Tag: statistics

JAMA Oncol. 2023 Apr 20. doi: 10.1001/jamaoncol.2023.0356. Online ahead of print.

ABSTRACT

IMPORTANCE: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.

OBJECTIVE: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.

DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020.

INTERVENTIONS: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below.

MAIN OUTCOMES AND MEASURES: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord.

RESULTS: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00922974.

PMID:37079324 | DOI:10.1001/jamaoncol.2023.0356

JAMA Oncol. 2023 Apr 20. doi: 10.1001/jamaoncol.2023.0260. Online ahead of print.

ABSTRACT

IMPORTANCE: Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.

OBJECTIVE: To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.

DATA SOURCES: A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.

STUDY SELECTION: Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.

DATA EXTRACTION AND SYNTHESIS: This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.

MAIN OUTCOMES AND MEASURES: The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.

RESULTS: Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.

PMID:37079318 | DOI:10.1001/jamaoncol.2023.0260

Minerva Anestesiol. 2023 Apr 20. doi: 10.23736/S0375-9393.23.17080-5. Online ahead of print.

ABSTRACT

BACKGROUND: Mechanical power (MP) is the amount of energy transferred from the ventilator to the patient within a unit of time. It has been emphasized in ventilation-induced lung injury (VILI) and mortality. However, its measurement and use in clinical practice are challenging. “Electronic recording systems (ERS)” using mechanical ventilation parameters provided by the ventilator can be helpful to measure and record the MP. The MP (J/minutes) formula is 0.098 x tidal volume x respiratory rate x (Ppeak – ½ ∆P), in which ∆P is the driving pressure and Ppeak is the peak pressure. We aimed to define the association between MP values and ICU mortality, mechanical ventilation days, and intensive care unit length of stay (ICU-LOS). The secondary outcome was to determine the most potent or essential component of power in the equation that has a role in mortality.

METHODS: This retrospective study was performed in two centers (VKV American Hospital and Bakırköy Sadi Konuk Hospital ICUs) that used ERS (Metavision IMDsoft) between 2014 and 2018. We uploaded the power formula (MP (J/minutes)=0.098×VT×RR×(Ppeak – ½ ∆P) to ERS (METAvision, iMDsoft, and Consult Orion Health) and calculated the MP value by using MV parameters automatically sent from the ventilator. (∆P; driving pressure, VT; tidal volume, RR; respiratory rate and Ppeak; peak pressure).

RESULTS: A total of 3042 patients were included in the study. The median value of MP was 11.3 J/min. Mortality in MP<11.3 J/min was 35.4%, and 49.1% in MP>11.3J/min.; P<0.001. Mechanical ventilation days and ICU-LOS were also statistically longer in the MVP>11.3 J/min group.

CONCLUSIONS: The first 24 h MP maybe a predictive value for the ICU patients’ prognosis. This implies that MP may be used as a decision-making system to define the clinical approach and as a scoring system to predict patient prognosis.

PMID:37079284 | DOI:10.23736/S0375-9393.23.17080-5

Anat Sci Int. 2023 Apr 20. doi: 10.1007/s12565-023-00727-5. Online ahead of print.

ABSTRACT

This study purposed to develop statistical models to predict palatal (PRL), mesial (MRL), and distal (DRL) root canal length and pulp volume (PV) of the maxillary first permanent molar using stature, gender, mesiodistal (MD), and buccopalatal (BP) crown diameters and some facial morphometries. 57 individuals were included in the study. Cone beam computed tomography was used to measure root canal lengths and PV. The PV calculation was carried out using the software ITK-SNAP 3.4.0. PRL was positively correlated with BP, stature, middle facial height, interalar distance, and bicommissural distance (BCD) (p < 0.05). DRL was positively correlated with BP, MD, and stature (p < 0.05). MRL was positively correlated with BP, MD, stature, lower face height, bizygomatic distance, and BCD (p < 0.05). PV was negatively correlated with age and BCD (p < 0.05). Although all models have significant predictive power for the root lengths and PV, no model could explain variances greater than 30%. The highest and lowest predictive ability was obtained for PRL and DRL, respectively. While the most significant predictor was BP for PRL and DRL, it was the age for PV.

