Category: Statistics

JCO Glob Oncol. 2025 Jan;11:e2400464. doi: 10.1200/GO-24-00464. Epub 2025 Jan 30.

ABSTRACT

PURPOSE: Prior noncontemporary studies showed that oral cyclophosphamide is an active treatment of metastatic castration-resistant prostate cancer (mCRPC). However, cyclophosphamide is currently underutilized in routine clinical practice given the lack of survival benefit and the emergence of more effective treatments.

METHODS: We retrospectively reviewed our institutional database to identify patients with mCRPC treated with cyclophosphamide. Prostate-specific antigen decrease ≥50% from baseline (PSA50) response was determined as the proportion of patients achieving a prostate-specific antigen (PSA) decline ≥50% from baseline. Radiographic responses and progression were evaluated by Prostate Cancer Working Group 3. Survival estimates used the Kaplan-Meier method, and correlations were made with Chi-square test for categorical variables.

RESULTS: From January 2011 to January 2023, 341 patients with mCRPC received oral cyclophosphamide at a tertiary cancer center in São Paulo, Brazil. The most common regimen (95%) was 100 mg once daily 21 days on, 7 days off. At prostate cancer diagnosis, the median age was 64.4 years (IQR, 59.4-70.8), 61.9% had metastatic de novo disease, and 55.5% had Gleason ≥8. The median number of previous treatment lines was three (IQR, 2-4). Any PSA decline was observed in 33.4%, and 13.2% had a PSA50 response. Median response duration was 2.1 months (IQR, 1.4-3.8). Ten patients (3%) were treated for ≥1 year. PSA50 response was associated with no prior docetaxel use and Eastern Cooperative Oncology Group performance status 0 or 1.

CONCLUSION: Oral cyclophosphamide is a feasible treatment option for patients with mCRPC, particularly in a scenario of limited health care resources.

PMID:39883895 | DOI:10.1200/GO-24-00464

JCO Glob Oncol. 2025 Jan;11:e2400320. doi: 10.1200/GO-24-00320. Epub 2025 Jan 30.

ABSTRACT

PURPOSE: The academic field of global pediatric oncology is expanding as cancer becomes increasingly recognized as a global health priority for children and adolescents. Here, we aimed to explore the representation of authors, the geographic distribution of research, and the research approaches being used in global pediatric oncology.

METHODS: Articles published in JCO Global Oncology (JCO GO) and Pediatric Blood and Cancer on the topic of global pediatric oncology were analyzed. For each article, data were collected on the study design, the research location, and the authorship demographics. Descriptive frequencies were reported for all items.

RESULTS: Overall, 296 studies met the inclusion criteria to be considered relevant for global pediatric oncology. Of these, 259 (87.5%) were research articles. Of the research articles, 228 (88.0%) were observational and 117 (51.3%) were retrospective cohort analyses. Thirty-eight studies (12.8%) had a global focus or were unrelated to a geographic context, 54 (18.2%) were regional, and 204 (68.9%) were specific to a single country. Females represented 163 (55.8%) of first authors, 138 (46.6%) of senior authors, and 159 (53.7%) of corresponding authors. Furthermore, 121 (41.4%) first authors, 163 (55.1%) last authors, and 142 (48.0%) senior authors were from high-income countries (HICs). The United States (n = 81) and India (n = 40) had the most corresponding authors. Thirty-six (17.6%) articles had research conducted in low- and middle-income countries (LMICs), and the first, senior, and corresponding authors were from HICs.

CONCLUSION: Our analysis shows that researchers from LMICs are under-represented as authors of global pediatric oncology publications. Further studies are needed to evaluate the factors that contribute to inequalities in global pediatric oncology research.

PMID:39883894 | DOI:10.1200/GO-24-00320

J Clin Oncol. 2025 Jan 30:JCO2401360. doi: 10.1200/JCO-24-01360. Online ahead of print.

ABSTRACT

PURPOSE: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

METHODS: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination R² from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

RESULTS: Eleven RCTs, for a total of 15 treatment comparisons and 12,247 patients, were included in the analysis. There was a weak association between hazard ratios (HRs) for OS and odds ratio of pCR overall (R², 0.07; 95% CI, 0.00 to 0.48), as well as in all the subgroups explored. Overall, the R² for the association between HR OS and HR iDFS was 0.46 (95% CI, 0.08 to 0.71), which is just below the cutoff of 0.5 for moderate surrogacy. In the majority of subgroups explored, the R² ranged from 0.5 to <0.7, while in hormone receptor-/human epidermal growth factor receptor 2- subtype, histologic grade 1-2 tumors, and lobular tumors, surrogacy was strong (ie, R² ≥0.7). The surrogacy value of iDFS for OS was affected by follow-up (FUP) length: R² substantially increased up to 36 months of FUP, with little further improvement after 48 months of FUP.

CONCLUSION: iDFS with sufficient FUP is an acceptable surrogate end point to confidently anticipate final OS results of neoadjuvant RCTs for early BC. This recommendation holds true across many subgroups, with the notable exception of HR+ disease. There is definite need to reassess whether OS is the optimal end point for treatment efficacy measurement in HR+ early BC.

