Category: Statistics

PLoS One. 2023 Dec 28;18(12):e0296054. doi: 10.1371/journal.pone.0296054. eCollection 2023.

ABSTRACT

BACKGROUND: The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP.

METHODS: Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model.

RESULTS: Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11-0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82-4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60-2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46-11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81-2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance.

CONCLUSIONS: The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

PMID:38153953 | DOI:10.1371/journal.pone.0296054

PLoS Genet. 2023 Dec 28;19(12):e1011104. doi: 10.1371/journal.pgen.1011104. Online ahead of print.

ABSTRACT

Identifying causal variants from genome-wide association studies (GWAS) is challenging due to widespread linkage disequilibrium (LD) and the possible existence of multiple causal variants in the same genomic locus. Functional annotations of the genome may help to prioritize variants that are biologically relevant and thus improve fine-mapping of GWAS results. Classical fine-mapping methods conducting an exhaustive search of variant-level causal configurations have a high computational cost, especially when the underlying genetic architecture and LD patterns are complex. SuSiE provided an iterative Bayesian stepwise selection algorithm for efficient fine-mapping. In this work, we build connections between SuSiE and a paired mean field variational inference algorithm through the implementation of a sparse projection, and propose effective strategies for estimating hyperparameters and summarizing posterior probabilities. Moreover, we incorporate functional annotations into fine-mapping by jointly estimating enrichment weights to derive functionally-informed priors. We evaluate the performance of SparsePro through extensive simulations using resources from the UK Biobank. Compared to state-of-the-art methods, SparsePro achieved improved power for fine-mapping with reduced computation time. We demonstrate the utility of SparsePro through fine-mapping of five functional biomarkers of clinically relevant phenotypes. In summary, we have developed an efficient fine-mapping method for integrating summary statistics and functional annotations. Our method can have wide utility in understanding the genetics of complex traits and increasing the yield of functional follow-up studies of GWAS. SparsePro software is available on GitHub at https://github.com/zhwm/SparsePro.

PMID:38153934 | DOI:10.1371/journal.pgen.1011104

Syst Biol. 2023 Dec 28:syad075. doi: 10.1093/sysbio/syad075. Online ahead of print.

ABSTRACT

Birth-death models are stochastic processes describing speciation and extinction through time and across taxa, and are widely used in biology for inference of evolutionary timescales. Previous research has highlighted how the expected trees under the constant-rate birth-death (crBD) model tend to differ from empirical trees, for example with respect to the amount of phylogenetic imbalance. However, our understanding of how trees differ between the crBD model and the signal in empirical data remains incomplete. In this Point of View, we aim to expose the degree to which the crBD model differs from empirically inferred phylogenies and test the limits of the model in practice. Using a wide range of topology indices to compare crBD expectations against a comprehensive dataset of 1189 empirically estimated trees, we confirm that crBD model trees frequently differ topologically compared with empirical trees. To place this in the context of standard practice in the field, we conducted a meta-analysis for a subset of the empirical studies. When comparing studies that used Bayesian methods and crBD priors with those that used other non-crBD priors and non-Bayesian methods (i.e., maximum likelihood methods), we do not find any significant differences in tree topology inferences. To scrutinize this finding for the case of highly imbalanced trees, we selected the 100 trees with the greatest imbalance from our dataset, simulated sequence data for these tree topologies under various evolutionary rates, and re-inferred the trees under maximum likelihood and using the crBD model in a Bayesian setting. We find that when the substitution rate is low, the crBD prior results in overly balanced trees, but the tendency is negligible when substitution rates are sufficiently high. Overall, our findings demonstrate the general robustness of crBD priors across a broad range of phylogenetic inference scenarios, but also highlights that empirically observed phylogenetic imbalance is highly improbable under the crBD model, leading to systematic bias in data sets with limited information content.

PMID:38153910 | DOI:10.1093/sysbio/syad075

PLOS Glob Public Health. 2023 Dec 28;3(12):e0001984. doi: 10.1371/journal.pgph.0001984. eCollection 2023.

