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Nevin Manimala Statistics

Mitigation of noise-induced bias of PET radiomic features

PLoS One. 2022 Aug 25;17(8):e0272643. doi: 10.1371/journal.pone.0272643. eCollection 2022.

ABSTRACT

INTRODUCTION: One major challenge in PET radiomics is its sensitivity to noise. Low signal-to-noise ratio (SNR) affects not only the precision but also the accuracy of quantitative metrics extracted from the images resulting in noise-induced bias. This phantom study aims to identify the radiomic features that are robust to noise in terms of precision and accuracy and to explore some methods that might help to correct noise-induced bias.

METHODS: A phantom containing three 18F-FDG filled 3D printed inserts, reflecting heterogeneous tracer uptake and realistic tumor shapes, was used in the study. The three different phantom inserts were filled and scanned with three different tumor-to-background ratios, simulating a total of nine different tumors. From the 40-minute list-mode data, ten frames each for 5 s, 10 s, 30 s, and 120 s frame duration were reconstructed to generate images with different noise levels. Under these noise conditions, the precision and accuracy of the radiomic features were analyzed using intraclass correlation coefficient (ICC) and similarity distance metric (SDM) respectively. Based on the ICC and SDM values, the radiomic features were categorized into four groups: poor, moderate, good, and excellent precision and accuracy. A “difference image” created by subtracting two statistically equivalent replicate images was used to develop a model to correct the noise-induced bias. Several regression methods (e.g., linear, exponential, sigmoid, and power-law) were tested. The best fitting model was chosen based on Akaike information criteria.

RESULTS: Several radiomic features derived from low SNR images have high repeatability, with 68% of radiomic features having ICC ≥ 0.9 for images with a frame duration of 5 s. However, most features show a systematic bias that correlates with the increase in noise level. Out of 143 features with noise-induced bias, the SDM values were improved based on a regression model (53 features to excellent and 67 to good) indicating that the noise-induced bias of these features can be, at least partially, corrected.

CONCLUSION: To have a predictive value, radiomic features should reflect tumor characteristics and be minimally affected by noise. The present study has shown that it is possible to correct for noise-induced bias, at least in a subset of the features, using a regression model based on the local image noise estimates.

PMID:36006959 | DOI:10.1371/journal.pone.0272643

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Nevin Manimala Statistics

Effectiveness of graded motor imagery protocol in phantom limb pain in amputed patient: Protocol of a randomized clinical trial

PLoS One. 2022 Aug 25;17(8):e0273356. doi: 10.1371/journal.pone.0273356. eCollection 2022.

ABSTRACT

OBJECTIVE: The aim of this study is to analyse the effectiveness of the Graded Motor Imagery (GraMI) protocol in phantom limb pain in amputee patients.

MATERIALS AND METHODS: A randomised clinical trial will be conducted, with two parallel groups and simple blinding, and a phenomenological study with semi-structured interviews. People over the age of 18, with amputation of one limb, with a minimum score of 3 on the visual analogue scale of pain, who are pharmacologically stable and have been discharged from hospital, will be recruited. An initial assessment, a post-intervention assessment (9 weeks) and a follow-up assessment (12 weeks post-intervention) will be performed, in which pain, quality of life, functionality and psychological aspects will be assessed. The aim of the qualitative study is to find out about the experience of living with phantom limb pain and to identify the satisfaction with the intervention. A descriptive, univariate and bivariate quantitative statistical analysis will be performed using the SPSS program, with a 95% confidence level and a statistical significance level of p < 0.05. The qualitative analysis will be carried out using the Atlas.ti 8.0 program, where the different interviews will be analysed, coded and categorised.

DISCUSSION: The GraMI protocol allows the patient to work on motor learning through brain reorganisation, analytical movements, sensory stimulation, and functional activities. In addition, it can help to standardise the use of graded motor imagery in future studies and in clinical practice with this patient profile.

TRIAL REGISTRATION: NCT05083611.

