Category: Statistics

ASAIO J. 2024 Jan 8. doi: 10.1097/MAT.0000000000002128. Online ahead of print.

ABSTRACT

The Extracorporeal Life Support Organization (ELSO) maintains the world’s largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

PMID:38181413 | DOI:10.1097/MAT.0000000000002128

Phys Rev Lett. 2023 Dec 22;131(25):250401. doi: 10.1103/PhysRevLett.131.250401.

ABSTRACT

Ergodicity of quantum dynamics is often defined through statistical properties of energy eigenstates, as exemplified by Berry’s conjecture in single-particle quantum chaos and the eigenstate thermalization hypothesis in many-body settings. In this work, we investigate whether quantum systems can exhibit a stronger form of ergodicity, wherein any time-evolved state uniformly visits the entire Hilbert space over time. We call such a phenomenon complete Hilbert-space ergodicity (CHSE), which is more akin to the intuitive notion of ergodicity as an inherently dynamical concept. CHSE cannot hold for time-independent or even time-periodic Hamiltonian dynamics, owing to the existence of (quasi)energy eigenstates which precludes exploration of the full Hilbert space. However, we find that there exists a family of aperiodic, yet deterministic drives with minimal symbolic complexity-generated by the Fibonacci word and its generalizations-for which CHSE can be proven to occur. Our results provide a basis for understanding thermalization in general time-dependent quantum systems.

PMID:38181361 | DOI:10.1103/PhysRevLett.131.250401

Phys Rev Lett. 2023 Dec 22;131(25):257301. doi: 10.1103/PhysRevLett.131.257301.

ABSTRACT

The Hopfield model is a paradigmatic model of neural networks that has been analyzed for many decades in the statistical physics, neuroscience, and machine learning communities. Inspired by the manifold hypothesis in machine learning, we propose and investigate a generalization of the standard setting that we name random-features Hopfield model. Here, P binary patterns of length N are generated by applying to Gaussian vectors sampled in a latent space of dimension D a random projection followed by a nonlinearity. Using the replica method from statistical physics, we derive the phase diagram of the model in the limit P,N,D→∞ with fixed ratios α=P/N and α_{D}=D/N. Besides the usual retrieval phase, where the patterns can be dynamically recovered from some initial corruption, we uncover a new phase where the features characterizing the projection can be recovered instead. We call this phenomena the learning phase transition, as the features are not explicitly given to the model but rather are inferred from the patterns in an unsupervised fashion.

PMID:38181351 | DOI:10.1103/PhysRevLett.131.257301

Phys Rev Lett. 2023 Dec 22;131(25):251803. doi: 10.1103/PhysRevLett.131.251803.

ABSTRACT

We present the first data-driven result for a_{μ}^{win,lqc}, the isospin-limit light-quark connected component of the intermediate-window Hadronic-vacuum-polarization contribution to the muon anomalous magnetic moment. Our result, (198.8±1.1)×10^{-10}, is in significant tension with eight recent mutually compatible high-precision lattice-QCD determinations, and provides enhanced evidence for a puzzling discrepancy between lattice and data-driven determinations of the intermediate-window quantity, one driven largely by a difference in the light-quark connected component.

PMID:38181347 | DOI:10.1103/PhysRevLett.131.251803

Phys Rev Lett. 2023 Dec 22;131(25):254201. doi: 10.1103/PhysRevLett.131.254201.

ABSTRACT

Evaporation of cloud droplets accelerates when turbulence mixes dry air into the cloud, affecting droplet-size distributions in atmospheric clouds, combustion sprays, and jets of exhaled droplets. The challenge is to model local correlations between droplet numbers, sizes, and supersaturation, which determine supersaturation fluctuations along droplet paths (Lagrangian fluctuations). We derived a statistical model that accounts for these correlations. Its predictions are in quantitative agreement with results of direct numerical simulations, and explain the key mechanisms at play.

PMID:38181342 | DOI:10.1103/PhysRevLett.131.254201

Neurology. 2024 Feb 13;102(3):e208035. doi: 10.1212/WNL.0000000000208035. Epub 2024 Jan 5.

ABSTRACT

BACKGROUND AND OBJECTIVES: Risk of readmission after stroke differs by stroke (sub)type and etiology, with higher risks reported for hemorrhagic stroke and cardioembolic stroke. We examined the risk and cause of first readmission by stroke subtype over the years post incident stroke.

METHODS: Atherosclerosis Risk in Communities (ARIC) study participants (n = 1,412) with first-ever stroke were followed up for all-cause readmission after incident stroke. Risk of first readmission was examined by stroke subtypes (cardioembolic, thrombotic/lacunar, and hemorrhagic [intracerebral and subarachnoid]) using Cox and Fine-Gray proportional hazards models, adjusting for sociodemographic and cardiometabolic risk factors.

