Phosphorylation of Mad1 at serine 18 by Mps1 is required for the full virulence of rice blast fungus, Magnaporthe oryzae.

The spindle assembly checkpoint (SAC) proteins are conserved among eukaryotes safeguarding chromosome segregation fidelity during mitosis. However, their biological functions in plant-pathogenic fungi remain largely unknown. In this study, we found that the SAC protein MoMad1 in rice blast fungus (Magnaporthe oryzae) localizes on the nuclear envelope and is dispensable for M. oryzae vegetative growth and tolerance to microtubule depolymerizing agent treatment. MoMad1 plays an important role in M. oryzae infection-related development and pathogenicity. The monopolar spindle 1 homologue in M. oryzae (MoMps1) interacts with MoMad1 through its N-terminal domain and phosphorylates MoMad1 at Ser-18, which is conserved within the extended N termini of Mad1s from fungal plant pathogens. This phosphorylation is required for maintaining MoMad1 protein abundance and M. oryzae full virulence. Similar to the deletion of MoMad1, treatment with Mps1-IN-1 (an Mps1 inhibitor) caused compromised appressorium formation and decreased M. oryzae virulence, and these defects were dependent on its attenuating MoMad1 Ser-18 phosphorylation. Therefore, our study indicates the function of Mad1 in rice blast fungal pathogenicity and sheds light on the potential of blocking Mad1 phosphorylation by Mps1 to control crop fungal diseases.

Knowledge and trust of mothers regarding childhood vaccination in Rwanda.

INTRODUCTION: Knowledge and trust are some of the contributing factors to vaccine acceptance(VA) and Vaccine hesitancy (VH) is one of the top threats to global health. A significant drop in childhood vaccination has been observed in recent years. One important reason that influences mothers' choice to either postpone or avoid children's vaccinations is knowledge and trust in childhood vaccines. This study aimed to assess mothers' knowledge and trust on vaccination of their children, and to examine the association between vaccination knowledge and selected socio-demographic factors. METHODS: A cross-sectional survey was conducted from January 2022 to March 2022 to assess the knowledge and trust of mothers regarding childhood vaccination. Data was collected with self-administered questionnaires. Multivariable logistic regression analysis was employed to assess factors associated with childhood vaccine knowledge and trust. RESULTS: Of the 2,126 Rwandan parents who participated in the study, the proportions with good knowledge of - and good trust in childhood vaccination were 95.5% and 91.4%, respectively. The popular sources of information about childhood vaccination were health care professionals (91.8%) and mass media (28.9%). Multinomial logistic regression analysis showed that good knowledge of - and trust in childhood vaccination were associated with the relationship with child(ren), education, occupation, and monthly income. The Multinomial logistic regression also revealed that the determinants of good knowledge of - and trust in childhood vaccination were; caregiver (p = 4.0 × 10-4, adjusted Odds Ratio (aOR); 1.7, 95%C.I; 1.3 - 2.3), no formal educational status (p = 3.3 × 10-2, aOR; 1.7, 95%C.I; 1.0 - 3.0), the unemployed occupational status (p = 2.4 × 10-2, aOR; 1.2, 95%C.I; 1.0 - 1.4), and persons on more than $401 per month (p = 2.0 × 10-4, aOR; 3.5, 95%C.I; 1.8 - 6.8). CONCLUSION: The majority of parents in Rwanda had both good knowledge of-and good trust regarding childhood vaccination. Public health strategies to promote vaccination, education programmes as well as improved communication tools between health care professionals/traditional leaders/religious leaders and parents need to be considered to achieve favourable vaccination attitudes and practices for all parents in Rwanda.

Cost-effectiveness of screening for chronic kidney disease using a cumulative eGFR-based statistic.