PMID:37079264 | DOI:10.1007/s12565-023-00727-5

Environ Sci Pollut Res Int. 2023 Apr 20. doi: 10.1007/s11356-023-26813-9. Online ahead of print.

ABSTRACT

Exposure to arsenic even at low levels can lead to adverse health outcomes, however, there is a paucity of research from South Africa in relation to human exposure to arsenic. We investigated long-term exposure of residents in Limpopo province, South Africa, in a cross-sectional study by analysing water, soil and blood arsenic concentrations from two arsenic-exposed (high and medium-low exposure) villages and one non-exposed (control) village. There were statistically significant differences in the distribution of arsenic in water, soil and blood amongst the three sites. The median drinking water arsenic concentration in the high-exposure village was 1.75 µg/L (range = 0.02 to 81.30 µg/L), 0.45 µg/L (range = 0.100 to 6.00 µg/L) in the medium- / low-exposure village and 0.15 µg/L (range = < limit of detection (LOD) to 29.30 µg/L) in the control site. The median soil arsenic concentration in the high-exposure village was 23.91 mg/kg (range = < LOD to 92.10 mg/kg) whilst arsenic concentrations were below the limit of detection in all soil samples collected from the medium-/low-exposure and control villages. In the high-exposure village, the median blood arsenic concentration was 1.6 µg/L (range = 0.7 to 4.2 µg/L); 0.90 µg/L (range = < LOD to 2.5 µg/L) in the medium-/low-exposure village and 0.6 µg/L (range = < LOD to 3.3 µg/L) in the control village. Significant percentages of drinking water, soil and blood samples from the exposed sites were above the internationally recommended guidelines (namely, 10 µg/L, 20 mg/kg and 1 µg/L, respectively). Majority of participants (86%) relied on borehole water for drinking and there was a significant positive correlation between arsenic in blood and borehole water (p-value = 0.031). There was also a statistically significant correlation between arsenic concentrations in participants’ blood and soil samples collected from gardens (p-value = 0.051). Univariate quantile regression found that blood arsenic concentrations increased by 0.034 µg/L (95% CI = 0.02-0.05) for each one unit increase in water arsenic concentrations (p < 0.001). After adjusting for age, water source and homegrown vegetable consumption in multivariate quantile regression, participants from the high-exposure site had significantly higher blood concentrations than those in the control site (coefficient: 1.00; 95% CI = 0.25-1.74; p-value = 0.009) demonstrating that blood arsenic is a good biomarker of arsenic exposure. Our findings also provide new evidence for South Africa on the association between drinking water and arsenic exposure, emphasising the need for the provision of potable water for human consumption in areas with high environmental arsenic concentrations.

PMID:37079235 | DOI:10.1007/s11356-023-26813-9

Geroscience. 2023 Apr 20. doi: 10.1007/s11357-023-00785-7. Online ahead of print.

ABSTRACT

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo-derived senescence signature (SenSig) using a foreign body response-driven fibrosis model in a p16-CreER^T2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type-specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34-CSF1R-TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.

PMID:37079217 | DOI:10.1007/s11357-023-00785-7

Tissue Eng Regen Med. 2023 Apr 20. doi: 10.1007/s13770-023-00534-z. Online ahead of print.

ABSTRACT

BACKGROUND: In guided bone regeneration (GBR), there are various problems that occur in the bone defect after the wound healing period. This study aimed to investigate the enhancement of the osteogenic ability of the dual scaffold complex and identify the appropriate concentration of growth factors (GF) for new bone formation based on the novel GBR concept that is applying rapid bone forming GFs to the membrane outside of the bone defect.

METHODS: Four bone defects with a diameter of 8 mm were formed in the calvaria of New Zealand white rabbits each to perform GBR. Collagen membrane and biphasic calcium phosphate (BCP) were applied to the bone defects with the four different concetration of BMP-2 or FGF-2. After 2, 4, and 8 weeks of healing, histological, histomorphometric, and immunohistochemical analyses were conducted.

