Tag: statistics

J Gynecol Oncol. 2022 Jan 17. doi: 10.3802/jgo.2022.33.e27. Online ahead of print.

ABSTRACT

OBJECTIVE: The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (POLE) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish the POLE from the copy number (CN)-low subtype in EC.

METHODS: Ninety-one samples (15 POLE, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort.

RESULTS: Body mass index (BMI) and tumor grade were significantly associated with the POLE subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the POLE from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the POLE than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683.

CONCLUSION: BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the POLE from the CN-low subtype. Cyclin B1 IHC may replace POLE sequencing in molecular classification of EC.

PMID:35128857 | DOI:10.3802/jgo.2022.33.e27

Pharm Stat. 2022 Feb 6. doi: 10.1002/pst.2196. Online ahead of print.

ABSTRACT

The document ICH E9 (R1) has brought much attention to the concept of estimand in the clinical trials community. ICH stands for International Conference for Harmonization. In this article, we draw attention to one facet of estimand that is not discussed in that document but is crucial in the context of observational studies, namely weighting for covariate balance. How weighting schemes are connected to estimand, or more specifically to one of its five attributes identified in ICH E9 (R1), the attribute of population, is illustrated using the Rubin Causal Model. Three estimands are examined from both theoretical and practical perspectives. Factors that may be considered in choosing among these estimands are discussed.

PMID:35128808 | DOI:10.1002/pst.2196

J Gynecol Oncol. 2022 Jan 17. doi: 10.3802/jgo.2022.33.e22. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the diagnostic accuracies of ultrasound and magnetic resonance imaging (MRI) for deep (≥50%) myometrial invasion (DMI) and cervical stromal invasion (CSI) in women with endometrial cancer.

METHODS: This was a prospective study at a gynecology clinic for women with postmenopausal bleeding. Between October 2015-October 2018, consecutive women with suspected endometrial cancer based on ultrasound subjective pattern recognition were simultaneously assessed for DMI and CSI on ultrasound. Subsequently, they also underwent preoperative MRI. We compared the diagnostic accuracies of ultrasound and MRI in predicting DMI and CSI with the final histology as the gold standard.

RESULTS: We included 51 women. The prevalence of DMI and CSI were 22/51 (43%) and 7/51 (14%), respectively. The majority of malignancies were of endometrioid histological subtype (38/51, 75%) and FIGO stage 1 or 2 (40/51, 78%). Ultrasound diagnosed more cases of DMI compared to MRI (19/22 vs. 17/22), however, the difference was not statistically significant. The sensitivities and specificities of ultrasound and MRI for DMI were 86% vs. 77% and 66% vs. 76%, respectively. For CSI, ultrasound and MRI correctly diagnosed the same number of cases (5/7, 71%); their respective false-positive rates were low, 0/44 (0%) and 1/44 (2%). Ultrasound and MRI had a moderate agreement for DMI (ƙ=0.49; 95% confidence interval [CI]=0.26-0.73), whereas the agreement for CSI was substantial (ƙ=0.69; 95% CI=0.36-1.00).

CONCLUSION: Endometrial cancer can be simultaneously diagnosed and staged at women’s initial ultrasound assessment. The accuracies of ultrasound for DMI and CSI are comparable to MRI.

TRIAL REGISTRATION: ISRCTN Identifier: ISRCTN24363390.

PMID:35128854 | DOI:10.3802/jgo.2022.33.e22

J Esthet Restor Dent. 2022 Feb 6. doi: 10.1111/jerd.12883. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the performance of a standardized photographic shade analysis (PSA) and visual shade matching (VSM) using two color difference formulas.

MATERIALS AND METHODS: Fifty observers (35 undergraduate and 15 graduate students) evaluated the color of two upper left central incisors (LT-light tooth, and DT-dark tooth). VSM was performed using the VITA 3D Master (3D) shade guide in a controlled clinical environment. For PSA, a cross-polarized filter and a gray card (Whibal) were used to standardize the photographs taken (target teeth and shade tabs from 3D). From the pictures obtained, the CIELAB coordinates, and color differences ( ΔEab* and ΔE₀₀ ) were obtained. The shade tabs selected by two experienced researchers were conducted as part of the pilot study, and finally used as a standard for the analysis. Data were analyzed using descriptive statistics and the chi-square test (p ≤ 0.05).

RESULTS: Shade tabs selections of VSM and PSA agreed only for LT. The best “Match” selected by the researchers agreed with data from PSA using ΔE₀₀ . PSA using ΔE₀₀ showed higher total percentages of “Match” and higher percentage of agreement among observers. A relationship was found for LT performing the PSA (p < 0.05).

CONCLUSIONS: The performance of the PSA was better than the VSM, but only when the CIEDE2000 color difference formula was used. Therefore, the color difference formulas influenced on the performance of PSA. Finally, the PSA improved the precision of the VSM.