PMID:39883887 | DOI:10.1200/JCO-24-01360

Am J Hosp Palliat Care. 2025 Jan 30:10499091251317174. doi: 10.1177/10499091251317174. Online ahead of print.

ABSTRACT

PURPOSE: To determine the feasibility of mapping interdisciplinary role ownership over actionable practices identified from qualitative comments in the Veterans Affairs Bereaved Family Survey (BFS).

METHODS: We polled two providers from each of 14 disciplines as to whether an actionable practice that improved end-of-life care quality sits within their scope of practice. We grouped practices by having the greatest, middle, and fewest number of disciplines that claimed role ownership and then characterized what roles were shared.

MAJOR FINDINGS: Medicine, nursing, social work, and occupational therapy claimed role ownership of the greatest number of practices among the 14 disciplines. Chaplaincy and the allied health disciplines had a comparatively more limited range of role ownership of practices. Practices with the greatest number of professionals claiming role ownership were general professional behaviors that do not require specialized training (e.g., being easy to talk to). Practices with the middle number of role ownership required clinical specialization (e.g., offering non-pharmacological interventions to reduce agitation). Practices with the fewest number of disciplines required a narrower skill set (e.g., signing the death certificate in a timely manner) or administrative authority to perform (e.g., providing adequate nursing staff).

CONCLUSIONS: This project demonstrated the feasibility of mapping BFS actionable practices across disciplines. A larger sample and rigorous statistical analysis are required for application at a health care system level. Understanding role ownership can then guide efforts relating to role ownership and role sharing for end-of-life quality improvement activities.

PMID:39883885 | DOI:10.1177/10499091251317174

J Glob Health. 2025 Jan 31;15:04023. doi: 10.7189/jogh.15.04023.

ABSTRACT

BACKGROUND: The prevalence of antibiotic prescribing among total prescriptions, the percentage of combined antibiotic prescribing among prescriptions containing at least one antibiotic, and factors influencing hospital antibiotic prescribing are currently unknown. In this systematic review, we aimed to summarise antibiotic prescribing in hospitals worldwide and identify the associated factors.

METHODS: We searched PubMed/MEDLINE, Ovid/Embase, and the Web of Science for articles published between 1 January 2000 and 28 February 2023 that reported antibiotic prescribing in hospitals or the associated factors. Four reviewers independently screened studies, extracted data, and assessed the risk of bias. We used meta-analysis with random-effects models to estimate the pooled effect sizes.

RESULTS: We included 403 studies covering 93 economies. The pooled prevalence of antibiotic prescribing among total prescriptions was 34.3% (95% CI = 29.6-39.3) in outpatient settings and 47.7% (95% CI = 45.8-49.5) in inpatient settings. The pooled percentages of antibiotics in the ‘access’ group were 48.5% (95% CI = 34.5-62.7) in outpatient settings and 43.8% (95% CI = 39.2-48.5) in inpatient settings. Subgroup analysis showed the prevalence of antibiotic prescribing was significantly higher in low-income compared to high-income economies. Additionally, there was a rising trend of the prevalence in inpatient settings over time. The studies showed that patients’ gender, education level, health status, and physicians’ work experience were associated with hospital antibiotic prescribing.

CONCLUSIONS: The global prevalence of antibiotic prescribing in hospitals is high, with significant disparities across regions. Multifaceted measures with multi-sectoral cooperation are required, such as regulatory interventions, professional training for physicians, and public health education.

REGISTRATION: PROSPERO: CRD42022354076.

PMID:39883879 | DOI:10.7189/jogh.15.04023

J Int Med Res. 2025 Jan;53(1):3000605241311405. doi: 10.1177/03000605241311405.

ABSTRACT

OBJECTIVES: Central nervous system complications of acute pancreatitis (AP) can result in cerebral edema (CE). We assessed the risk of serious outcomes and health care features associated with CE in patients hospitalized with AP.

METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database. Patients were divided into the AP-CE group that developed CE and the AP-only group that did not. Outcome data were analyzed using Stata software.

RESULTS: Among 543,464 patients hospitalized with AP, 220 (0.04%) developed CE. In multivariate analysis, primary outcomes included increased length of hospital stay (adjusted odds ratio [aOR] 10.1; 95% confidence interval [CI] 0.50-19.70), hospital charges (aOR USD 208,713; 95% CI 27,095-390,330), and risk of death (aOR 17.17; 95% CI 5.88-50.07) in the AP-CE group. Secondary outcomes showed patients with AP-CE had a significantly increased risk of serious complications, particularly cardiac arrest (aOR 64.24; 95% CI 24.27-170.02), and higher hospital resource utilization.

CONCLUSION: Patients with AP who develop CE face worse outcomes, including increased mortality risk, prolonged hospital stay, and greater resource utilization. Timely identification and effective management of CE in AP may reduce mortality and ease the health care burden associated with this neurological complication.