PMID:36006951 | DOI:10.1371/journal.pone.0273356

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A distinct four-value blood signature of pyrexia under combination therapy of malignant melanoma with dabrafenib and trametinib evidenced by an algorithm-defined pyrexia score

PLoS One. 2022 Aug 25;17(8):e0273478. doi: 10.1371/journal.pone.0273478. eCollection 2022.

ABSTRACT

Pyrexia is a frequent adverse event of BRAF/MEK-inhibitor combination therapy in patients with metastasized malignant melanoma (MM). The study’s objective was to identify laboratory changes which might correlate with the appearance of pyrexia. Initially, data of 38 MM patients treated with dabrafenib plus trametinib, of which 14 patients developed pyrexia, were analysed retrospectively. Graphical visualization of time series of laboratory values suggested that a rise in C-reactive-protein, in parallel with a fall of leukocytes and thrombocytes, were indicative of pyrexia. Additionally, statistical analysis showed a significant correlation between lactate dehydrogenase (LDH) and pyrexia. An algorithm based on these observations was designed using a deductive and heuristic approach in order to calculate a pyrexia score (PS) for each laboratory assessment in treated patients. A second independent data set of 28 MM patients, 8 with pyrexia, was used for the validation of the algorithm. PS based on the four parameters CRP, LDH, leukocyte and thrombocyte numbers, were statistically significantly higher in pyrexia patients, differentiated between groups (F = 20.8; p = <0.0001) and showed a significant predictive value for the diagnosis of pyrexia (F = 6.24; p = 0.013). We provide first evidence that pyrexia in patients treated with BRAF/MEK-blockade can be identified by an algorithm that calculates a score.

PMID:36006943 | DOI:10.1371/journal.pone.0273478

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Nevin Manimala Statistics

Antibacterial Activity of Different Extracts of Ascomata of Morchella conica and M. esculenta (Ascomycota) against Salmonella Species

Int J Med Mushrooms. 2022;24(9):85-95. doi: 10.1615/IntJMedMushrooms.2022044572.

ABSTRACT

Antibiotic resistance has become a worldwide concern, as it has reduced the clinical efficiency of multiple antibiotics. As a result, screening of novel antibacterial substances for antimicrobial potential has increased. Mushrooms are widely known as a source of antimicrobial agents. The current study was designed to investigate the bacteriostatic and bactericidal effects of Morchella conica and M. esculenta against typhoidal and nontyphoidal Salmonella species. The sensitivity of S. typhi, S. paratyphi-A, and S. typhimurium was determined using an agar diffusion assay. The standard broth microdilution method was used to assess the minimal inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Bacterial growth and inhibition kinetics were evaluated spectrophotometrically. All of the mushroom extracts were able to inhibit the growth of typhoidal and nontyphoidal Salmonella species. Notably, all of the extracts possessed bacteriostatic effects (MIC: 3.33 ± 0.6 to 16.0 ± 0 mg/mL) and bactericidal effects (MBC: 8-16 mg/mL). The results showed statistically significant differences of antibacterial and bactericidal potential of mushroom extracts against the tested bacteria (P ≤ 0.05). Thus, extracts of Morchella species can be used as natural antibacterial pharmaceuticals. Further mycopharmacological studies must be performed to characterize their metabolites.

PMID:36004712 | DOI:10.1615/IntJMedMushrooms.2022044572

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Descriptive studies and descriptive statistics

Am J Epidemiol. 2022 Aug 25:kwac152. doi: 10.1093/aje/kwac152. Online ahead of print.

NO ABSTRACT

PMID:36004704 | DOI:10.1093/aje/kwac152

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Dosimetric analysis of MR-LINAC treatment plans for salvage spine SBRT re-irradiation

J Appl Clin Med Phys. 2022 Aug 25:e13752. doi: 10.1002/acm2.13752. Online ahead of print.

ABSTRACT

PURPOSE: We investigated the feasibility of thoracic spine stereotactic body radiotherapy (SBRT) using the Elekta Unity magnetic resonance-guided linear accelerator (MRL) in patients who received prior radiotherapy. We hypothesized that Monaco treatment plans can improve the gross tumor volume minimum dose (GTVmin) with spinal cord preservation and maintain consistent plan quality during daily adaptation.

