Tag: statistics

Phys Med Biol. 2024 Feb 21. doi: 10.1088/1361-6560/ad2b97. Online ahead of print.

ABSTRACT

Objective: Proton therapy currently faces challenges from clinical complications on organs-at-risk due to range uncertainties, anatomical changes, and setup errors. To address this issue, Positron Emission Tomography (PET) of the proton-induced¹¹C and¹⁵O activity has been used to provide feedback on the proton range. However, this approach is not instantaneous due to the long half-lives of these nuclides. An alternative nuclide,¹²N (half-life 11 ms), shows promise for real-time in vivo verification of the proton range. Development of¹²N imaging requires better knowledge of its production reaction cross section.
Approach: The¹²C(p,n)¹²N reaction cross section was measured by detecting positron activity of graphite targets irradiated with 66.5, 120, and 150 MeV protons. A pulsed beam delivery with 0.7-2×10⁸protons per pulse was used. The positron activity was measured during the beam-off periods using a dual-head Siemens Biograph mCT PET scanner. The¹²N production was determined from activity time histograms.
Main results: The cross section was calculated for 11 energies, ranging from 23.5 to 147 MeV, using information on the experimental setup and beam delivery. Through a comprehensive uncertainty propagation analysis, a statistical uncertainty of 2.6-5.8% and a systematic uncertainty of 3.3-4.6% were achieved. Additionally, calibration measurements showed a systematic correction factor of 1.21 (± 7.5%), which contributed the most to global uncertainty. Despite this, there was an improvement in the precision of the cross section measurement compared to values reported by the only previous study for this nuclear reaction. To obtain a continuous cross section function, a weighted spline interpolation using both datasets was performed.
Significance: Our results were incorporated into the RayStation Monte Carlo (MC) engine for calculating the¹²N positron annihilation distribution during treatment, with the aim of developing an MC simulation framework to predict¹²N PET imaging for range verification purposes.

PMID:38382103 | DOI:10.1088/1361-6560/ad2b97

Global Spine J. 2024 Feb 21:21925682241235605. doi: 10.1177/21925682241235605. Online ahead of print.

ABSTRACT

STUDY DESIGN: Metanalysis.

OBJECTIVE: Surgical site infections (SSI) is one of the commonest postoperative adverse events after spine surgery. Frailty has been described as a valuable summary risk indicator for SSI in spine surgery. The aim of this metanalysis is to evaluate the influence of frailty on postoperative SSI in this cohort and provide hints on which index can predict the risk of SSI.

METHODS: Papers describing the postoperative SSI rate in adult degenerative spine disease or adult spine deformity patients with varying degrees of frailty were included in the analysis. The SSI rate in different grades of frailty was considered for outcome measure. Meta-analysis was performed on studies in whom data regarding patients with different levels of frailty and occurrence of postoperative SSI could be pooled. P < .05 was considered significant.

RESULTS: 16 studies were included. The frailty prevalence measured using mFI-11 ranged from 3% to 17.9%, these values were inferior to those measured with mFI-5. Significant difference was found between frail and non-frail patients in postoperative SSI rate at metanalysis (z = 5.9547, P < .0001 for mFI-5 and z = 3.8334, P = .0001 for mFI-11).

CONCLUSION: This is the first meta-analysis to specifically investigate the impact of frailty, on occurrence of SSI. We found a relevant statistical difference between frail and non-frail patients in SSI occurrence rate. This is a relevant finding, as the ageing of population increases alongside with spine surgery procedures, a better understanding of risk factors may advance our ability to treat patients while minimizing the occurrence of SSI.

PMID:38382093 | DOI:10.1177/21925682241235605

J Phys Chem A. 2024 Feb 21. doi: 10.1021/acs.jpca.3c07437. Online ahead of print.