CLINICAL SIGNIFICANCE: To use a standardized PSA to improve the VSM and shade communication in clinical esthetic dentistry.

PMID:35128799 | DOI:10.1111/jerd.12883

Pharm Stat. 2022 Feb 6. doi: 10.1002/pst.2195. Online ahead of print.

ABSTRACT

Several dynamic borrowing methods, such as the modified power prior (MPP), the commensurate prior, have been proposed to increase statistical power and reduce the required sample size in clinical trials where comparable historical controls are available. Most methods have focused on cross-sectional endpoints, and appropriate methodology for longitudinal outcomes is lacking. In this study, we extend the MPP to the linear mixed model (LMM). An important question is whether the MPP should use the conditional version of the LMM (given the random effects) or the marginal version (averaged over the distribution of the random effects), which we refer to as the conditional MPP and the marginal MPP, respectively. We evaluated the MPP for one historical control arm via a simulation study and an analysis of the data of Alzheimer’s Disease Cooperative Study (ADCS) with the commensurate prior as the comparator. The conditional MPP led to inflated type I error rate when there existed moderate or high between-study heterogeneity. The marginal MPP and the commensurate prior yielded a power gain (3.6%-10.4% vs. 0.6%-4.6%) with the type I error rates close to 5% (5.2%-6.2% vs. 3.8%-6.2%) when the between-study heterogeneity is not excessively high. For the ADCS data, all the borrowing methods improved the precision of estimates and provided the same clinical conclusions. The marginal MPP and the commensurate prior are useful for borrowing historical controls in longitudinal data analysis, while the conditional MPP is not recommended due to inflated type I error rates.

PMID:35128780 | DOI:10.1002/pst.2195

J Appl Clin Med Phys. 2022 Feb 7:e13555. doi: 10.1002/acm2.13555. Online ahead of print.

ABSTRACT

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT).

MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D_2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam-on time, were recorded.

RESULTS: Halcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate-dose spillage were observed (all, p > 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam-on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%-100%) and 98.45 ± 0.99% (range: 97.9%-100%), respectively, demonstrating similar treatment delivery accuracy.

CONCLUSION: SBRT treatment of synchronous lung lesions via single-isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic.

PMID:35128795 | DOI:10.1002/acm2.13555

J Cosmet Dermatol. 2022 Feb 6. doi: 10.1111/jocd.14697. Online ahead of print.

ABSTRACT

BACKGROUND: With an increasing demand of aesthetic soft-tissue filler treatments, the occurrence of adverse events rises likewise. An optimized injection algorithm adapted to product characteristics (eg, rheology) of the soft-tissue filler is crucial in order to ensure satisfying clinical outcomes and high patient safety.

OBJECTIVE: To identify a subjective feedback mechanism for the avoidance of adverse events after soft-tissue filler injection procedures.

METHODS: A retrospective data analysis of n = 387 aesthetic treatments performed on n = 291 patients (4 males, 287 females) with different soft-tissue fillers with regard to loss of volume (filling effect), injected layer, injectability (“ease of injection”), injected volume, and injection technique was conducted.

RESULTS: The subjectively perceived injectability during the injection process was statistically significantly related to G-Prime value with r_s = 0.101 with p = 0.048, indicating an increased difficulty while injecting products with higher G-Prime. The occurrence of adverse events was also statistically significantly related to the injectability: injections with increased subjectively perceived difficulty showed increasing odds of developing adverse events by OR 0.157 with p = 0.002.

CONCLUSION: Injections that were subjectively more difficult to perform are more likely to develop adverse events. Respecting the layered arrangement of the face, the recommended and approved depth and facial region for each specific treatment enable practitioners to achieve satisfying outcomes while keeping the rate of adverse events low.

PMID:35128773 | DOI:10.1111/jocd.14697

Trop Med Int Health. 2022 Feb 6. doi: 10.1111/tmi.13731. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze the spatial distribution of rates of COVID-19 cases and its association with socioeconomic conditions in the state of Pernambuco, Brazil.

METHODS: Autocorrelation (Moran Index) and spatial association (Geographically Weighted Regression) models were used to explain the interrelationships between municipalities and the possible effects of socioeconomic factors on rates.

RESULTS: Two isolated clusters were revealed in the inner part of the state in sparsely inhabited municipalities. The spatial model (Geographically Weighted Regression) was able to explain 50% of the variations in COVID-19 cases. The variables proportion of people with low income, percentage of rented homes, percentage of families in social programs, Gini index and running water had the greatest explanatory power for the increase in infection by COVID-19.

CONCLUSIONS: Our results provide important information on socioeconomic factors related to the spread of COVID-19 and can serve as a basis for decision-making in similar circumstances.