ABSTRACT

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings. The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother. The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks’ gestation. Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants’ development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively. Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04). The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

PMID:38153909 | DOI:10.1371/journal.pgph.0001984

ACS Appl Mater Interfaces. 2023 Dec 28. doi: 10.1021/acsami.3c14246. Online ahead of print.

ABSTRACT

Opioids are considered to be a global threat, and we are facing the worst opioid crisis of the decade. Synthetic opioids like fentanyl are highly potent and deadly toward human body, and hence its detection is an inevitable requirement globally. Naloxone is known for its antagonist property toward fentanyl, and we performed computational simulations to find their interactions and use this principle to build the first of a kind impedimetric sensor device, transduced by 3D-ZIF-8 with in situ encapsulated naloxone-gold nanoparticles. The probe is synthesized using a unique encapsulation strategy, thoroughly characterized by various physicochemical and microscopic tools. The sensor is highly selective toward fentanyl and can detect fentanyl up to 100 ppm in a synthetic sample. A prototype device is also built based on the synthetic calibration and applied to the spiked urine sample, and the performance is evaluated using statistical and machine learning tools.

PMID:38153905 | DOI:10.1021/acsami.3c14246

Vestn Otorinolaringol. 2023;88(6):42-47. doi: 10.17116/otorino20238806142.

ABSTRACT

OBJECTIVE: The study of the population and subpopulation content of lymphocytes and immunoglobulins and their associations in IgE-mediated CRS relative to other CRS and the control group.

MATERIAL AND METHODS: 23 patients with IgE-mediated chronic rhinusinusitis and 67 patients with normal IgE blood levels were examined. For analysis, flow cytometry (Cytomics FC500, Beckman Coulter, USA), using monoclonal antibodies CD3⁺, CD4⁺, CD8⁺, CD16⁺, CD19⁺ and enzyme immunoassay (Thermo Scientific Multiskan FC, Thermo Fisher Scientific, USA), using IgA, IgM, IgE and IgG in serum, statistical processing was performed using Statistica 7.0.

RESULTS: In patients with CRS and IgE-mediated CRS, hyperactivation was revealed in both T- and B-cell immunity, manifested by an increase in the level of T-lymphocytes, NK-lymphocytes and B-lymphocytes. More pronounced disorders in the immune status are detected in patients with IgE – mediated CRS, there is a more pronounced activation of the T-cell immune link due to an increase in T-helper cells, T-killer/suppressor cells, an imbalance in their number is accompanied by a decrease in their ratio in the immunoregulatory index. Activation of the immune system in patients with CRS is also associated with an increase in the content of mature B-lymphocytes (CD19⁺), while only in patients with IgE-mediated CRS, hypergammaglobulinemia of classes A and M was detected.

CONCLUSION: Changes in the immune status indicate a violation of immune regulation, confirmed by the revealed correlations between the subpopulations of lymphocytes and immunoglobulins that implement the immune response in this condition. The greatest number of violations in the regulation is associated with mature T-lymphocytes in both CRS and IgE-mediated CRS, while only IgA fully retains its function.

PMID:38153892 | DOI:10.17116/otorino20238806142

Vestn Otorinolaringol. 2023;88(6):30-37. doi: 10.17116/otorino20238806130.

ABSTRACT

OBJECTIVE: To evaluate the features of voice disorders associated with novel coronavirus infection and to develop the clinical algorithm for diagnostic and treatment these patients.

MATERIAL AND METHODS: A prospective observational study was conducted in patients with dysphonia after COVID-19 (n=60). All patients underwent a comprehensive voice assessment before and after the proposed treatment. The follow-up period was 1 month.

