Tag: statistics

JCO Oncol Pract. 2024 May 28:OP2400036. doi: 10.1200/OP.24.00036. Online ahead of print.

ABSTRACT

PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described.

METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley’s databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed.

RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P = .04) and poorer overall survival (28 v 45 months, P = .04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences.

CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes.

PMID:38805663 | DOI:10.1200/OP.24.00036

Artif Life. 2024 May 27:1-15. doi: 10.1162/artl_a_00440. Online ahead of print.

ABSTRACT

This work concerns the long-term collective excitability properties and the statistical analysis of the critical events displayed by a recently introduced spatiotemporal many-body model, proposed as a new paradigm for Artificial Life. Numerical simulations show that excitable collective structures emerge in the form of dynamic networks, created by bursts of spatiotemporal activity (avalanches) at the edge of a synchronization phase transition. The spatiotemporal dynamics is portraited by a movie and quantified by time varying collective parameters, showing that the dynamic networks undergo a “life cycle,” made of self-creation, homeostasis, and self-destruction. The power spectra of the collective parameters show 1/f power law tails. The statistical properties of the avalanches, evaluated in terms of size and duration, show power laws with characteristic exponents in agreement with those values experimentally found in the neural networks literature. The mechanism underlying avalanches is argued in terms of local-to-collective excitability. The connections that link the present work to self-organized criticality, neural networks, and Artificial Life are discussed.

PMID:38805660 | DOI:10.1162/artl_a_00440

Mol Pharm. 2024 May 28. doi: 10.1021/acs.molpharmaceut.4c00086. Online ahead of print.

ABSTRACT

Block copolymers, composed of poly(2-oxazoline)s and poly(2-oxazine)s, can serve as drug delivery systems; they form micelles that carry poorly water-soluble drugs. Many recent studies have investigated the effects of structural changes of the polymer and the hydrophobic cargo on drug loading. In this work, we combine these data to establish an extended formulation database. Different molecular properties and fingerprints are tested for their applicability to serve as formulation-specific mixture descriptors. A variety of classification and regression models are built for different descriptor subsets and thresholds of loading efficiency and loading capacity, with the best models achieving overall good statistics for both cross- and external validation (balanced accuracies of 0.8). Subsequently, important features are dissected for interpretation, and the DrugBank is screened for potential therapeutic use cases where these polymers could be used to develop novel formulations of hydrophobic drugs. The most promising models are provided as an open-source software tool for other researchers to test the applicability of these delivery systems for potential new drug candidates.

PMID:38805643 | DOI:10.1021/acs.molpharmaceut.4c00086

Fam Med. 2024 May 20. doi: 10.22454/FamMed.2024.991075. Online ahead of print.

ABSTRACT

BACKGROUND: Academic family medicine (FM) physicians aim to balance competing needs of providing clinical care with nonclinical duties of program administration, formal education, and scholarly activity. FM residency is unique in its scope of practice, clinical settings, and training priorities, which may differ between university-based and community-based programs. In both types of programs, these competing needs are a source of faculty dissatisfaction and burnout. We performed this study to explore the allocation of nonclinical administrative full-time equivalents (FTE) for FM residency core faculty members.

RESULTS: Reported nonclinical administrative FTE time allocation is equivalent between university/medical school-based and community-based programs. The ideal proportion of FTE distribution identified by DCs had greater amounts of direct clinical care compared to greater emphasis on precepting time identified by PDs. DCs and PDs agreed that administrative time should be used for advising residents, curriculum development and delivery, and evaluation of resident performance. Barriers to allocating additional administrative time for DCs included loss of revenue and pressure by hospital-level leadership. PDs responded that the need for clinical supervision of residents was most significant.

METHODS: We performed our research through a cross-sectional survey of FM department chairs (DC) and residency program directors (PD) conducted by the Council of Academic Family Medicine Educational Research Alliance. We used descriptive statistics to characterize the data and Pearson’s χ2 tests to evaluate bivariate relationships.

CONCLUSIONS: DCs and PDs offer a similar ideal picture of core responsibilities, though subtle differences remain. These differences should be considered for the next revision of the Accreditation Council for Graduate Medical Education minimum program standards to best meet the needs of all FM programs.

PMID:38805632 | DOI:10.22454/FamMed.2024.991075

NEJM Evid. 2024 Apr;3(4):EVIDe2400022. doi: 10.1056/EVIDe2400022. Epub 2024 Mar 26.

NO ABSTRACT

PMID:38805616 | DOI:10.1056/EVIDe2400022

Ultrasound Obstet Gynecol. 2024 May 28. doi: 10.1002/uog.27710. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a prediction model for hypertensive disorders in pregnancy (HDP) and gestational diabetes (GDM) in twin pregnancies utilizing characteristics at the prenatal care entry level.

METHODS: Cross-sectional study using the US national live birth data between 2016 and 2021. The association of all prenatal candidate variables with HDP and GDM was tested with uni- and multi-variable logistic regression analyses. Prediction models were built with generalized linear models using the logit link function and classification and regression tree approach (XGboost) machine learning (ML) algorithm. Performance was assessed with repeated 2-fold cross-validation and performance metrics we considered were area under the curve (AUC). P value <0.001 was considered statistically significant.