OBJECTIVES: Routine screening for chronic kidney disease (CKD) could enable timely interventions to slow down disease progression, but currently there are no clinical guidelines for screening. We aim to evaluate the cost-effectiveness of screening for CKD using a novel analytical tool based on a cumulative sum statistic of estimated glomerular filtration rate (CUSUMGFR). METHODS: We developed a microsimulation model that captured CKD disease progression, major complications, patients' awareness, and treatment adherence for a nationally representative synthetic cohort of age ≥ 30 years in the United States. In addition to the status quo with no screening, we considered four CUSUMGFR-based universal screening policies by frequency (annual or biennial) and starting age (30 or 60 years), and two targeted annual screening policies for patients with hypertension and diabetes, respectively. For each policy, we evaluated the total discounted disability-adjusted life years (DALYs) and direct health costs over a lifetime horizon and estimated the incremental cost-effectiveness ratio (ICER). We further performed one-way and probabilistic sensitivity analyses to assess the impact of parameter uncertainty. RESULTS: Compared with the status quo, all the CUSUMGFR-based screening policies were cost-effective under the willingness-to-pay (WTP) range of $50,000 -$100,000, with the estimated incremental cost-effectiveness ratios (ICERs) ranging from $15,614/DALYs averted to $54,373/DALYs averted. Universal annual screening with starting age of 30 was the non-dominated policy on the cost-effectiveness frontier under the WTP of approximately $25,000. Adding more recent treatment option of sodium-glucose cotransporter-2 (SGLT2) inhibitors to the treatment regimen was found to be cost-saving. Among the most influential model parameters, variation in the CKD progression rate, adherence, and testing cost resulted in the highest variability in model outcomes. CONCLUSIONS: CUSUMGFR-based screening policies for CKD are highly cost-effective in identifying patients at risk of end stage kidney disease in early stages of CKD. Given its simple requirement of a basic blood test, the CUSUMGFR-based screening can be easily incorporated into clinical workflow for disease monitoring and prevention.

Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling.

Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.

Role of electroanatomical mapping-guided superior vena cava isolation in paroxysmal atrial fibrillation patients without provoked superior vena cava triggers: a randomized controlled study.

AIMS: Data about whether empirical superior vena cava (SVC) isolation (SVCI) improves the success rate of paroxysmal atrial fibrillation (PAF) are conflicting. This study sought to first investigate the characteristics of SVC-triggered atrial fibrillation and secondly investigate the impact of electroanatomical mapping-guided SVCI, in addition to circumferential pulmonary vein isolation (CPVI), on the outcome of PAF ablation in the absence of provoked SVC triggers. METHODS AND RESULTS: A total of 130 patients undergoing PAF ablation underwent electrophysiological studies before ablation. In patients for whom SVC triggers were identified, SVCI was performed in addition to CPVI. Patients without provoked SVC triggers were randomized in a 1:1 ratio to CPVI plus SVCI or CPVI only. The primary endpoint was freedom from any documented atrial tachyarrhythmias lasting over 30 s after a 3-month blanking period without anti-arrhythmic drugs at 12 months after ablation. Superior vena cava triggers were identified in 30 (23.1%) patients with PAF. At 12 months, 93.3% of those with provoked SVC triggers who underwent CPVI plus SVCI were free from atrial tachyarrhythmias. In patients without provoked SVC triggers, SVCI, in addition to CPVI, did not increase freedom from atrial tachyarrhythmias (87.9 vs. 79.6%, log-rank P = 0.28). CONCLUSION: Electroanatomical mapping-guided SVCI, in addition to CPVI, did not increase the success rate of PAF ablation in patients who had no identifiable SVC triggers. REGISTRATION: ChineseClinicalTrials.gov: ChiCTR2000034532.

A machine learning approach to differentiate wide QRS tachycardia: distinguishing ventricular tachycardia from supraventricular tachycardia.