ABSTRACT

Luminescent organic semiconducting doublet-spin radicals are unique and emergent optical materials because their fluorescent quantum yields (Φ_fl) are not compromised by the spin-flipping intersystem crossing (ISC) into a dark high-spin state. The multiconfigurational nature of these radicals challenges their electronic structure calculations in the framework of single-reference density functional theory (DFT) and introduces room for method improvement. In the present study, we extended our earlier development of ML-ωPBE [J. Phys. Chem. Lett., 2021, 12, 9516-9524], a range-separated hybrid (RSH) exchange-correlation (XC) functional constructed using the stacked ensemble machine learning (SEML) algorithm, from closed-shell organic semiconducting molecules to doublet-spin organic semiconducting radicals. We assessed its performance for a new test set of 64 doublet-spin radicals from five categories while placing all previously compiled 3926 closed-shell molecules in the new training set. Interestingly, ML-ωPBE agrees with the nonempirical OT-ωPBE functional regarding the prediction of the molecule-dependent range-separation parameter (ω), with a small mean absolute error (MAE) of 0.0197 a₀^-1, but saves the computational cost by 2.46 orders of magnitude. This result demonstrates an outstanding domain adaptation capacity of ML-ωPBE for diverse organic semiconducting species. To further assess the predictive power of ML-ωPBE in experimental observables, we also applied it to evaluate absorption and fluorescence energies (E_abs and E_fl) using linear-response time-dependent DFT (TDDFT), and we compared its behavior with nine popular XC functionals. For most radicals, ML-ωPBE reproduces experimental measurements of E_abs and E_fl with small MAEs of 0.299 and 0.254 eV, only marginally different from those of OT-ωPBE. Our work illustrates a successful extension of the SEML framework from closed-shell molecules to doublet-spin radicals and will open the venue for calculating optical properties for organic semiconductors using single-reference TDDFT.

PMID:38382058 | DOI:10.1021/acs.jpca.3c07437

Appl Physiol Nutr Metab. 2024 Feb 21. doi: 10.1139/apnm-2023-0095. Online ahead of print.

ABSTRACT

This study examined whether Indigenous people could achieve the Canadian Physical Activity Guidelines (CPAG) recommendations for adults while engaging in the cultural practice of hunting. It was hypothesized that Indigenous hunters would achieve or surpass the physical activity thresholds set forth by the CPAG on days spent hunting. Step count and heart rate were recorded from six male participants during mule deer hunts and days spent on-reserve. Step count was not statistically different between days spent hunting (28803 ± 10657 steps) and on-reserve (15086 ± 7536 steps) (p = 0.10). The duration of sedentary activity was not statistically different between days spent hunting (531 ± 188 minutes) versus on-reserve (455 ± 117 minutes) (p = 0.34). Low (63 ± 38; 70 ± 65 minutes) (p = 0.86), moderate (32 ± 31; 22 ± 22 minutes) (p = 0.67) and vigorous (24 ± 29; 5 ± 6 minutes) intensity physical activity duration was not statistically different between hunting and on-reserve days. On hunting days, duration of moderate-to-vigorous physical activity (55 ± 58 minutes) exceeded CPAG. Trends in the data suggest that hunting is likely a viable mode of physical activity for Indigenous adults to achieve health benefits, and future studies should evaluate multiple communities to achieve a larger sample size to facilitate academic statistical methodology. However, physical activity measurements suggest that health researchers’ and clinicians should consider traditional activities such as hunting as a means for Indigenous adults to increase participation in sufficiently vigorous physical activity to incur health benefits.

PMID:38382052 | DOI:10.1139/apnm-2023-0095

J Urol. 2024 Feb 21:101097JU0000000000003884. doi: 10.1097/JU.0000000000003884. Online ahead of print.

ABSTRACT

PURPOSE: To assess the safety and efficacy of gabapentin in reducing post-operative pain among patients undergoing scrotal surgery for male infertility by conducting a randomized, double-blind, placebo-controlled trial.

MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, healthy men undergoing scrotal surgery with a single surgeon were randomized to receive either (1) gabapentin, 600 mg, given 2 hours pre-operatively and 300 mg, taken 3 times a day post-operatively for 3 days, or (2) inactive placebo. The primary outcome measure was difference in post-operative pain scores. Secondary outcomes included differences in opioid usage, patient satisfaction, and adverse events.