RESULTS: A total of 707,198 twin pregnancies were included in the HDP analysis and 723,882 twin pregnancies for the GDM analysis. The incidence of HDP and GDM significantly increased from 12.2% in 2016 to 15.4% in 2021 and from 8.1% in 2016 to 10.7% in 2021, respectively. Factors that increase the risk of HDP in twin gestations are maternal age <20, age≥35, infertility, prepregnancy DM, non-Hispanic Black population, obesity, and those with Medicaid insurance (p<0.001). Factors that more than doubled the risk are obesity class II and III (p<0.001). Factors that increase the risk of GDM in twin gestations are age <25, age≥30, history of infertility, prepregnancy hypertension, non-Hispanic Asian population, non-US nativity, and obesity (p<0.001). Factors that more than doubled the risk are maternal age ≥ 30 years, non-Hispanic Asian, and class I, II, and III maternal obesity ( p<0.001). For both HDP and GDM, the performance of the ML and logistic regression model was mostly similar with negligible difference in terms of all tested performance domains. The AUC of the final ML model for HDP and GDM were 0.62±0.004, and 0.67±0.004, respectively.

CONCLUSIONS: The incidence of HDP and GDM in twin gestations is increasing. The predictive accuracy of the machine learning model for both HDP and GDM in twin gestations is similar to that of the logistic regression model. Both models had modest performance, well-calibrated, and neither had a poor fit. This article is protected by copyright. All rights reserved.

PMID:38805609 | DOI:10.1002/uog.27710

NEJM Evid. 2024 Apr;3(4):EVIDe2400054. doi: 10.1056/EVIDe2400054. Epub 2024 Mar 26.

NO ABSTRACT

PMID:38805605 | DOI:10.1056/EVIDe2400054

Psychiatr Pol. 2024 Apr 5:1-12. doi: 10.12740/PP/OnlineFirst/178345. Online ahead of print.

ABSTRACT

OBJECTIVES: “Schizotypy” is a term describing personality traits reflected in emotional, perceptual and cognitive styles. Affective temperaments are trait-like features which were observed to be stable in time and predispose to mood disorders. The purpose of this study was to examine relationship between schizotypal features, affective temperaments and anhedonia in patients with bipolar depression.

METHODS: 54 patients with bipolar depression were included in the study. Participant were administered the following psychometric tools: Dimensional Anhedonia Rating Scale (DARS), Snaith-Hamilton Pleasure Scale (SHAPS), Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Correlations between the variables were calculated and linear regression models were built.

RESULTS: Only hyperthymia (affective temperament) and introvertive anhedonia (schizotypal domain) were statistically significantly correlated with anhedonia. In regression models, introvertive anhedonia predicted higher whereas hyperthymic features lower severity of anhedonia (measured by the SHAPS scale).

CONCLUSIONS: Hyperthymic features are protective and introvertive anhedonia is a risk factor for consummatory anhedonia.

PMID:38805600 | DOI:10.12740/PP/OnlineFirst/178345

PLoS Comput Biol. 2024 May 28;20(5):e1011605. doi: 10.1371/journal.pcbi.1011605. Online ahead of print.

ABSTRACT

Central in the study of population codes, coordinated ensemble spiking activity is widely observable in neural recordings with hypothesized roles in robust stimulus representation, interareal communication, and learning and memory formation. Model-free measures of synchrony characterize coherent pairwise activity but not higher-order interactions, a limitation transcended by statistical models of ensemble spiking activity. However, existing model-based analyses often impose assumptions about the relevance of higher-order interactions and require repeated trials to characterize dynamics in the correlational structure of ensemble activity. To address these shortcomings, we propose an adaptive greedy filtering algorithm based on a discretized mark point-process model of ensemble spiking and a corresponding statistical inference framework to identify significant higher-order coordination. In the course of developing a precise statistical test, we show that confidence intervals can be constructed for greedily estimated parameters. We demonstrate the utility of our proposed methods on simulated neuronal assemblies. Applied to multi-electrode recordings from human and rat cortical assemblies, our proposed methods provide new insights into the dynamics underlying localized population activity during transitions between brain states.

PMID:38805569 | DOI:10.1371/journal.pcbi.1011605

PLoS Negl Trop Dis. 2024 May 28;18(5):e0012222. doi: 10.1371/journal.pntd.0012222. Online ahead of print.

ABSTRACT

Dengue poses a significant public health concern worldwide. It is identified as a recent emerging infectious disease in Nepal. Understanding the situation and dynamics between knowledge, attitudes, and practices (KAP) related to dengue among students is crucial for effective prevention and control strategies. This study aimed to assess the KAP and their associated factors of dengue among non-health undergraduate students of Nepal to identify gaps and suggest appropriate interventions. A web-based cross-sectional study was conducted among 429 non-health undergraduate students at eleven Nepalese Universities, with 80% of participants from the four most prominent ones in the country. Self-administered online forms were administered via Google Forms platform predominantly through social media for data collection. Data was cleaned and then exported to IBM SPSS Statistics 20.0 for analysis. Demographic characteristics of respondents were described using descriptive statistics. Multivariate logistic regression was conducted to determine the association between individual characteristics and KAP. Pearson’s correlation coefficient was used to determine the association between knowledge-attitude, attitude-practice, and knowledge-practice. Statistical significance was determined at the p-value < 0.05. Around half of the participants were female (50.3%). The majority of participants were between 22 to 37 years, unmarried, and belonged to the Brahmin/Chhetri ethnic group. This study demonstrated a significant gap in KAP. Only 15.2% of participants had good knowledge while 25.9% and 68.3% of participants exhibited good attitudes and practices respectively. Marital status (AOR = 3.32, CI: 1.32-8.34), third-year educational level (AOR = 3.59, CI:1.34-9.57), and fourth-year educational level (AOR = 4.93, CI:1.88-12.94) were significantly associated with knowledge regarding dengue. Age (AOR = 1.73, CI: 1.10-3.01) was significantly associated with preventive practice regarding dengue. None of the demographic or socio-economic characteristics of respondents was associated with attitude on dengue. The knowledge-attitude (rka = 0.01), knowledge-practice (rkp = 0.22), and attitude-practice (rap = 0.01) were positively correlated in this study.

PMID:38805553 | DOI:10.1371/journal.pntd.0012222