Nevin Manimala Statistics

Childhood prevalence of achondroplasia in New South Wales and the Australian Capital Territory, Australia

Am J Med Genet A. 2021 Feb 27. doi: 10.1002/ajmg.a.62142. Online ahead of print.


The aim of this study was to estimate the childhood prevalence of achondroplasia, trends over time in birth prevalence, and age at diagnosis in Australia. Children born between 1990 and 2019 with a clinical and radiological and/or molecular diagnosis of achondroplasia were identified from a tertiary hospital servicing New South Wales (NSW) and the Australian Capital Territory (ACT) and compared with population data from the Australian Bureau of Statistics. Childhood prevalence of achondroplasia, based on children ≤19 years of age and resident in NSW/ACT on June 30, 2019 (n = 109), was 5.2 per 100,000. A total of 127 individuals with achondroplasia were born in 1990-2019 in NSW/ACT. Birth prevalence rates increased across birth decades, from 3.3 per 100,000 live births in 1990-1999 to 5.3 per 100,000 in 2010-2019 (p < 0.0001). Median age at diagnosis decreased to 17 days in 2010-2019 compared with 30 days in 1990-1999 (p = 0.035), although the overall decreasing trend across consecutive decades did not reach statistical significance. This is the first study to show a rising birth prevalence rate for achondroplasia in Australia with a concurrent decreasing age at diagnosis, both of which were statistically significant after 2 decades.

PMID:33638607 | DOI:10.1002/ajmg.a.62142

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LI-RADS Major Features on MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

J Magn Reson Imaging. 2021 Feb 27. doi: 10.1002/jmri.27570. Online ahead of print.


BACKGROUND: The reported diagnostic performance for hepatocellular carcinoma (HCC) of each major imaging feature on MRI using standardized definitions of the Liver Imaging Reporting and Data System (LI-RADS) is variable. It is important to know the actual performance of each LI-RADS major imaging feature for imaging diagnosis of HCC and determine the sources of heterogeneity between the reported results.

PURPOSE: To systematically determine the performance of each major imaging feature of LI-RADS for diagnosing HCC using either extracellular contrast agent-enhanced MRI (ECA-MRI) or gadoxetate disodium-enhanced MRI (EOB-MRI).

STUDY TYPE: Systematic review and meta-analysis.

SUBJECTS: Sixteen original articles with 3542 lesions.

FIELD STRENGTH: A 1.5 T and 3.0 T.

ASSESSMENT: Data extraction was independently performed by two reviewers who identified and reviewed original articles reporting the diagnostic performance of each LI-RADS major imaging feature-arterial phase hyperenhancement (APHE), observation size, washout appearance, enhancing “capsule,” and threshold growth-using MRI. Study characteristics, study population characteristics, MRI characteristics, contrast agent, LI-RADS version, reference standards, and study outcomes were extracted from included studies. Risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

STATISTICAL TESTS: Bivariate random-effects models were used to obtain summary estimates of the diagnostic performance of each LI-RADS major imaging feature. Hierarchical summary receiver operating characteristic curves were plotted. Meta-regression analyses were performed to explore potential sources of heterogeneity.

RESULTS: The pooled per-observation sensitivities and specificities for diagnosing HCC were 85% (95% confidence interval [CI] = 78%-89%) and 57% (95% CI = 44%-70%) for arterial phase hyperenhancement (APHE), 77% (95% CI = 72%-82%), and 74% (95% CI = 63%-83%) for washout appearance, and 52% (95% CI = 41%-64%) and 90% (95% CI = 85%-94%) for enhancing “capsule,” respectively.

DATA CONCLUSIONS: Among the LI-RADS major features, the sensitivity was the highest for APHE and the specificity was the highest for enhancing “capsule” in the diagnosis of HCC.


PMID:33638582 | DOI:10.1002/jmri.27570

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Multiparametric MRI-Based Radiomics Approaches for Preoperative Prediction of EGFR Mutation Status in Spinal Bone Metastases in Patients with Lung Adenocarcinoma

J Magn Reson Imaging. 2021 Feb 27. doi: 10.1002/jmri.27579. Online ahead of print.


BACKGROUND: Preoperative prediction of epidermal growth factor receptor (EGFR) mutation status in patients with spinal bone metastases (SBM) from primary lung adenocarcinoma is potentially important for treatment decisions.