RESULTS: In the histological analysis, continuous forms of new bones were observed in the upper part of bone defect in the experimental groups, whereas no continuous forms were observed in the control group. In the histomorphometry, The group to which BMP-2 0.5 mg/ml and FGF-2 1.0 mg/ml was applied showed statistically significantly higher new bone formation. Also, the new bone formation according to the healing period was statistically significantly higher at 8 weeks than at 2, 4 weeks.

CONCLUSION: The novel GBR method in which BMP-2, newly proposed in this study, is applied to the membrane is effective for bone regeneration. In addition, the dual scaffold complex is quantitatively and qualitatively advantageous for bone regeneration and bone maintenance over time.

PMID:37079199 | DOI:10.1007/s13770-023-00534-z

EJNMMI Phys. 2023 Apr 20;10(1):29. doi: 10.1186/s40658-023-00548-5.

ABSTRACT

PURPOSE: In this retrospective study, we compared the maximum standardized uptake values (SUVmax) of parathyroid lesions and the target-to-background ratio (TBR) of parathyroid lesions to thyroid tissue in early-phase single-photon emission computed tomography/computed tomography (SPECT/CT) versus delayed-phase SPECT/CT in patients with secondary hyperparathyroidism (SHPT) in order to determine the optimal timing of 99mTc- methoxyisobutylisonitrile (99mTc-MIBI) SPECT/CT imaging.

METHODS: Seventeen patients with a history of chronic kidney failure stage 5 on hemodialysis, underwent pre-operative parathyroid scintigraphy for detection and localization of parathyroid lesions. Retrospective analysis was conducted for lesions with focal accumulation of 99mTc-MIBI. All patients underwent dual-phase 99mTc-MIBI parathyroid scintigraphy and dual-phase SPECT/CT. SUVmax of parathyroid lesions and thyroid tissues was measured.

RESULTS: Mean SUVmax of parathyroid lesions was 4.86 on early-phase and 2.58 on delayed-phase SPECT/CT, respectively. Mean TBR was 1.14 on early phase and 1.48 on delayed-phase SPECT/CT, respectively. Statistically significant differences in SUVmax and TBR between dual-phase SPECT/CT were observed (P < 0.001).

CONCLUSIONS: Delayed-phase SPECT/CT in SHPT is required because of the better image contrast.

PMID:37079194 | DOI:10.1186/s40658-023-00548-5

Egypt Heart J. 2023 Apr 20;75(1):29. doi: 10.1186/s43044-023-00356-3.

ABSTRACT

BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA).

METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices.

RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = – 0.66; 95% CI (- 1.01, – 0.32) and SMD = – 0.56; 95% CI (- 0.73, – 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis.

CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.

PMID:37079174 | DOI:10.1186/s43044-023-00356-3

Ecotoxicology. 2023 Apr 20. doi: 10.1007/s10646-023-02645-8. Online ahead of print.

ABSTRACT

Highly imperiled unionids have a complex life cycle including the metamorphosis of an obligate parasite life stage, larval glochidia, to the juvenile stage. Despite the known vulnerabilities of both glochidia and juveniles to pollutants, little is known on how metamorphosis success may be affected by chemical stress. Disruption of the transformation process in which glochidia encyst on the gills of a host fish, could lead to lowered recruitment and population declines. Transformation rates of Lampsilis cardium on host fish Micropterus salmoides were empirically derived from experimental exposures to low, medium, or high concentrations of an agricultural or urban mixture of contaminants of emerging concern (CECs) over two exposure durations. Transformation was characterized by: (1) a zero-inflated Poisson general linear mixed effects model to compare difference in transformation between exposure durations and (2) time response curves to describe the transformation curve using long-term exposure data. Lampsilis cardium transformation was similar between exposure durations. When compared to controls, CEC stress significantly reduced juvenile production (p « 0.05) except for the agricultural medium treatment and tended to increased encapsulation duration which while statistically insignificant (p = 0.16) may have ecological relevancy. Combining the empirically derived reduction of transformation rates with parameters values from the literature, a Lefkovich stage-based population model predicted strong declines in population size of L. cardium for all treatments if these results hold in nature. Management focus on urban CECs may lead to best conservation efforts though agricultural CECs may also have a concentration dependent impact on transformation and therefore overall recruitment and conservation success.

PMID:37079163 | DOI:10.1007/s10646-023-02645-8