RESULTS: Functional dysphonia or aphonia with a stable (refractory) or recurrent course was diagnosed in 58 (97%) patients. A tendency to an increase in the value of the latent period of the P300 and MMN in patients with voice disorder was revealed. There was a significant decrease in supraglottic constriction and glottal insufficiency before and after the treatment. The mean VHI-10 decreased from 25.4 before treatment to 15.3 after treatment. The DSI which is based on the set of voice measurements, statistically significant improved from -5.2 to 2.6 in patients as a result of treatment. The average value of MFI-20 improved from 65.4 (8.7) at the beginning of the study to 20.3 (5.3) after treatment.

CONCLUSION: In patients with dysphonia or aphonia associated with COVID-19 are indicated a refractory type of dysphonia. This was indicated by the study of AEPs of the brain. The clinical algorithm for treatment and diagnostic patients with voice disorders after COVID-19 has been developed. The treatment of this group of patients should be adjunct by the drug therapy, kinesiotaping method and psychotherapy.

PMID:38153890 | DOI:10.17116/otorino20238806130

J Magn Reson Imaging. 2023 Dec 28. doi: 10.1002/jmri.29208. Online ahead of print.

ABSTRACT

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been developed for assessing bladder cancer from multiparametric (mp) MRI but its performance in diagnosing muscle-invasive bladder cancer (MIBC) is suboptimal.

PURPOSE: To investigate associations between normalized apparent diffusion coefficient (NADC) and clinicopathological characteristics and to determine whether the inclusion of NADC can improve the performance of VI-RADS in diagnosing MIBC.

STUDY TYPE: Retrospective.

POPULATION: Two hundred seventy-five patients with pathologically confirmed bladder cancer (101 MIBC and 174 non-MIBC [NMIBC]) underwent preoperative mpMRI (233 male, 42 female).

FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (free-breathing spin-echo), and dynamic contrast-enhanced imaging (gradient-echo).

ASSESSMENT: NADC was the mean ADC of tumor divided by that of the iliopsoas muscles in trans caput femoris plane. Associations between NADC and clinicopathological characteristics were evaluated. Models were established for differentiating MIBC and NMIBC: VI-RADS model; VN model (VI-RADS and NADC), Images model (significant variables from imaging associated with MIBC), LN model (Images model without NADC), and Full model (all significant variables associated with MIBC).

STATISTICAL TESTS: Variables for model development were based on logistic regression. Models were evaluated by receiver operating characteristic (ROC) curve. Comparison of the area under the curves (AUCs) for the models used DeLong’s test. A P value <0.05 was considered statistically significant.

RESULTS: NADC was significantly lower in lesions with diameter ≥ 3 cm, MIBC, histological high grade, lymph node metastasis, and lymphovascular invasion. Compared with VI-RADS model, the AUCs for VN model (VI-RADS score and NADC), Images model (VI-RADS score, NADC and tumor size) and Full model (VI-RADS score, NADC, tumor size and histological grade) were significantly higher. No significant differences were observed between the AUCs for VN model and Images model (P = 0.051).

DATA CONCLUSION: NADC reflects information about the aggressiveness of bladder cancer. Combining VI-RADS with NADC can improve performance in diagnosing MIBC.

EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

PMID:38153874 | DOI:10.1002/jmri.29208

J Manag Care Spec Pharm. 2024 Jan;30(1):43-51. doi: 10.18553/jmcp.2024.30.1.43.

ABSTRACT

BACKGROUND: Improving medication adherence remains an important goal to improve therapeutic outcomes and lower health care costs. Point-of-sale prescription costs and forgetfulness remain top reasons why patients do not adhere to medications. Programs using both text message-based reminders and financial incentives may encourage patients to refill their prescriptions on time by reducing copays through discounts at the point of sale. Sempre Health, the subject of our analysis, provides both text message refill reminders and a dynamic discount incentive program to improve medication adherence.

OBJECTIVE: To evaluate the impact of a financial incentive/refill reminder program on medication adherence and total cost of care for patients taking the antithrombotic agents ticagrelor, apixaban, or rivaroxaban in a large regional health plan.