PURPOSE: To develop and validate multiparametric magnetic resonance imaging (MRI)-based radiomics methods for preoperative prediction of EGFR mutation based on MRI of SBM.

STUDY TYPE: Retrospective.

POPULATION: A total of 97 preoperative patients with lumbar SBM from lung adenocarcinoma (77 in training set and 20 in validation set).

FIELD STRENGTH/SEQUENCE: T1-weighted, T2-weighted, and T2-weighted fat-suppressed fast spin echo sequences at 3.0 T.

ASSESSMENT: Radiomics handcrafted and deep learning-based features were extracted and selected from each MRI sequence. The abilities of the features to predict EGFR mutation status were analyzed and compared. A radiomics nomogram was constructed integrating the selected features.

STATISTICAL TESTS: The Mann-Whitney U test and χ2 test were employed for evaluating associations between clinical characteristics and EGFR mutation status for continuous and discrete variables, respectively. Least absolute shrinkage and selection operator was used for selection of predictive features. Sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristic curve (AUC) were used to evaluate the ability of radiomics models to predict the EGFR mutation. Calibration and decision curve analysis (DCA) were performed to assess and validate nomogram results.

RESULTS: The radiomics signature comprised five handcrafted and one deep learning-based features and achieved good performance for predicting EGFR mutation status, with AUCs of 0.891 (95% confidence interval [CI], 0.820-0.962, SEN = 0.913, SPE = 0.710) in the training group and 0.771 (95% CI, 0.551-0.991, SEN = 0.750, SPE = 0.875) in the validation group. DCA confirmed the potential clinical usefulness of the radiomics models.

DATA CONCLUSION: Multiparametric MRI-based radiomics is potentially clinical valuable for predicting EGFR mutation status in patients with SBM from lung adenocarcinoma.


PMID:33638577 | DOI:10.1002/jmri.27579

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Comparison of Carotid Plaque Characteristics Between Men and Women Using Magnetic Resonance Vessel Wall Imaging: A Chinese Atherosclerosis Risk Evaluation Study

J Magn Reson Imaging. 2021 Feb 27. doi: 10.1002/jmri.27576. Online ahead of print.


BACKGROUND: Carotid vulnerable plaque is a major cause of stroke and differs between men and women. Few studies have investigated the differences in carotid plaque features between sexes in a Chinese population.

PURPOSE: To compare carotid atherosclerotic plaque features between men and women in a Chinese population using magnetic resonance imaging.

STUDY TYPE: Cross-sectional.

SUBJECTS: A total of 567 patients (mean age: 61.5 ± 10.1 years; 404 men) who had recent stroke or transient ischemia attack and atherosclerotic plaque in at least one carotid artery.


SEQUENCE: T1- and T2-weighted turbo spin echo, three-dimensional time-of-flight (TOF) fast field echo and magnetization-prepared rapid acquisition gradient echo sequences.

ASSESSMENT: Plaque characteristics including lumen area (LA), wall area (WA), total vessel area (TVA), mean wall thickness (MWT), and mean normalized wall index (NWI); presence of calcification, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture (FCR); and percent composition area (%area) were evaluated and compared between men and women.

STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, chi-square test, and multiple linear and logistic regressions.

RESULTS: In symptomatic arteries, men had significantly greater LA (46.2 ± 15.6 mm2 vs. 40.7 ± 12.9 mm2 , P < 0.05), WA (33.9 ± 11.5 mm2 vs. 26.3 ± 7.5 mm2 , P < 0.05), and TVA (80.1 ± 20.4 mm2 vs. 67.0 ± 18.0 mm2 , P < 0.05); higher MWT (1.2 ± 0.4 mm vs. 1.0 ± 0.2 mm, P < 0.05); and higher prevalence of LRNC (72.3% vs. 46.0%, P < 0.05) and IPH (18.6% vs. 4.9%, P < 0.05) compared with women. In asymptomatic arteries, men had significantly greater LA (48.3 ± 16.9 mm2 vs. 42.1 ± 12.6 mm2 , P < 0.05), WA (32.9 ± 11.0 mm2 vs. 25.8 ± 6.1 mm2 , P < 0.05), and TVA (81.2 ± 22.1 mm2 vs. 67.9 ± 16.5 mm2 , P < 0.05); higher MWT (1.2 ± 0.3 mm vs. 1.0 ± 0.2 mm, P < 0.05); higher prevalence of LRNC (67.8% vs. 42.9%, P < 0.05), IPH (14.9% vs. 1.2%, P < 0.05), and FCR (6.4% vs. 1.2%, P < 0.05); and higher %LRNC area (24.8 ± 17.2% vs. 17.8 ± 14.1%, P < 0.05) compared with women.