RESULTS: Among 1,412 participants (mean [SD] age 72.4 [9.3] years, 52.1% women, 35.3% Black), 1,143 hospitalizations occurred over 41,849 person-months. Overall, 81% of participants were hospitalized over a maximum of 26.6 years of follow-up (83% of participants with thrombotic/lacunar stroke, 77% of participants with cardioembolic stroke, and 78% of participants with hemorrhagic stroke). Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions. Over the entire follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (hazard ratio [HR] 0.82, 95% CI 0.71-0.95) and hemorrhagic stroke (HR 0.74, 95% CI 0.58-0.93) in adjusted Cox proportional hazards models. By contrast, there was no statistically significant difference among subtypes when adjusting for atrial fibrillation and competing risk of death. Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (HR 0.66, 95% CI 0.46-0.93) and during 1 month-1 year (HR 0.78, 95% CI 0.62-0.97), and hemorrhagic stroke was associated with lower risk during 1 month-1 year (HR 0.60, 95% CI 0.41-0.87). There was no significant difference between subtypes in readmission risk during later periods.

DISCUSSION: Over 26 years of follow-up, 81% of stroke participants experienced a readmission. Cardiovascular and cerebrovascular diagnoses at readmission were most common across stroke subtypes. Though cardioembolic stroke has previously been reported to confer higher risk of readmission, in this study, the readmission risk was not statistically significantly different between stroke subtypes or over different periods when accounting for the competing risk of death.

PMID:38181329 | DOI:10.1212/WNL.0000000000208035

JCO Clin Cancer Inform. 2024 Jan;8:e2300118. doi: 10.1200/CCI.23.00118.

ABSTRACT

PURPOSE: Limitations from commercial software applications prevent the implementation of a robust and cost-efficient high-throughput cancer imaging radiomic feature extraction and perfusion analysis workflow. This study aimed to develop and validate a cancer research computational solution using open-source software for vendor- and sequence-neutral high-throughput image processing and feature extraction.

METHODS: The Cancer Radiomic and Perfusion Imaging (CARPI) automated framework is a Python-based software application that is vendor- and sequence-neutral. CARPI uses contour files generated using an application of the user’s choice and performs automated radiomic feature extraction and perfusion analysis. This workflow solution was validated using two clinical data sets, one consisted of 40 pelvic chondrosarcomas and 42 sacral chordomas with a total of 82 patients, and a second data set consisted of 26 patients with undifferentiated pleomorphic sarcoma (UPS) imaged at multiple points during presurgical treatment.

RESULTS: Three hundred sixteen volumetric contour files were processed using CARPI. The application automatically extracted 107 radiomic features from multiple magnetic resonance imaging sequences and seven semiquantitative perfusion parameters from time-intensity curves. Statistically significant differences (P < .00047) were found in 18 of 107 radiomic features in chordoma versus chondrosarcoma, including six first-order and 12 high-order features. In UPS postradiation, the apparent diffusion coefficient mean increased 41% in good responders (P = .0017), while firstorder_10Percentile (P = .0312) was statistically significant between good and partial/nonresponders.

CONCLUSION: The CARPI processing of two clinical validation data sets confirmed the software application’s ability to differentiate between different types of tumors and help predict patient response to treatment on the basis of radiomic features. Benchmark comparison with five similar open-source solutions demonstrated the advantages of CARPI in the automated perfusion feature extraction, relational database generation, and graphic report export features, although lacking a user-friendly graphical user interface and predictive model building.

PMID:38181324 | DOI:10.1200/CCI.23.00118

JCO Precis Oncol. 2024 Jan;8:e2300441. doi: 10.1200/PO.23.00441.

ABSTRACT

PURPOSE: The way late-onset toxicities are managed can affect trial outcomes and participant safety. Specifically, participants often might not have completed their entire follow-up period to observe any toxicities before new participants would be recruited. We conducted a methodological review of published early-phase dose-finding clinical trials that used designs accounting for partial and complete toxicity information, aiming to understand (1) how such designs were implemented and reported and (2) if sufficient information was provided to enable the replicability of trial results.

METHODS: Until March 26, 2023, we identified 141 trials using the rolling 6 design, the time-to-event continuous reassessment method (TITE-CRM), the TITE-CRM with cycle information, the TITE Bayesian optimal interval design, the TITE cumulative cohort design, and the rapid enrollment design. Clinical settings, design parameters, practical considerations, and dose-limiting toxicity (DLT) information were extracted from these published trials.

RESULTS: The TITE-CRM (61, 43.3%) and the rolling 6 design (76, 53.9%) were most frequently implemented in practice. Trials using the TITE-CRM had longer DLT assessment windows beyond the first cycle compared with the rolling 6 design (52.5% v 6.6%). Most trials implementing the TITE-CRM (91.8%, 56 of 61) failed to describe essential parameters in the protocols or the study result papers. Only five TITE-CRM trials (8.2%, 5 of 61) reported sufficient information to enable replication of the final analysis.