BACKGROUND: Differential diagnosis of wide QRS tachycardia (WQCT) has been a challenging issue. Published algorithms to distinguish ventricular tachycardia (VT) and supraventricular tachycardia (SVT) have limited diagnostic capabilities. METHODS: A total of 278 patients with WQCT from January 2010 to March 2022 were enrolled. The electrophysiological study confirmed SVT in 154 patients and VT in 65 ones. Two hundred nineteen WQCT 12-lead ECGs were randomly divided into development cohort (n = 165) and testing cohort (n = 54) data sets. The development cohort was split into a training group (n = 115) and an internal validation group (n = 50). Forty ECG features extracted from the 219 WQCT ECGs are fed into 9 iteratively trained ML algorithms. This novel ML algorithm was also compared with four published algorithms. RESULTS: In the development cohort, the Gradient Boosting Machine (GBM) model displayed the maximum area under curve (AUC) (0.91, 95% confidence interval (CI) 0.81-1.00). In the testing cohort, the GBM model had a higher AUC of 0.97 compared to 4 validated ECG algorithms, namely, Brugada (0.68), avR (0.62), RWPTII (0.72), and LLA algorithms (0.70). Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the GBM model were 0.94, 0.97, 0.90, 0.94, and 0.95, respectively. CONCLUSIONS: A GBM ML model contributes to distinguishing SVT from VT based on surface ECG features. In addition, we were able to identify important indicators for distinguishing WQCT.

Design, synthesis, and biological evaluation of novel 8-substituted quercetin derivatives targeting the ß­catenin/B-cell lymphoma 9 interaction.

The ß-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for aberrantly active Wnt/ß-catenin signaling which actively participates in initiating and progressing of many cancers. Herein, we discovered novel 8-substituted quercetin derivatives with potential inhibitory activities targeting ß-catenin/BCL9 PPI. Among all the derivatives, compound B4 displayed the most promising PPI inhibitory activity with an IC50 value of 2.25 µM in a competitive fluorescence polarization assay and a KD value of 1.44 µM for the ß-catenin protein. Furthermore, B4 selectively inhibited the growth of colorectal cancer (CRC) cells, suppressed the transactivation of Wnt signaling, and downregulated the expression of oncogenic Wnt target gene. Especially, B4 showed potent anti-CRC activity in vivo with the tumor growth inhibition (TGI) of 75.99 % and regulated the tumor immune microenvironment.

Erratum: Circulating Exosomal miR-1-3p from Rats with Myocardial Infarction Plays a Protective Effect on Contrast-Induced Nephropathy via Targeting ATG13 and activating the AKT Signaling Pathway: Erratum.

[This corrects the article DOI: 10.7150/ijbs.55887.].

FOXA1 O-GlcNAcylation-mediated transcriptional switch governs metastasis capacity in breast cancer.

FOXA1, a transcription factor involved in epigenetic reprogramming, is crucial for breast cancer progression. However, the mechanisms by which FOXA1 achieves its oncogenic functions remain elusive. Here, we demonstrate that the O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation) of FOXA1 promotes breast cancer metastasis by orchestrating the transcription of numerous metastasis regulators. O-GlcNAcylation at Thr432, Ser441, and Ser443 regulates the stability of FOXA1 and promotes its assembly with chromatin. O-GlcNAcylation shapes the FOXA1 interactome, especially triggering the recruitment of the transcriptional repressor methyl-CpG binding protein 2 and consequently stimulating FOXA1 chromatin-binding sites to switch to chromatin loci of adhesion-related genes, including EPB41L3 and COL9A2. Site-specific depletion of O-GlcNAcylation on FOXA1 affects the expression of various downstream genes and thus inhibits breast cancer proliferation and metastasis both in vitro and in vivo. Our data establish the importance of aberrant FOXA1 O-GlcNAcylation in breast cancer progression and indicate that targeting O-GlcNAcylation is a therapeutic strategy for metastatic breast cancer.

Impact of school operating scenarios on COVID-19 transmission under vaccination in the U.S.: an agent-based simulation model.

At the height of the COVID-19 pandemic, K-12 schools struggled to safely operate under the fast-changing pandemic situation. However, little is known about the impact of different school operating scenarios considering the ongoing efforts of vaccination. In this study, we deployed an agent-based simulation model to mimic disease transmission in a mid-sized community consisting of 10,000 households. A total of eight school operating scenarios were simulated, in decreasing order of restrictiveness regarding COVID-19 mitigation measures. When masks were worn at school, work, and community environments, increasing in-person education from 50% to 100% would result in only 1% increase in cumulative infections. When there were no masks nor contact tracing while schools were 100% in person, the cumulative infection increased by 86% compared to the scenario when both masking and contact tracing were in place. In the sensitivity analysis for vaccination efficacy, we found that higher vaccination efficacy was essential in reducing overall infections. Our findings showed that full in-person education was safe, especially when contact tracing, masking, and widespread vaccination were in place. If no masking nor contact tracing was practiced, the transmission would rose dramatically but eventually slow down due to herd immunity.

