.

CONCLUSION: Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH.

PMID:37243889 | DOI:10.1002/pbc.30421

Cerebellum. 2023 May 27. doi: 10.1007/s12311-023-01561-1. Online ahead of print.

ABSTRACT

The Ataxia Global Initiative (AGI) aims to serve as a platform to facilitate clinical trial readiness for the hereditary ataxias. Clinical trials for these diseases have been hampered by the lack of objective measures to study disease onset, progression, and treatment efficacy. While these issues are not unique to the genetic ataxias, the relative rarity of these diseases makes the need for such measures even more pressing to achieve statistical power in clinical trials. In this report, we have described the efforts of the AGI fluid biomarker working group (WG) in developing uniform protocols for biomarker sampling and storage, both for human and preclinical studies in mice. By reducing collection variability, we anticipate reduced noise in downstream biomarker analysis that will improve statistical power and minimize the necessary sample size. The emphasis has been on defining and standardizing the sampling and pre-analytical work-up of minimal set of biological samples, specifically blood plasma and serum, keeping in mind the need for harmonization of collection and storage that can be achieved with relatively limited cost and resources. An optional package is detailed for those centers that have the resources and commitment for additional biofluids/sample processing and storage. Finally, we have delineated similar standardized protocols for mice that will be important for preclinical studies in the field.

PMID:37243885 | DOI:10.1007/s12311-023-01561-1

Diabetes Metab Res Rev. 2023 May 27:e3652. doi: 10.1002/dmrr.3652. Online ahead of print.

ABSTRACT

AIMS: Prevention of foot ulcers in persons with diabetes is important to help reduce the substantial burden on both individual and health resources. A comprehensive analysis of reported interventions is needed to better inform healthcare professionals about effective prevention. The aim of this systematic review and meta-analysis is to assess the effectiveness of interventions to prevent foot ulcers in persons with diabetes who are at risk thereof.

MATERIALS AND METHODS: We searched the available scientific literature in PubMed, EMBASE, CINAHL, Cochrane databases and trial registries for original research studies on preventative interventions. Both controlled and non-controlled studies were eligible for selection. Two independent reviewers assessed risk of bias of controlled studies and extracted data. A meta-analysis (using Mantel-Haenszel’s statistical method and random effect models) was done when >1 RCT was available that met our criteria. Evidence statements, including the certainty of evidence, were formulated according to GRADE.

RESULTS: From the 19,349 records screened, 40 controlled studies (of which 33 were Randomised Controlled Trials [RCTs]) and 103 non-controlled studies were included. We found moderate certainty evidence that temperature monitoring (5 RCTs; risk ratio [RR]: 0.51; 95% CI: 0.31-0.84) and pressure-optimised therapeutic footwear or insoles (2 RCTs; RR: 0.62; 95% CI: 0.26-1.47) likely reduce the risk of plantar foot ulcer recurrence in people with diabetes at high risk. Further, we found low certainty evidence that structured education (5 RCTs; RR: 0.66; 95% CI: 0.37-1.19), therapeutic footwear (3 RCTs; RR: 0.53; 95% CI: 0.24-1.17), flexor tenotomy (1 RCT, 7 non-controlled studies, no meta-analysis), and integrated care (3 RCTs; RR: 0.78; 95% CI: 0.58-1.06) may reduce the risk of foot ulceration in people with diabetes at risk for foot ulceration.

CONCLUSIONS: Various interventions for persons with diabetes at risk for foot ulceration with evidence of effectiveness are available, including temperature monitoring (pressure-optimised) therapeutic footwear, structured education, flexor tenotomy, and integrated foot care. With hardly any new intervention studies published in recent years, more effort to produce high-quality RCTs is urgently needed to further improve the evidence base. This is especially relevant for educational and psychological interventions, for integrated care approaches for persons at high risk of ulceration, and for interventions specifically targeting persons at low-to-moderate risk of ulceration.

PMID:37243880 | DOI:10.1002/dmrr.3652