CONCLUSION: When compared with trials using the rolling 6 design, those implementing the TITE-CRM design exhibited notable deficiencies in reporting essential details necessary for reproducibility. Inadequate reporting quality of advanced model-based trial designs hinders their credibility. We provide recommendations that can improve transparency, reproducibility, and accurate interpretation of the results for such designs.

PMID:38181316 | DOI:10.1200/PO.23.00441

Neurology. 2024 Feb 13;102(3):e207809. doi: 10.1212/WNL.0000000000207809. Epub 2024 Jan 5.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of CYP2C19 loss-of-function alleles, dual-antiplatelet therapy with ticagrelor-aspirin reduced the 90-day risk of stroke without increased severe or moderate bleeding compared with clopidogrel-aspirin. However, whether dual-antiplatelet therapy with ticagrelor was superior to clopidogrel beyond the 90 days of follow-up remained unclear. In this study, we reported 1-year follow-up outcomes of the CHANCE-2 trial.

METHODS: The CHANCE-2 trial is a randomized, double-blind, placebo-controlled trial at 202 centers in China. Patients with a minor stroke or TIA who carried CYP2C19 loss-of-function alleles were randomized within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor and placebo clopidogrel or to receive clopidogrel and placebo ticagrelor for 90 days; both groups received aspirin for the first 21 days. After day 90, treatment was as per the choice of the clinician and the patient.

RESULTS: Among 6,412 patients, the proportion of patients on ticagrelor plus aspirin, clopidogrel plus aspirin, ticagrelor alone, clopidogrel alone, aspirin alone, other antiplatelet, and no antiplatelet beyond month 3 to 1 year was 0.09%, 1.56%, 0.13%, 2.66%, 73.65%, 0.78%, and 21.13% in the ticagrelor-aspirin group and 0.03%, 1.63%, 0.19%, 2.60%, 72.83%, 0.66%, and 22.06% in the clopidogrel-aspirin group, respectively. The primary outcome of new stroke occurred in 252 patients (7.91%) in the ticagrelor-aspirin group and 310 patients (9.73%) in the clopidogrel-aspirin group by 1 year of follow-up (hazard ratio 0.80; 95% CI 0.68-0.95; p = 0.007); new stroke beyond 3 months to 1 year occurred in 61 patients (2.07%) and 67 patients (2.32%) (p = 0.48), respectively. Primary safety outcome of severe or moderate bleeding occurred in 17 patients (0.53%) in the ticagrelor-aspirin group and 20 patients (0.63%) in the clopidogrel-aspirin group (p = 0.61).

DISCUSSION: For CYP2C19 loss-of-function allele carriers, early dual-antiplatelet therapy with ticagrelor is superior to clopidogrel at 1 year in reducing recurrent stroke.

TRIAL REGISTRATION INFORMATION: URL: clinicaltrials.gov. Unique identifier: NCT04078737.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with minor stroke or TIA with TIACYP2C19 loss-of-function, ticagrelor plus aspirin for 21 days is superior to clopidogrel plus aspirin in reducing the 1-year risk of recurrent stroke.

PMID:38181311 | DOI:10.1212/WNL.0000000000207809

JCO Glob Oncol. 2024 Jan;10:e2300312. doi: 10.1200/GO.23.00312.

ABSTRACT

PURPOSE: The cost of immune checkpoint inhibitors (ICIs) limits their accessibility to a small number of patients with cancer in low- and middle-income countries. Early-phase clinical trials have shown target inhibition and high activity at doses lower than those registered and evaluated in clinical trials. Here, we report everyday experience of using ICIs in 100 Indian patients, many of whom received lower doses of ICIs.

METHODS: Consecutive patients who received at least one dose of an ICI irrespective of tumor type at a tertiary care hospital in Mumbai, India, that was able to access ICIs for its patients were enrolled. The objectives were to study the doses used over a 3-year time period, and the effectiveness of therapy, assessed primarily by the overall response rate (ORR), overall survival (OS), and progression-free survival were secondary end points.

RESULTS: Twenty-five patients were treated with conventional doses of ICIs, 29 patients received lower doses per body weight, and 46 patients received low-dose treatment. The median number of cycles received was 5 (range, 1-28). Seventy-eight patients received ICIs in a palliative setting. The median follow-up time was 10.2, 9.8, and 3.9 months for those receiving fixed approved dosing, per body weight dosing, and low-dose treatment, respectively. There was a trend with time to prescribe lower doses. Response evaluation was available for 92 patients. Twenty-one (five-adjuvant and 16-palliative) patients received ICIs only. The ORR did not differ statistically among different dosing groups, but comparisons are confounded by inclusion of different ICIs, different tumor sites, and concurrent treatments. The median OS was 6.8 (range, 4.6-9.0) months.

CONCLUSION: Adoption of per-body weight and lower dosing of ICIs appears to give acceptable outcomes. Lower dosing can improve access and timely delivery of ICIs in low- and middle-income countries.

PMID:38181308 | DOI:10.1200/GO.23.00312