Nevin Manimala

Phys Med Biol. 2022 Mar 21. doi: 10.1088/1361-6560/ac5f73. Online ahead of print.

ABSTRACT

OBJECTIVE: Data-driven gating (DDG) can address patient motion issues and enhance PET quantification but suffers from increased image noise from utilization of <100% of PET data. Misregistration between DDG-PET and CT may also occur, altering the potential benefits of gating. Here, the effects of PET acquisition time and CT misregistration were assessed with a combined DDG-PET/DDG-CT technique.

APPROACH: In the primary PET bed with lesions of interest and likely respiratory motion effects, PET acquisition time was extended to 12 min and a low-dose cine CT was acquired to enable DDG-CT. Retrospective reconstructions were created for both non-gated (NG) and DDG-PET using 30 sec to 12 min of PET data. Both the standard helical CT and DDG-CT were used for attenuation correction of DDG-PET data. SUVmax, SUVpeak, and CNR were compared for 45 lesions in the liver and lung from 27 cases.

MAIN RESULTS: For both NG-PET (p=0.0041) and DDG-PET (p=0.0028), only the 30 sec acquisition time showed clear SUVmax bias relative to the 3 min clinical standard. SUVpeak showed no bias at any change in acquisition time. DDG-PET alone increased SUVmax by 15±20% (p<0.0001), then was increased further by an additional 15±29% (p=0.0007) with DDG-PET/CT. Both 3 min and 6 min DDG-PET had lesion CNR statistically equivalent to 3 min NG-PET, but then increased at 12 min by 28±48% (p=0.0022). DDG-PET/CT at 6 min had comparable counts to 3 min NG-PET, but significantly increased CNR by 39±46% (p<0.0001).

SIGNIFICANCE: 50% counts DDG-PET did not lead to inaccurate or biased SUV – increased SUV resulted from gating. Improved registration from DDG-CT was equally as important as motion correction with DDG-PET for increasing SUV in DDG-PET/CT. Lesion detectability could be significantly improved when DDG-PET used equivalent counts to NG-PET, but only when combined with DDG-CT in DDG-PET/CT.

PMID:35313286 | DOI:10.1088/1361-6560/ac5f73

Int Immunopharmacol. 2022 Mar 17;107:108689. doi: 10.1016/j.intimp.2022.108689. Online ahead of print.

ABSTRACT

OBJECTIVES: This study was designed to compare the efficacy and safety of methylprednisolone and tocilizumab in the treatment of patients with severe COVID-19.

METHODS: During a prospective cohort study, hospitalized patients with severe COVID-19 received intravenous methylprednisolone (250-500 mg daily up to three doses), weight-based tocilizumab (maximum 800 mg, one or two doses as daily interval) or dexamethasone (8 mg daily). The primary outcome was time to onset of clinical response. Secondary outcomes were improvement rate of oxygen saturation and CRP, need for ICU admission, duration of hospitalization and 28-day mortality. During study, adverse events of the treatments were recorded.

RESULTS: Although the difference was not statistically significant (p = 0.090), clinical response occurred faster in the tocilizumab group than other groups (10 vs. 16 days). Clinical response was detected in 74.19%, 81.25%, and 60% of patients in the methylprednisolone, tocilizumab, and dexamethasone groups respectively (p = 0.238). Based on the Cox regression analysis and considering dexamethasone as the reference group, HR (95% CI) of clinical response was 1.08 (0.65-1.79) and 1.46 (0.89-2.39) in the methylprednisolone and tocilizumab groups respectively. Improvement rate of oxygen saturation and CRP was not significantly different between the groups (p = 0.791 and p = 0.372 respectively). Also need for ICU admission and 28-day mortality was comparable between the groups (p = 0.176 and p = 0.143 respectively). Compared with methylprednisolone, tocilizumab caused more sleep disturbances (p = 0.019). Other adverse events were comparable among patients in the groups.

CONCLUSION: When or where access to tocilizumab is a problem, methylprednisolone may be considered as an alternative for the treatment of patients with severe COVID-19.

PMID:35313272 | DOI:10.1016/j.intimp.2022.108689

Appl Radiat Isot. 2022 Mar 16;184:110198. doi: 10.1016/j.apradiso.2022.110198. Online ahead of print.