DATA CONCLUSION: Men have similar plaque burden but more vulnerable atherosclerotic plaques compared with women in both symptomatic and asymptomatic carotid arteries in a Chinese population.


PMID:33638575 | DOI:10.1002/jmri.27576

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Cohort profile: SARS-CoV-2/COVID-19 hospitalised patients in Switzerland

Swiss Med Wkly. 2021 Feb 15;151:w20475. doi: 10.4414/smw.2021.20475. eCollection 2021 Feb 15.


BACKGROUND: SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020.

AIM: In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system.

METHODS: Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient&rsquo;s admission date.

RESULTS: As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54&ndash;79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults.

CONCLUSION: The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

PMID:33638351 | DOI:10.4414/smw.2021.20475

Nevin Manimala Statistics

HeteroGGM: an R package for Gaussian graphical model-based heterogeneity analysis

Bioinformatics. 2021 Feb 26:btab134. doi: 10.1093/bioinformatics/btab134. Online ahead of print.


SUMMARY: Heterogeneity is a hallmark of many complex human diseases, and unsupervised heterogeneity analysis has been extensively conducted using high-throughput molecular measurements and histopathological imaging features. “Classic” heterogeneity analysis has been based on simple statistics such as mean, variance, and correlation. Network-based analysis takes interconnections as well as individual variable properties into consideration and can be more informative. Several Gaussian graphical model (GGM)-based heterogeneity analysis techniques have been developed, but friendly and portable software is still lacking. To facilitate more extensive usage, we develop the R package HeteroGGM, which conducts GGM-based heterogeneity analysis using the advanced penaliztaion techniques, can provide informative summary and graphical presentation, and is efficient and friendly.

AVAILABILITY: The package is available at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:33638346 | DOI:10.1093/bioinformatics/btab134

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Using machine learning to improve the accuracy of patient deterioration predictions: Mayo Clinic Early Warning Score (MC-EWS)

J Am Med Inform Assoc. 2021 Feb 26:ocaa347. doi: 10.1093/jamia/ocaa347. Online ahead of print.


OBJECTIVE: We aimed to develop a model for accurate prediction of general care inpatient deterioration.

MATERIALS AND METHODS: Training and internal validation datasets were built using 2-year data from a quaternary hospital in the Midwest. Model training used gradient boosting and feature engineering (clinically relevant interactions, time-series information) to predict general care inpatient deterioration (resuscitation call, intensive care unit transfer, or rapid response team call) in 24 hours. Data from a tertiary care hospital in the Southwest were used for external validation. C-statistic, sensitivity, positive predictive value, and alert rate were calculated for different cutoffs and compared with the National Early Warning Score. Sensitivity analysis evaluated prediction of intensive care unit transfer or resuscitation call.

RESULTS: Training, internal validation, and external validation datasets included 24 500, 25 784 and 53 956 hospitalizations, respectively. The Mayo Clinic Early Warning Score (MC-EWS) demonstrated excellent discrimination in both the internal and external validation datasets (C-statistic = 0.913, 0.937, respectively), and results were consistent in the sensitivity analysis (C-statistic = 0.932 in external validation). At a sensitivity of 73%, MC-EWS would generate 0.7 alerts per day per 10 patients, 45% less than the National Early Warning Score.

DISCUSSION: Low alert rates are important for implementation of an alert system. Other early warning scores developed for the general care ward have achieved lower discrimination overall compared with MC-EWS, likely because MC-EWS includes both nursing assessments and extensive feature engineering.

CONCLUSIONS: MC-EWS achieved superior prediction of general care inpatient deterioration using sophisticated feature engineering and a machine learning approach, reducing alert rate.

PMID:33638343 | DOI:10.1093/jamia/ocaa347

Nevin Manimala Statistics

Is BMI a Factor in Compliance to Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

Chirurgia (Bucur). 2021 Jan-Feb;116(1):51-59. doi: 10.21614/chirurgia.116.1.51.