PMID:35128767 | DOI:10.1111/tmi.13731

J Magn Reson Imaging. 2022 Feb 7. doi: 10.1002/jmri.28098. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative imaging studies of the pancreas have often targeted the three main anatomical segments, head, body, and tail, using manual region of interest strategies to assess geographic heterogeneity. Existing automated analyses have implemented whole-organ segmentation, providing overall quantification but failing to address spatial heterogeneity.

PURPOSE: To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI.

STUDY TYPE: Retrospective.

SUBJECTS: One hundred and fifty nominally healthy subjects from UK Biobank (100 subjects for method development and 50 subjects for validation). A separate 390 UK Biobank triples of subjects including type 2 diabetes mellitus (T2DM) subjects and matched nondiabetics.

FIELD STRENGTH/SEQUENCE: A 1.5 T, three-dimensional two-point Dixon sequence (for segmentation and volume assessment) and a two-dimensional axial multiecho gradient-recalled echo sequence.

ASSESSMENT: Pancreas segments were annotated by four raters on the validation cohort. Intrarater agreement and interrater agreement were reported using Dice overlap (Dice similarity coefficient [DSC]). A segmentation method based on template registration was developed and evaluated against annotations. Results on regional pancreatic fat assessment are also presented, by intersecting the three-dimensional parts segmentation with one available proton density fat fraction (PDFF) image.

STATISTICAL TEST: Wilcoxon signed rank test and Mann-Whitney U-test for comparisons. DSC and volume differences for evaluation. A P value < 0.05 was considered statistically significant.

RESULTS: Good intrarater (DSC mean, head: 0.982, body: 0.940, tail: 0.961) agreement and interrater (DSC mean, head: 0.968, body: 0.905, tail: 0.943) agreement were observed. No differences (DSC, head: P = 0.4358, body: P = 0.0992, tail: P = 0.1080) were observed between the manual annotations and our method’s segmentations (DSC mean, head: 0.965, body: 0.893, tail: 0.934). Pancreatic body PDFF was different between T2DM and nondiabetics matched by body mass index.

DATA CONCLUSION: The developed segmentation’s performance was no different from manual annotations. Application on type 2 diabetes subjects showed potential for assessing pancreatic disease heterogeneity.

LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

PMID:35128748 | DOI:10.1002/jmri.28098

J Magn Reson Imaging. 2022 Feb 7. doi: 10.1002/jmri.28100. Online ahead of print.

ABSTRACT

BACKGROUND: Epicardial adipose tissue (EAT) may induce left atrium (LA) wall inflammation and promote LA fibrosis. Therefore, simultaneous assessment of these two important atrial fibrillation (AF) risk factors would be desirable.

PURPOSE: To perform a comprehensive evaluation of 3D Dixon water-fat separated late gadolinium enhancement (LGE-Dixon) MRI by analysis of repeatability and systematic comparison with reference methods for assessment of fibrosis and fat.

STUDY TYPE: Prospective.

POPULATION: Twenty-eight, 10, and 7 patients, respectively, with clinical indications for cardiac MRI.

FIELD STRENGTH/SEQUENCE: A 1.5-T scanner, inversion recovery multiecho spoiled gradient echo.

ASSESSMENT: Twenty-eight patients (age 58 ± 19 years, 15 males) were scanned using LGE-Dixon. A 5-point Likert-type scale was used to grade the image quality. Another 10 patients (age 46 ± 19 years, 9 males) were scanned using LGE-Dixon and 3D proton density Dixon (PD-Dixon). Finally, seven patients (age 62 ± 14 years, 4 males) were scanned using LGE-Dixon and conventional LGE. The scan time, intraobserver and interobserver variability, and levels of agreement were assessed.

STATISTICAL TESTS: Student’s t-test, one-way ANOVA, and Mann-Whitney U-test were used; P < 0.05 was considered significant, intraclass correlation coefficient (ICC).

RESULTS: The scan time (minutes:seconds) for LGE-Dixon (n = 28) was 5:01 ± 1:40. ICC values for intraobserver and interobserver measurements of LA wall fibrosis percentage were 0.98 (95% CI, 0.97-0.99) and 0.97 (95% CI, 0.94-0.99) while of EAT were 0.92 (95% CI, 0.82-0.97) and 0.90 (95% CI, 0.80-0.95). The agreement for LA fibrosis percentage between the LGE-Dixon and the conventional LGE was 0.92 (95% CI, 0.66-0.99) and for EAT volume between the LGE-Dixon and the PD-Dixon was 0.93 (95% CI, 0.72-0.98).

CONCLUSION: LA fibrosis and EAT can be assessed simultaneously using LGE-Dixon. This method allows a high level of intraobserver and interobserver repeatability as well as agreement with reference methods and can be performed in a clinically feasible scan time.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 3.

PMID:35128754 | DOI:10.1002/jmri.28100