ABSTRACT

Periodic intermediate checks on the equipment used for calibration activity accredited for the conformity with the international norm ISO/IEC 17025 are an essential issue for monitoring the validity of calibration laboratory’s results. These checks should be carried out according to a procedure defined by each accredited laboratory. The results of these checks should not exceed the acceptance criteria established in the laboratory and statistical techniques shall be applied to the reviewing of the results. In this work, a simple method of carrying out intermediate checks on working standards used for calibrations of ionizing radiation dosimeters in a ⁶⁰Co gamma ray beam was presented. Moreover, the statistical analysis of obtained results was presented. This analysis allowed for a reliable inference regarding the operation of the working standards used to calibrate the customer’s devices. The presented methods can be used as a guidance in order to conform to the ISO/IEC 17025 requirements for carrying out and reviewing of periodic intermediate checks results in the area of calibrations of ionizing radiation dosimeters for external beam radiotherapy.

PMID:35313266 | DOI:10.1016/j.apradiso.2022.110198

Psychoneuroendocrinology. 2022 Mar 9;139:105717. doi: 10.1016/j.psyneuen.2022.105717. Online ahead of print.

ABSTRACT

Adverse childhood experiences (ACEs) have been associated with unfavorable health outcomes throughout the life up to old age. Mechanisms through which ACEs impact later life health are still not entirely clear. There is growing evidence for the idea that alterations in the hypothalamic pituitary adrenal (HPA) axis might cause the effects of ACEs on later health consequences. Only few studies have investigated associations between ACEs and diurnal HPA axis functioning in older adults. Therefore, we investigated the impact of type and timing of ACEs linked to flight of war on diurnal HPA axis activity in a sample of East Prussian World War II refugees aged 74-91 years. We calculated a dichotomous variable according to the (minimum) age at trauma: early ACE (eACE; 0-5 years) and late ACE (lACE; 6-17 years). Multiple linear regression analysis using different ACEs linked to flight of war (war-related trauma, individual experience of violence, neglect) as well as age at trauma and the interactions of ACEs and age at trauma as predictors and three cortisol outcomes (AUC_G (area under the curve with respect to the ground), decline (morning to night) and CAR (cortisol awakening response)) was performed. For AUC_G, we found a negative association of individual experience of violence only in lACE participants. For decline, a positive association with neglect was observed for the whole study sample. The overall model for CAR was not statistically significant. Our findings support the hypothesis that type as well as timing of ACEs might influence diurnal HPA axis functioning into old age. These findings may contribute to a better understanding of the lifelong influence of ACEs.

PMID:35313255 | DOI:10.1016/j.psyneuen.2022.105717

Knee. 2022 Mar 18;35:149-156. doi: 10.1016/j.knee.2022.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Ten-segment classification provides a different approach to the evaluation of tibial plateau fractures. The purpose of this study was to assess the intra- and inter-observer reliability of three widely used classification systems (Schatzker, Arbeitsgemeinschaft für Osteosynthesefragen (AO/OTA), and the updated three-column concept (uTCC)) with ten-segment classification in two-dimensional computed tomography (2D-CT) and three-dimensional computed tomography (3D-CT).

METHOD: Ninety 2D-CT and 3D-CT scans of patients with tibial plateau fractures were included in this retrospective cohort study. The included data were independently classified by six observers of different years of seniority and were independently observed and classified again after eight weeks. Inter-observer and intra-observer reliability of the four fracture classifications made by the six observers was analyzed using the kappa statistic. Kappa values were interpreted according to the categorical rating by Landis and Koch.

RESULTS: When the inter-observer reliability was based on 2D-CT/3D-CT analysis, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.64/0.66, 0.56/0.59, 0.53/0.65, and 0.60/0.73, respectively. When intra-observer reliability was based on 2D-CT/3D-CT, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.68/0.83, 0.69/0.83, 0.74/0.85, and 0.80/0.91, respectively.

CONCLUSIONS: The use of 3D-CT is important for the reliable diagnosis and recognition of tibial plateau fracture features compared to 2D-CT. When using 3D-CT, ten-segment classification showed high intra- and inter-observer agreement.