Perspectives and new aspects of histone deacetylase inhibitors in the therapy of CNS diseases.

Many populations worldwide are suffering from central nervous system (CNS) diseases such as brain tumors, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and Huntington's disease) and stroke. There is a shortage of effective drugs for most CNS diseases. As one of the regulatory mechanisms of epigenetics, the particular role and therapeutic benefits of histone deacetylases (HDACs) in the CNS have been extensively studied. In recent years, HDACs have attracted increasing attention as potential drug targets for CNS diseases. In this review, we summarize the recent applications of representative histone deacetylases inhibitors (HDACis) in CNS diseases and discuss the challenges in developing HDACis with different structures and better blood-brain barrier (BBB) permeability, hoping to promote the development of more effective bioactive HDACis for the treatment of CNS diseases.

Chromatin-associated OGT promotes the malignant progression of hepatocellular carcinoma by activating ZNF263.

Reversible and dynamic O-GlcNAcylation regulates vast networks of highly coordinated cellular and nuclear processes. Although dysregulation of the sole enzyme O-GlcNAc transferase (OGT) was shown to be associated with the progression of hepatocellular carcinoma (HCC), the mechanisms by which OGT controls the cis-regulatory elements in the genome and performs transcriptional functions remain unclear. Here, we demonstrate that elevated OGT levels enhance HCC proliferation and metastasis, in vitro and in vivo, by orchestrating the transcription of numerous regulators of malignancy. Diverse transcriptional regulators are recruited by OGT in HCC cells undergoing malignant progression, which shapes genome-wide OGT chromatin cis-element occupation. Furthermore, an unrecognized cooperation between ZNF263 and OGT is crucial for activating downstream transcription in HCC cells. We reveal that O-GlcNAcylation of Ser662 is responsible for the chromatin association of ZNF263 at candidate gene promoters and the OGT-facilitated HCC malignant phenotypes. Our data establish the importance of aberrant OGT activity and ZNF263 O-GlcNAcylation in the malignant progression of HCC and support the investigation of OGT as a therapeutic target for HCC.

Estimated Reductions in Opioid Overdose Deaths With Sustainment of Public Health Interventions in 4 US States.

Importance: In 2021, more than 80 000 US residents died from an opioid overdose. Public health intervention initiatives, such as the Helping to End Addiction Long-term (HEALing) Communities Study (HCS), are being launched with the goal of reducing opioid-related overdose deaths (OODs). Objective: To estimate the change in the projected number of OODs under different scenarios of the duration of sustainment of interventions, compared with the status quo. Design, Setting, and Participants: This decision analytical model simulated the opioid epidemic in the 4 states participating in the HCS (ie, Kentucky, Massachusetts, New York, and Ohio) from 2020 to 2026. Participants were a simulated population transitioning from opioid misuse to opioid use disorder (OUD), overdose, treatment, and relapse. The model was calibrated using 2015 to 2020 data from the National Survey on Drug Use and Health, the US Centers for Disease Control and Prevention, and other sources for each state. The model accounts for reduced initiation of medications for OUD (MOUDs) and increased OODs during the COVID-19 pandemic. Exposure: Increasing MOUD initiation by 2- or 5-fold, improving MOUD retention to the rates achieved in clinical trial settings, increasing naloxone distribution efforts, and furthering safe opioid prescribing. An initial 2-year duration of interventions was simulated, with potential sustainment for up to 3 additional years. Main Outcomes and Measures: Projected reduction in number of OODs under different combinations and durations of sustainment of interventions. Results: Compared with the status quo, the estimated annual reduction in OODs at the end of the second year of interventions was 13% to 17% in Kentucky, 17% to 27% in Massachusetts, 15% to 22% in New York, and 15% to 22% in Ohio. Sustaining all interventions for an additional 3 years was estimated to reduce the annual number of OODs at the end of the fifth year by 18% to 27% in Kentucky, 28% to 46% in Massachusetts, 22% to 34% in New York, and 25% to 41% in Ohio. The longer the interventions were sustained, the better the outcomes; however, these positive gains would be washed out if interventions were not sustained. Conclusions and Relevance: In this decision analytical model study of the opioid epidemic in 4 US states, sustained implementation of interventions, including increased delivery of MOUDs and naloxone supply, was found to be needed to reduce OODs and prevent deaths from increasing again.