RESULTS: Of 97 patients screened, 74 enrolled and underwent randomization. Of these, 4 men were lost to follow-up, and 70 were included in the final analysis (35 gabapentin, 35 placebo). Both differences in initial postoperative mean pain score (-1.14, 95% CI -2.21 to -0.08, P = .035) and final mean pain scores differences (-1.27, 95% CI -2.23 to -0.32, P = .0097) indicated lower gabapentin pain compared to placebo. There were no statistically significant differences in opioid usage, patient satisfaction, or adverse events.

CONCLUSIONS: These data suggest that perioperative gabapentin results in a statistically and clinically significant decrease in pain following scrotal surgery. While there was no evidence of an impact on opioid usage or patient satisfaction, given the low risk of adverse events, it may be considered as part of a multimodal pain management strategy.

PMID:38382042 | DOI:10.1097/JU.0000000000003884

Neurology. 2024 Mar 12;102(5):e209162. doi: 10.1212/WNL.0000000000209162. Epub 2024 Feb 21.

ABSTRACT

BACKGROUND AND OBJECTIVES: Fine particulate matter (PM_2.5) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The APOE gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM_2.5 and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM_2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort.

METHODS: A cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC) score. Traffic-related PM_2.5 concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250 m. One-year, 3-year, and 5-year average PM_2.5 concentrations before death were matched to participants’ home address. We assessed the association between traffic-related PM_2.5 and AD hallmark pathology and effect modification by APOE genotype, using adjusted ordinal logistic regression models.

RESULTS: Among the 224 participants, the mean age of death was 76 years, and 57% had at least 1 APOE ε4 copy. Traffic-related PM_2.5 was significantly associated with the CERAD score for the 1-year exposure window (odds ratio [OR] 1.92; 95% CI 1.12-3.30) and the 3-year exposure window (OR 1.87; 95% CI 1.01-3.17). PM_2.5 was also associated with higher Braak stage and ABC score albeit nonsignificantly. The strongest associations between PM_2.5 and neuropathology markers were among those without APOE ε4 alleles (e.g., for the CERAD score and 1-year exposure window, OR 2.31; 95% CI 1.36-3.94), though interaction between PM_2.5 and APOE genotype was not statistically significant.

DISCUSSION: Our study found traffic-related PM_2.5 exposure was associated with the CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM_2.5 affects β-amyloid deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this association.

PMID:38382009 | DOI:10.1212/WNL.0000000000209162

Neurology. 2024 Mar 12;102(5):e209148. doi: 10.1212/WNL.0000000000209148. Epub 2024 Feb 21.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients with cerebral small vessel disease (SVD) show a heterogenous clinical course. The aim of the current study was to investigate the longitudinal course of cognitive and motor function in patients who developed parkinsonism, dementia, both, or none.

METHODS: Participants were from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study, a prospective cohort of patients with SVD. Parkinsonism and dementia were, respectively, diagnosed according to the UK Parkinson’s Disease Society brain bank criteria and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for major neurocognitive disorder. Linear and generalized linear mixed-effect analyses were used to study the longitudinal course of motor and cognitive tasks.

RESULTS: After a median follow-up of 12.8 years (interquartile range 10.2-15.3), 132 of 501 (26.3%) participants developed parkinsonism, dementia, or both. Years before diagnosis of these disorders, participants showed distinct clinical trajectories from those who developed none: Participant who developed parkinsonism had an annual percentage of 22% (95% CI 18%-27%) increase in motor part of the Unified Parkinson’s Disease Rating Scale score. This was significantly higher than the 16% (95% CI 14%-18%) of controls, mainly because of a steep increase in bradykinesia and posture and gait disturbances. When they developed dementia as well, the increase in Timed Up and Go Test time of 0.73 seconds per year (95% CI 0.58-0.87) was significantly higher than the 0.20 seconds per year increase (95% CI 0.16-0.23) of controls. All groups, including the participants who developed parkinsonism without dementia, showed a faster decline in executive function compared with controls: Annual decline in Z-score was -0.07 (95% CI -0.10 to -0.05), -0.09 (95% CI -0.11 to -0.08), and -0.11 (95% CI -0.14 to -0.08) for participants who developed, respectively, parkinsonism, dementia, and both parkinsonism and dementia. These declines were all significantly faster than the annual decline in Z-score of 0.07 (95% CI -0.10 to -0.05) of controls.