PMID:39883809 | DOI:10.1177/03000605241311405

Science. 2025 Jan 31;387(6733):464-467. doi: 10.1126/science.adw3275. Epub 2025 Jan 30.

ABSTRACT

A small statistical agency within the U.S. Department of Agriculture was torn apart under Trump-and then rebuilt. What did it lose, and what can other U.S. research agencies learn from it?

PMID:39883767 | DOI:10.1126/science.adw3275

Science. 2025 Jan 31;387(6733):522-527. doi: 10.1126/science.adr8891. Epub 2025 Jan 30.

ABSTRACT

Phase diagrams and crystallography are standard tools for studying structural phase transitions, whereas acquiring kinetic information at the atomistic level has been considered essential but challenging. The η-to-θ phase transition of alumina is unidirectional in bulk and retains the crystal lattice orientation. We report a rare example of a statistical kinetics study showing that for nanoparticles on a bulk Al(OH)₃ surface, this phase transition occurs nondeterministically through an ergodic equilibrium through the molten state, and the memory of the lattice orientation is lost in this process. The rate of the interconversion was found to be insensitive to the electron dose rate, and this process had a small Gibbs free energy of activation. These nondeterministic kinetics should be a key feature of crystal nucleation occurring in high-surface-energy regions of bulk crystals.

PMID:39883752 | DOI:10.1126/science.adr8891

PLoS One. 2025 Jan 30;20(1):e0305787. doi: 10.1371/journal.pone.0305787. eCollection 2025.

ABSTRACT

OBJECTIVES: Hearing impairment can have major impacts on behavior, educational attainment, social status, and quality of life. In congenital hypothyroidism, the incidence of hearing impairment reaches 35-50%, while in acquired hypothyroidism there is a reported incidence of 25%. Despite this, knowledge of the pathogenesis, incidence and severity of hearing impairment remains greatly lacking. The aim of our study was to evaluate hearing in patients with acquired hypothyroidism.

METHODS: 30 patients with untreated and newly diagnosed peripheral hypothyroidism (H) and a control group of 30 healthy probands (C) were enrolled in the study. Biochemical markers were measured, including median iodine urine concentrations (IUC) µg/L. The hearing examination included a subjective complaint assessment, otomicroscopy, tympanometry, transitory otoacoustic emission (TOAE), tone audiometry, and brainstem auditory evoked potential (BERA) examinations. The Mann-Whitney U test, Fisher’s Exact test and multivariate regression were used for statistical analysis.

RESULTS: The H and C groups had significantly different thyroid hormone levels (medians with 95% CI) TSH mU/L 13.3 (8.1, 19.3) vs. 1.97 (1.21, 2.25) p = 0 and fT4 pmol/L 10.4 (9.51, 11.1) vs. 15 (13.8, 16.7) p = 0. The groups did not significantly differ in age 39 (34, 43) vs. 41 (36,44) p = 0.767 and IUC 142 (113, 159) vs. 123 (101, 157) p = 0.814. None of the hearing examinations showed differences between the H and C groups: otomicroscopy (p = 1), tympanometry (p = 1), TOAE (p = 1), audiometry (p = 0.179), and BERA (p = 0.505).

CONCLUSIONS: We did not observe any hearing impairment in adults with acquired hypothyroidism, and there were no associations found between hearing impairment and the severity of hypothyroidism or iodine status. However, some forms of hearing impairment, mostly mild, were very common in both studied groups.

PMID:39883737 | DOI:10.1371/journal.pone.0305787

Biomacromolecules. 2025 Jan 30. doi: 10.1021/acs.biomac.4c01598. Online ahead of print.

ABSTRACT

2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) structures possess potent antioxidant activities for biomedical applications. TEMPO immobilization on hydrophilic polymers is a powerful strategy to improve its properties; however, it is mostly limited to reversible-deactivation radical polymerizations or postpolymerization approaches. Here, we immobilized TEMPO units on a hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) backbone through cationic ring-opening polymerization (CROP) of a new 2-oxazoline monomer bearing a methoxy-protected TEMPO 2-substituent with 2-ethyl-2-oxazoline (EtOx). The ratios of EtOx/TempOx were adjusted to optimize the nitroxide content while maintaining suitable water solubility of the resulting P(EtOx_x-stat-TempOx-O_y^•) copolymers upon deprotection. P(EtOx₄₀-stat-TempOx-O₁₀^•) and P(EtOx₃₃-stat-TempOx-O₁₇^•) showed a dual stimuli-responsive behavior and demonstrated significant radical-trapping activities in aqueous media. Particularly, a meaningful augmentation in the activity of TempOx-O^• was observed when it was immobilized as P(EtOx_x-stat-TempOx-O_y^•). The P(EtOx₄₀-stat-TempOx-O₁₀^•) system exhibited a longer-lasting activity in water, statistically comparable to that of the antioxidant ferrostatin-1 (Fer-1). Overall, this study introduces a biocompatible polymeric platform for TEMPO immobilization that augments its radical-trapping activity and offers controllable stimuli-responsive properties.

PMID:39883722 | DOI:10.1021/acs.biomac.4c01598