Delay from Screening to Diagnosis in Autism Spectrum Disorder: Results from a Large National Health Research Network.

To examine delay from developmental screening to autism diagnosis, we used real-world health care data from a national research network to estimate the time between these events. We found an average delay of longer than 2 years from first screening to diagnosis, with no significant differences observed by sex, race, or ethnicity.

Half versus normal saline irrigation during catheter ablation of outflow tract ventricular arrhythmias (HALF): a multi-center, parallel, open-label, randomized controlled study.

BACKGROUND: Animal studies demonstrated that deeper lesions could be achieved during radio-frequency catheter ablation (RFCA) by using half saline (HS) compared to normal saline (NS) as irrigation. OBJECTIVES: This study sought to compare the efficiency and safety of HS and NS for irrigation during RFCA of idiopathic outflow tract ventricular arrhythmia (OT-VA). METHODS: In this multicenter, randomized controlled study, 167 patients undergoing RFCA of OT-VA were randomized 1:1 to receive HS- or NS-irrigated ablation. Acute success was defined as the absence of induced targeted premature ventricular contraction (PVC) at the end of the procedure. The 6-month success was defined as a ≥ 80% reduction of pre-procedural PVC burden. RESULTS: There were no differences of baseline characteristics between the HS and NS group. Patients in HS group had shorter total ablation time (259.5 ± 155.5 S vs. 355.6 ± 230.7 S, P = 0.04) than that in NS group. The acute and 6-month success rates were similar between the HS and NS group (92.8 vs. 91.7%, P = 0.79; 90.9 vs. 92.1%, P = 0.79, respectively). No significant difference was observed in the incidence of steam pops between the HS and NS group (2.4 vs. 1.2%, P = 0.62). CONCLUSIONS: The ablation using HS irrigation achieved similar success rate and safety compared to that using NS irrigation but was associated with a shorter total ablation time. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059205).

O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance.

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O-GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O-GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O-GlcNAcylation-modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O-GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O-GlcNAcylation in cancer therapy.

A scoping review of the opioid epidemic among U.S. Immigrants: Implications for treatment practices.

The purpose of this review was to identify knowledge gaps within the literature regarding the impact of opioid use disorder, specific to immigrants in the United States, by addressing the following questions: 1) What is presented in the literature about the impact of opioid use disorder (OUD) and the opioid epidemic on immigrants in the United States?; and 2) What role does culture play in the opioid use disorder experiences of immigrants in the United States? Nineteen research articles were uncovered that addressed immigrants in the U.S. and opioid use disorder. The following themes prevailed: 1) OUD comparisons, 2) OUD comorbidities, 3) disparate OUD treatment engagement, and 4) the role of country of origin. Limited review findings support the need for future research on the topic of opioid misuse among immigrants in the United States. The authors elaborated on additional issues that influence OUD rates and warrant further exploration. Matters related to the potential positive roles of religion and faith leaders, cultural perceptions and expectations about gender roles, immigration status, ethnically diverse needs among sub-groups of immigrants, the role of geographic location within the U.S., and the implications of COVID-19 on OUD among immigrants need to be addressed to alleviate the deleterious impact of opioid misuse among immigrants.

Discovery of Novel 3-Phenylpiperidine Derivatives Targeting the ß-Catenin/B-Cell Lymphoma 9 Interaction as a Single Agent and in Combination with the Anti-PD-1 Antibody for the Treatment of Colorectal Cancer.