METHODS: Pinnacle clinical plans for 10 patients who underwent thoracic spine SBRT (after prior radiotherapy) were regenerated in the Monaco treatment planning system for the Elekta Unity MRL using 9 and 13 intensity-modulated radiotherapy (IMRT) beams. Monaco adapt-to-position (ATP) and adapt-to-shape (ATS) workflow plans were generated using magnetic resonance imaging with a simulated daily positional setup deviation, and these adaptive plans were compared with Monaco reference plans. Plan quality measures included target coverage, Paddick conformity index, gradient index, homogeneity index, spinal cord D0.01cc , esophagus D0.01cc , lung V10, and skin D0.01cc .

RESULTS: GTVmin values from the Monaco 9-beam and 13-beam plans were significantly higher than those from Pinnacle plans (p < 0.01) with similar spinal cord dose. Spinal cord D0.01cc , esophagus D0.01cc , and lung V10 did not statistically differ among the three plans. The electron-return effect did not induce remarkable dose effects around the lungs or skin. While in the ATP workflow, a large increase in GTVmin was observed at the cost of a 10%-50% increase in spinal cord D0.01cc , in the ATS workflow, the spinal cord dose increase was maintained within 3% of the reference plan.

CONCLUSION: These findings show that MRL plans for thoracic spine SBRT are safe and feasible, allowing tumor dose escalation with spinal cord preservation and consistent daily plan adaptation using the ATS workflow. Careful plan review of hot spots and lung dose is necessary for safe MRL-based treatment.

PMID:36004700 | DOI:10.1002/acm2.13752

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Rib cortical bone thickness variation in adults by age and sex

J Anat. 2022 Aug 25. doi: 10.1111/joa.13751. Online ahead of print.

ABSTRACT

Rib fractures are a common and serious outcome of blunt thoracic trauma and their likelihood is greater in older individuals. Osteoporotic bone loss is a well-documented aging phenomenon with sex-specific characteristics, but within rib bones, neither baseline maps of regional thickness nor the rates of bone thinning with age have been quantified across whole ribs. This study presents such data from 4014 ribs of 240 adult subjects aged 20-90. A validated cortical bone mapping technique was applied to clinical computed tomography scans to obtain local rib cortical bone thickness measurements over the surfaces of ribs 2 through 11. Regression models to age and sex gave rates of cortex thinning in local zones and aggregated across whole ribs. The statistical parametric mapping provided these relationships regionally as a function of rib surface location. All models showed significant reductions in bone thickness with age (p < 0.01). Average whole-rib thinning occurred at between 0.011 to 0.032 mm/decade (males) and 0.035 to 0.043 mm/decade (females), with sex and age accounting for up to 37% of population variability (R2 ). Rates of thinning differed regionally and by rib, with the highest bone loss of up to 0.074 mm/decade occurring in mid-rib cutaneous and superior regions of ribs 2-6. Rates were consistently higher in females than males (significantly so across whole ribs but not all local regions) and were more pronounced in cutaneous, superior, and inferior rib aspects (average 0.025 mm/decade difference in ribs 4-8) compared to pleural aspects which had the thickest cortices but saw only minor differences in thinning rates by sex (0.045 mm/decade for females and 0.040 mm/decade for males). Regional analysis showed male and female bone thickness differences that were not statistically significant at 20 years of age (p > 0.05 across practically all regions) but subsequent cortex thinning meant that substantial pleural and cutaneous regions were thinner (p < 0.05) in females than males by 55 years of age. The techniques and results from this study can be applied to assess rib bone content loss in clinical settings across wide populations. Additionally, average cortex thickness results can be mapped directly to finite element models of the thorax, and regression results are used to modify such models to represent the ribs of men and women across their full adult lifespan.

PMID:36004686 | DOI:10.1111/joa.13751

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Nevin Manimala Statistics

Opioid use disorder among Ohio’s Medicaid population: Prevalence estimates from nineteen counties using a multiplier method

Am J Epidemiol. 2022 Aug 25:kwac154. doi: 10.1093/aje/kwac154. Online ahead of print.