Background: Compliance to adjuvant chemotherapy (AC) for patients undergoing rectal surgery ranges from 43% to 73.6%. Reasons reported for not initiating or completing AC include onset of postoperative complications, drug toxicity, disease progression and/or patient preferences. Little is known regarding the impact of obesity on the compliance to AC in this setting. Methods: This multicenter, retrospective study analyzed compliance to AC and treatment-related morbidity in 511 patients having undergone surgery with curative intent for rectal cancer in six Italian colorectal centers between January 2013 and December 2017. Results: 70 patients were obese (BMI 30 kg/m2). The proportion of open procedures (22.9% vs. 13.4%) and conversions (14.3% vs. 4.8%) was greater in obese compared to non-obese patients (p 0.001). Median hospital stay was one day longer for obese patients (9 days vs. 10 days, p=0.038) while there was no statistically significant difference in the complication rate, whether overall (58.6% in obese vs. 52.3% in non-obese) or with a Clavien-Dindo score 3 (17.1% vs 10.9%). AC was offered to 49/70 (70%) patients in the obese group and 306/441 (69.4%) in the non-obese group (p=0.43). There was no statistically significant difference in AC compliance: 18.4% and 22.9% did not start AC, while 36.7% and 34.6%, started AC but did not complete the scheduled treatment (p=0.79) in the obese and non-obese group, respectively. Overall, 55% of patients who started AC successfully completed their adjuvant treatment. Conclusions: Obesity did not impact compliance to AC for locally advanced rectal cancer: compliance was poor in obese and non-obese patients with no statistically significant difference between the two groups. Major complication rate was not statistically significantly affected by increased BMI.

PMID:33638326 | DOI:10.21614/chirurgia.116.1.51

Nevin Manimala Statistics

Determining the association between repeatedly elevated serum gamma-glutamyltransferase levels and risk of respiratory cancer: A nationwide population-based cohort study

Cancer Med. 2021 Feb 26. doi: 10.1002/cam4.3735. Online ahead of print.


BACKGROUND: Although elevated serum gamma-glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence.

METHODS: We included participants who had undergone the Korean Health screening four times during 2009-2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models.

RESULTS: During mean follow-up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31-1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81-1.11).

CONCLUSION: Repeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.

PMID:33638317 | DOI:10.1002/cam4.3735

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The quality of life in papillary thyroid microcarcinoma patients undergoing lobectomy or total thyroidectomy: A cross-sectional study

Cancer Med. 2021 Feb 26. doi: 10.1002/cam4.3747. Online ahead of print.


OBJECTIVE: Papillary thyroid microcarcinoma (PTMC) has a good prognosis and a long survival time, surgery is the common treatment including total thyroidectomy (TT) and unilateral lobectomy (LT), but recent studies showed that TT does not show an advantage over LT for PTMC in preventing cancer recurrence and reducing mortality. Given this, the health-related quality of life (HRQoL) has become one of the important factors that physicians must consider when making treatment decisions. The aim of this study was to compare the HRQoL of patients between undergoing TT and LT.

METHODS: From October 2019 to December 2019, 69 PTMC patients were enrolled in our study, including 34 in the LT group and 35 in the TT group, respectively. We used three questionnaires which included the 36-item short-form health survey (SF-36), thyroid cancer-specific quality of life (THYCA-QOL), and Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for each patient to evaluate their scores of HRQoL.

RESULTS: According to the SF-36, the scores of the domain for the role limitation due to physical problems, emotional problems, and social function (RP, RE, and SF) as well as Physical Component Summary (PCS) and Mental Component Summary (MCS) showed a significant negative linear association between the LT group and TT group: RP (coefficient [coef]: -33.953 [confidence interval (CI) -51.187 to -16.720], p < 0.001, RE (coef: -21.633 [CI -39.500 to -3.766], p = 0.018), SF (coef: -10.169 [CI -19.586 to -0.752], p = 0.035)and PCS (coef: -10.571 [CI -17.768 to -3.373], p = 0.005), MCS (coef: -10.694 [CI -19.465 to -1.923], p = 0.018). The THYCA-QOL showed that the scores of the TT group were higher than that of the LT group in the problem of scar (coef: 16.245 [CI 1.697 to 30.794], p = 0.029 according to the multivariate analysis), suggesting a higher level of complaint in the TT group. There was no statistically significant difference in the scores of FoP-Q-SF between the two groups.

CONCLUSIONS: In patients with PTMC, LT offers an advantage over TT in terms of HRQoL, which supports the role of LT as an alternative strategy to TT.

PMID:33638269 | DOI:10.1002/cam4.3747