PMID:35313243 | DOI:10.1016/j.knee.2022.03.002

Am J Emerg Med. 2022 Mar 4;55:126-132. doi: 10.1016/j.ajem.2022.02.046. Online ahead of print.

ABSTRACT

OBJECTIVE: Sodium valproate and ibuprofen are drugs with known efficacy in the treatment of headache associated with acute migraine attacks. In this study, our aim was to compare the efficacy of these two drugs in the treatment of acute migraine attacks when administered as a single intravenous (IV) dose in the emergency department.

MATERIALS AND METHOD: This study was designed as a prospective, randomized controlled, double-blinded study and included patients aged 18 to 65 years who presented to the emergency department with acute headache and met the criteria of ‘migraine without aura’ according to the International Classification of Headache Disorders. The patients were randomized into two groups and given a single dose of 800 mg sodium valproate or 800 mg ibuprofen in 150 mL of normal saline by IV infusion over five minutes. Changes in pain levels were assessed using the Numerical Rating Scale (NRS) for pain over a two-hour period.

RESULTS: Ninety-nine patients (49 patients in the sodium valproate group and 50 in the ibuprofen group) completed the trial, and their data were included in the statistical analysis. The mean decrease in the post-treatment delta NRS values was statistically significantly higher in the sodium valproate group than in the ibuprofen group. The mean differences were 1.69 [confidence interval (CI): 1.02-2.37, p<0.001], the mean difference between N0 and N2 was 3.61 (CI: 2.96-4.26, p < 0.001), the mean difference between N0 and N3 was 4.11 (CI: 3.54-4.67, p < 0.001), and the mean difference between N0 and N4 was 3.92 (CI: 3.67-4.46, p < 0.001). The number of patients who achieved the primary endpoint of pain relief was significantly higher in the sodium valproate group than in the ibuprofen group (p < 0.001). According to the Kaplan-Meier analysis showing the rates of reaching the targeted endpoint, there was a significant difference in the efficacy of the two-treatment group (χ2 = 79.98, CI: 80.35-99.65; p = 0.000).

PMID:35313227 | DOI:10.1016/j.ajem.2022.02.046

Forensic Sci Int Genet. 2022 Mar 9;58:102680. doi: 10.1016/j.fsigen.2022.102680. Online ahead of print.

ABSTRACT

The Hardy-Weinberg law is shown to be transitive in the sense that a multi-allelic polymorphism that is in equilibrium will retain its equilibrium status if any allele together with its corresponding genotypes is deleted from the population. Similarly, the transitivity principle also applies if alleles are joined, which leads to the summation of allele frequencies and their corresponding genotype frequencies. These basic polymorphism properties are intuitive, but they have apparently not been formalized or investigated. This article provides a straightforward proof of the transitivity principle, and its usefulness in genetic data analysis is explored, using high-quality autosomal microsatellite databases from the US National Institute of Standards and Technology. We address the reduction of multi-allelic polymorphisms to variants with fewer alleles, two in the limit. Equilibrium test results obtained with the original and reduced polymorphisms are generally observed to be coherent, in particular when results obtained with length-based and sequence-based microsatellites are compared. We exploit the transitivity principle in order to identify disequilibrium-related alleles, and show its usefulness for detecting population substructure and genotyping problems that relate to null alleles and allele imbalance.

PMID:35313226 | DOI:10.1016/j.fsigen.2022.102680

Stud Hist Philos Sci. 2022 Mar 18;93:39-46. doi: 10.1016/j.shpsa.2021.12.012. Online ahead of print.

ABSTRACT

Two things about Gregor Mendel are common knowledge: first, that he was the “monk in the garden” whose experiments with peas in mid-nineteenth-century Moravia became the starting point for genetics; second, that, despite that exalted status, there is something fishy, maybe even fraudulent, about the data that Mendel reported. Although the notion that Mendel’s numbers were, in statistical terms, too good to be true was well understood almost immediately after the famous “rediscovery” of his work in 1900, the problem became widely discussed and agonized over only from the 1960s, for reasons having as much to do with Cold War geopolitics as with traditional concerns about the objectivity of science. Appreciating the historical origins of the problem as we have inherited it can be a helpful step in shifting the discussion in more productive directions, scientific as well as historiographic.