ABSTRACT

The decades-long overdose epidemic in the US is driven by opioid misuse. Overdoses commonly, though not exclusively, occur in individuals with opioid use disorder (OUD). To allocate adequate resources and develop appropriately scaled public health responses, accurate estimation of the prevalence of OUD is needed. Indirect methods (e.g., multiplier method) of estimating prevalence of problematic substance use behavior circumvent some limitations of household surveys and use of administrative data. We used a multiplier method to estimate OUD prevalence among the adult Medicaid population (ages 18-64) in 19 Ohio counties that are highly affected by overdose. We used Medicaid claims data and National Vital Statistics System overdose death data, which were linked at the person level. A statistical model leveraged opioid-related death rate information from a group with known OUD to estimate prevalence among a group with unknown OUD status given recorded opioid-related deaths in that group. We estimated that 13.6% of the total study population had OUD in 2019. Males (16.7%) had a higher prevalence of OUD than females (11.4%) and persons aged 35-54 had the highest prevalence (16.7%). Our approach to prevalence estimation has important implications for OUD surveillance and treatment in the United States.

PMID:36004683 | DOI:10.1093/aje/kwac154

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A latent state space model for estimating brain dynamics from electroencephalogram (EEG) data

Biometrics. 2022 Aug 25. doi: 10.1111/biom.13742. Online ahead of print.

ABSTRACT

Modern neuroimaging technologies have substantially advanced the measurement of brain activity. Electroencephalogram (EEG) as a non-invasive neuroimaging technique measures changes in electrical voltage on the scalp induced by brain cortical activity. With its high temporal resolution, EEG has emerged as an increasingly useful tool to study brain connectivity. Challenges with modeling EEG signals of complex brain activity include interactions among unknown sources, low signal-to-noise ratio and substantial between-subject heterogeneity. In this work, we propose a state space model that jointly analyzes multi-channel EEG signals and learns dynamics of different sources corresponding to brain cortical activity. Our model borrows strength from spatially correlated measurements and uses low-dimensional latent states to explain all observed channels. The model can account for patient heterogeneity and quantify the effect of a subject’s covariates on the latent space. The EM algorithm, Kalman filtering, and bootstrap resampling are used to fit the state space model and provide comparisons between patient diagnostic groups. We apply the developed approach to a case-control study of alcoholism and reveal significant attenuation of brain activity in response to visual stimuli in alcoholic subjects compared to healthy controls. This article is protected by copyright. All rights reserved.

PMID:36004670 | DOI:10.1111/biom.13742

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Understanding the effects of a complex psychological intervention on symptoms of depression in Goa, India: findings from a causal mediation analysis

Br J Psychiatry. 2022 Aug 25:1-7. doi: 10.1192/bjp.2022.116. Online ahead of print.

ABSTRACT

BACKGROUND: Understanding how and under what circumstances a highly effective psychological intervention, improved symptoms of depression is important to maximise its clinical effectiveness.

AIMS: To address this complexity, we estimate the indirect effects of potentially important mediators to improve symptoms of depression (measured with the Patient Health Questionnaire (PHQ-9)) in the Healthy Activity Program trial.

METHOD: Interventional in(direct) effects were used to decompose the total effect of the intervention on PHQ-9 scores into the direct and indirect effects. The following indirect effects were considered: characteristics of sessions, represented by the number of sessions and homework completed; behavioural activation, according to an adapted version of the Behavioural Activation for Depression Scale – Short Form; and extra sessions offered to participants who did not respond to the intervention.

RESULTS: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.1, bias-corrected 95% CI -3.2 to -1.5), 34% was mediated through improved levels of behavioural activation (mean difference: -0.7, bias-corrected 95% CI -1.2 to -0.4). There was no evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment.

CONCLUSIONS: Findings from our robust mediation analyses confirmed the importance of targeting behavioural activation. Contrary to published literature, our findings suggest that neither the number of sessions nor proportion of homework completed improved outcomes. Moreover, in this context, alternative treatments other than extra sessions should be considered for patients who do not respond to the intervention.

PMID:36004665 | DOI:10.1192/bjp.2022.116