DISCUSSION: A distinct pattern in deterioration of clinical markers is visible in patients with SVD, years before the diagnosis of parkinsonism and dementia. This knowledge aids early identification of patients with a high risk of developing these disorders.

PMID:38382000 | DOI:10.1212/WNL.0000000000209148

Int J Prosthodont. 2024 Feb 21;37(7):1-7. doi: 10.11607/ijp.8376.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the mechanical properties of acrylic resins at different aging times for denture bases manufactured using the conventional method, microwave processing, milling, and 3D printing.

MATERIALS AND METHODS: A total of 160 rectangular samples (64 Å~ 10 Å~ 3.3 ± 0.03 mm) were prepared, divided among the four main resin groups, and subdivided into four analysis times (T0, T1, T2, and T3), resulting in 10 samples per subgroup. The samples were stored in distilled water at 37° ± 2°C for 24 hours (T0), then subjected to thermocycling at temperatures of 5° ± 1°C and 55° ± 1°C in different numbers of cycles: 5,000 (T1); 10,000 (T2); and 20,000 (T3). The mechanical properties evaluated were surface microhardness, flexural strength, and modulus of elasticity. Statistical differences between resin groups and aging time were evaluated using two-way analysis of variance (P < .05).

RESULTS: The 3D-printed resin showed the significantly lowest values of microhardness, flexural strength, and modulus of elasticity compared to other resins (P < .001).

CONCLUSIONS: The CAD/CAM-milled denture resin showed mechanical properties similar to those of traditional resins (conventional and microwave-processed). The 3D-printing resin did not show adequate mechanical properties for long-term clinical use. Despite this, new studies are developing better properties of this resin for long-term use.

PMID:38381998 | DOI:10.11607/ijp.8376

JCO Oncol Pract. 2024 Feb 21:OP2300591. doi: 10.1200/OP.23.00591. Online ahead of print.

ABSTRACT

PURPOSE: To examine the relationship between guideline-concordant care (GCC) on the basis of national clinical practice guidelines and survival in children (0-14 years), adolescents and young adults (AYAs, 15-39 years), and adults (40 years and older) with osteosarcoma, and to identify sociodemographic and clinical factors associated with receipt of GCC and survival.

METHODS: We used data from the California Cancer Registry (CCR) on patients diagnosed with osteosarcoma during 2004-2019, with detailed treatment information extracted from the CCR text fields, including chemotherapy regimens. Multivariable logistic and Cox proportional hazard regression were used for statistical analyses.

RESULTS: Of 1,716 patients, only 47% received GCC, with variation by age at diagnosis: 67% of children, 43% of AYAs, and 30% of adults. In multivariable models, patients who received part or all care (v none) at specialized cancer centers were more likely to receive GCC. AYAs and adults were less likely to receive GCC than children (odds ratio [OR], 0.38 [95% CI, 0.30 to 0.50] and OR, 0.40 [95% CI, 0.28 to 0.56], respectively). In a model excluding adults, patients treated by pediatric (v medical) oncologists were more likely to receive GCC (OR, 3.44 [95% CI, 2.40 to 4.94]). Patients with metastatic osteosarcoma at diagnosis who did not receive GCC had a greater hazard of death (hazard ratio [HR], 2.02 [95% CI, 1.55 to 2.63]) but no statistical differences were found in those diagnosed at earlier stages (HR, 1.15 [95% CI, 0.92 to 1.43]).

CONCLUSION: GCC was associated with improved survival in patients with metastatic osteosarcoma in California. However, we found disparities in the delivery of GCC, highlighting the need for target interventions to improve delivery of GCC in this patient population.

PMID:38381995 | DOI:10.1200/OP.23.00591

J Clin Oncol. 2024 Feb 21:JCO2302112. doi: 10.1200/JCO.23.02112. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).

PATIENTS AND METHODS: Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2- advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator’s choice of ET (n = 239).

RESULTS: In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia.

CONCLUSION: The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

PMID:38381994 | DOI:10.1200/JCO.23.02112