PMID:35313209 | DOI:10.1016/j.shpsa.2021.12.012

Eur J Cancer. 2022 Mar 18;166:219-228. doi: 10.1016/j.ejca.2022.01.031. Online ahead of print.

ABSTRACT

AIM: The APHINITY trial showed that adding adjuvant pertuzumab (P) to trastuzumab and chemotherapy, compared with adding placebo (Pla), significantly improved invasive disease-free survival (IDFS) for patients with HER2+ early breast cancer both overall and for the node-positive (N+) cohort. We explored whether adding P could benefit some N- subpopulations and whether to consider de-escalation for some N+ subpopulations.

METHODS: Subpopulation Treatment Effect Pattern Plot (STEPP) is an exploratory, graphical method that plots estimates of treatment effect for overlapping patient subpopulations defined by a covariate of interest. We used STEPP to estimate Kaplan-Meier differences in 6-year IDFS percentages (P minus Pla: Δ ± standard error [SE]), both overall and by nodal status, for overlapping subpopulations defined by (1) a clinical composite risk score, (2) tumour infiltrating lymphocytes (TILs) percentage, and (3) human epidermal growth factor receptor 2 (HER2) FISH copy number. Because of multiplicity, a Δ of at least three SE is required to warrant attention.

RESULTS: The average absolute gains in 6-year IDFS percentages were 2.8 ± 0.9 overall; 4.5 ± 1.2 for N+ and 0.1 ± 1.1 for N-. Largest gains were for patients with intermediate clinical composite risk (5.3 ± 1.9 overall; 6.9 ± 2.3 N+; 4.0 ± 3.0 N-), highest TILs percentage (6.3 ± 1.7 overall; 7.4 ± 2.4 N+; 3.2 ± 1.7 N-), and intermediate HER2 copy number (2.8 ± 1.9 overall; 7.4 ± 2.5 N+; -1.3 ± 1.9 N-), but clear evidence indicating a pattern of differential subpopulation treatment effects was lacking.

CONCLUSIONS: STEPP plots for N- did not identify subpopulations clearly benefiting from adding P, and those for N+ did not identify subpopulations warranting de-escalation. TILs percentage appeared to be more predictive of P treatment effect than clinical composite risk score.

TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01358877.

PMID:35313167 | DOI:10.1016/j.ejca.2022.01.031

Value Health Reg Issues. 2022 Mar 18;31:1-9. doi: 10.1016/j.vhri.2022.02.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Estimation of the lost productivity cost of premature deaths because of cancers can provide invaluable information for identifying the priorities and resource needs in the design of cancer control strategies. This study aimed to estimate the premature mortality costs because of cancers using GLOBOCAN estimates in Iran.

METHODS: In this study, we estimated the lost productivity cost of premature deaths because of cancers in Iran from 2012 and 2018, using the human capital approach with respect to the cancer site, sex, and age. Data on cancer mortality were extracted from the GLOBOCAN reports. In addition, economic information, such as annual income, employment rate, housekeeping rate, and gross domestic product, was extracted from the World Bank Data and the Statistical Center of Iran. A discount rate of 3% was applied and costs were reported in constant 2017 international dollars.

RESULTS: From 2012 and 2018, the lost productivity cost of premature deaths because of cancers increased by 18% in Iran ($2453 million in 2012 and $2887 million in 2018). In contrast, the number of deaths and the years of life lost because of cancers increased by approximately 8%. The mortality cost was approximately 35% and 56% higher in men than in women in 2012 and 2018, respectively. Stomach, colorectal, esophageal, and breast cancers accounted for > 40% of total cancer mortality costs in 2012. Stomach cancer, brain cancer, nervous system cancer, lung cancer, and leukemia were responsible for 57% of cancer mortality costs in 2018.

CONCLUSIONS: Based on the findings, the lost productivity costs of premature mortality because of cancers have increased significantly in Iran. Overall, evidence-based policy making for managing the costs of cancers and resource allocation depends on analyzing epidemiological and economic data in the health sector. This study presented helpful findings on cancer mortality costs to support evidence for decision making in healthcare systems.

PMID:35313156 | DOI:10.1016/j.vhri.2022.02.002