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Nevin Manimala Statistics

Policy impacts of statistical uncertainty and privacy

Science. 2022 Aug 26;377(6609):928-931. doi: 10.1126/science.abq4481. Epub 2022 Aug 25.

ABSTRACT

Funding formula reform may help address unequal impacts of uncertainty from data error and privacy protections.

PMID:36007047 | DOI:10.1126/science.abq4481

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Nevin Manimala Statistics

Reference rate for post-tonsillectomy haemorrhage in Australia-A 2000-2020 national hospital morbidity database analysis

PLoS One. 2022 Aug 25;17(8):e0273320. doi: 10.1371/journal.pone.0273320. eCollection 2022.

ABSTRACT

This study aims to provide a national benchmark rate of post-tonsillectomy haemorrhage (PTH) in Australia. Using data from Australia’s National Hospital Morbidity Database (NHMD) from 1 July 2000 to 30 June 2020, we have conducted a nation-wide population-based study to estimate a reference rate of PTH. Outcomes of interest included the overall rate and time-trend of PTH, the relationship between PTH rates with age and gender as well as the epidemiology of tonsillectomy procedures. A total of 941,557 tonsillectomy procedures and 15,391 PTH episodes were recorded for the study period. Whilst the incidence of tonsillectomy procedures and the number of day-stay tonsillectomy procedures have increased substantially over time, the overall rate of PTH for all ages has remained relatively constant (1.6% [95% CI: 1.61 to 1.66]) with no significant association observed between the annual rates of PTH and time (year) (Spearman correlation coefficient, Rs = 0.24 (95% CI: -0.22 to 0.61), P = 0.3). However, the rate of PTH in adults (aged 15 years and over) experienced a statistically significant mild to moderate upward association with time (year) Rs = 0.64 (95% CI: 0.28 to 0.84), P = 0.003. Analysis of the odds of PTH using the risk factors of increasing age and male gender showed a unique age and gender risk pattern for PTH where males aged 20 to 24 years had the highest risk of PTH odds ratio 7.3 (95% CI: 6.7 to 7.8) compared to patients aged 1 to 4 years. Clinicians should be mindful of the greater risk of PTH in male adolescents and young adults. The NHMD datasets can be continually used to evaluate the benchmark PTH rate in Australia and to facilitate tonsillectomy surgical audit activities and quality improvement programs on a national basis.

PMID:36006990 | DOI:10.1371/journal.pone.0273320

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Nevin Manimala Statistics

Quantitative bile and serum proteomics for the screening and differential diagnosis of primary sclerosing cholangitis

PLoS One. 2022 Aug 25;17(8):e0272810. doi: 10.1371/journal.pone.0272810. eCollection 2022.

ABSTRACT

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary strictures, cholestasis, and a markedly increased risk of cholangiocarcinoma. New markers for the screening and differential diagnosis of PSC are needed. In this pilot study, we have analyzed both the bile and serum proteomic profiles of 80 PSC patients and non-PSC controls (n = 6 for bile and n = 18 for serum).

AIM: The aim of this study was to discover candidates for new biomarkers for the differential diagnosis of PSC.

METHODS: Bile and serum samples were processed and subsequently analyzed using ultra performance liquid chromatography-ultra definition mass spectrometry (UPLC-UDMSE). Further analysis included statistical analyses such as receiver operating characteristic curve analysis as well as pathway analysis using Ingenuity Pathway Analysis.

RESULTS AND CONCLUSIONS: In bile, we discovered 64 proteins with significantly different levels between the groups, with fold changes of up to 129. In serum, we discovered 112 proteins with significantly different levels. Receiver operating characteristic curve analysis found multiple proteins with high area under the curve values, up to 0.942, indicating that these serum proteins are of value as new non-invasive classifiers of PSC. Pathway analysis revealed multiple canonical pathways that were enriched in the dataset, which have roles in bile homeostasis and metabolism. We present several serum proteins that could serve as new blood-based markers for the diagnosis of PSC after further validation. The measurement of serum levels of these proteins could be of use in the screening of patients with suspected PSC.

PMID:36006970 | DOI:10.1371/journal.pone.0272810

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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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Nevin Manimala Statistics

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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Nevin Manimala Statistics

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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Nevin Manimala Statistics

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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Nevin Manimala Statistics

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