METHODS: After propensity-score matching on demographics, socioeconomic status, baseline copay, prior pharmacy/medical spend, and morbidity, we compared-using a difference-in-differences analytic approach-adherence (measured by proportion of days covered), unplanned health care utilization, and costs (total cost of care, medical, and pharmacy cost) of health plan members who did and did not enroll in the financial incentive/refill reminder program between February 1, 2019, and October 31, 2021, over 1 and 2 years. Because of differences in patient characteristics, we analyzed patients on ticagrelor (the antiplatelet group), apixaban, and rivaroxaban (the anticoagulant group) separately.

RESULTS: There were a total of 1,292 one-to-one program and control propensity-matched patients: 166 each for the antiplatelet group and 480 each for the anticoagulant group. The average age of the anticoagulant group was 62 years; more than 60% were male, and approximately 45% had no prior unplanned care events. In contrast, the average age of the antiplatelet group was 57 years; more than 70% were male, and approximately 21% had no prior unplanned care events. In the antiplatelet group, the proportions adherent (proportion of days covered ≥80%) were 63.3% vs 42.8% (P = 0.0002) for program vs controls. Similarly, in the anticoagulant group, the proportion adherent was 77.9% vs 60.2% (P < 0.0001) for program vs controls. Reflecting improved adherence, costs of apixaban and rivaroxaban increased by $79 per member per month (PMPM) (P < 0.0001), with no statistically significant differences in other costs. Similarly, the cost of ticagrelor increased by $77 PMPM (P = 0.0102) with no statistically significant differences in other costs. Finally, there was a 16% (P = 0.032) reduction in emergency department use for those in the program.

CONCLUSIONS: The financial incentive and refill reminder program was associated with improved adherence to antithrombotic medications, reduced emergency department use, and increased medication costs, but not in total pharmacy, medical, or total cost of care in both subgroups.

PMID:38153862 | DOI:10.18553/jmcp.2024.30.1.43

J Magn Reson Imaging. 2023 Dec 28. doi: 10.1002/jmri.29186. Online ahead of print.

ABSTRACT

BACKGROUND: TP53 mutations are associated with prostate cancer (PCa) prognosis and therapy.

PURPOSE: To develop TP53 mutation classification models for PCa using MRI radiomics and clinicopathological features.

STUDY TYPE: Retrospective.

POPULATION: 388 patients with PCa from two centers (Center 1: 281 patients; Center 2: 107 patients). Cases from Center 1 were randomly divided into training and internal validation sets (7:3). Cases from Center 2 were used for external validation.

FIELD STRENGTH/SEQUENCE: 3.0T/T2-weighted imaging, dynamic contrast-enhanced imaging, diffusion-weighted imaging.

ASSESSMENT: Each patient’s index tumor lesion was manually delineated on the above MRI images. Five clinicopathological and 428 radiomics features were obtained from each lesion. Radiomics features were selected by least absolute shrinkage and selection operator and binary logistic regression (LR) analysis, while clinicopathological features were selected using Mann-Whitney U test. Radiomics models were constructed using LR, support vector machine (SVM), and random forest (RF) classifiers. Clinicopathological-radiomics combined models were constructed using the selected radiomics and clinicopathological features with the aforementioned classifiers.

STATISTICAL TESTS: Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). P value <0.05 indicates statistically significant.

RESULTS: In the internal validation set, the radiomics model had an AUC of 0.74 with the RF classifier, which was significantly higher than LR (AUC = 0.61), but similar to SVM (AUC = 0.69; P = 0.422). For the combined model, the AUC of RF model was 0.84, which was significantly higher than LR (0.64), but similar to SVM (0.80; P = 0.548). Both the combined RF and combined SVM models showed significantly higher AUCs than the radiomics models. In the external validation set, the combined RF and combined SVM models showed AUCs of 0.83 and 0.82.

DATA CONCLUSION: Pathological-radiomics combined models with RF, SVM show the association of TP53 mutations and pathological-radiomics features of PCa.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:38153859 | DOI:10.1002/jmri.29186