Direct disruption of the ß-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential strategy for colorectal cancer (CRC) treatment through inhibiting oncogenic Wnt activity. Herein, a series of 3-phenylpiperidine derivatives were synthesized and evaluated as ß-catenin/BCL9 PPI inhibitors. Among them, compound 41 showed the best IC50 (0.72 µM) in a competitive fluorescence polarization assay and a KD value of 0.26 µM for the ß-catenin protein. This compound selectively inhibited the growth of CRC cells, suppressed Wnt signaling transactivation, and downregulated oncogenic Wnt target gene expression. In vivo, 41 showed potent anti-CRC activity and promoted the infiltration and function of cytotoxic T lymphocytes while decreasing the infiltration of regulatory T-cells (Tregs). Furthermore, the combination of 41 and the anti-PD-1 antibody (Ab) efficiently enhanced anti-CRC efficacy, first verifying the in vivo efficacy of the small-molecule ß-catenin/BCL9 PPI inhibitor and anti-PD-1 Ab in combination.

Longitudinal transitions in tobacco use in youth and young adults: A latent transition analysis of the population assessment of tobacco and health study from Wave 1 to 5.

BACKGROUND: Tobacco use by youth and young adults can lead to significant long-term health problems. We aim to understand transitions in tobacco use patterns among these groups and the factors that affect transition patterns. METHODS: Using the five waves of data from the nationally representative Population Assessment of Tobacco and Health (PATH) Study (2013-2019), we conducted latent class analysis and latent transition analysis to understand tobacco use classes and the longitudinal transitions between classes. We also adjusted for covariates, including demographics, individual behaviors, household environment, and psychosocial factors, to capture their effects on class transition probabilities. RESULTS: Three tobacco use behaviors were identified: non-current user (C1), moderate e-cigarette user (C2), and poly-tobacco user (C3). At baseline (Wave 1), 94.4% of participants were classified as C1, 3.2% as C2, and 2.4% as C3, and the distribution shifted towards C2 and C3 over time. Progression to the next class represented the most common transitions (14.1% C2 to C3, 10.7% C1 to C2), while the direct progression from C1 to C3 was rare (0.6%). Being male, White, adult, living in smoking-allowed households, past-year alcohol use, drug use, internalizing problems, and social media follower of tobacco brands were associated with a faster progression to poly-tobacco use. CONCLUSIONS: The transition patterns implied that e-cigarette use might be an intermediate progression from non-current use into poly-tobacco use. Individual behaviors, household environment, and psychosocial factors are associated with elevated risks of progression. The findings may inform tobacco prevention and cessation policies among youth and young adults.

Disability-Adjusted Life-Years for Drug Overdose Crisis and COVID-19 Are Comparable During the Two Years of Pandemic in the United States.

OBJECTIVES: The drug overdose crisis with shifting patterns from primarily opioid to polysubstance uses and COVID-19 infections are 2 concurrent public health crises in the United States, affecting the population of sizes in different magnitudes (approximately < 10 million for substance use disorder [SUD] and drug overdoses vs 80 million for COVID-19 within 2 years of the pandemic). Our objective is to compare the relative scale of disease burden for the 2 crises within a common framework, which could help inform policy makers with resource allocation and prioritization strategies. METHODS: We calculated disability-adjusted life-years (DALYs) for SUD (including opioids and stimulants) and COVID-19 infections, respectively. We collected estimates for SUD prevalence, overdose deaths, COVID-19 cases and deaths, disability weights, and life expectancy from multiple publicly available sources. We then compared age distributions of estimated DALYs. RESULTS: We estimated a total burden of 13.83 million DALYs for SUD and drug overdoses and 15.03 million DALYs for COVID-19 in 2 years since March 2020. COVID-19 burden was dominated by the fatal burden (> 95% of total DALYs), whereas SUD burden was attributed to both fatal (53%) and nonfatal burdens (47%). The highest disease burden was among individuals aged 30 to 39 years for SUD (27%) and 50 to 64 years for COVID-19 (31%). CONCLUSIONS: Despite the smaller size of the affected population, SUD and drug overdoses resulted in comparable disease burden with the COVID-19 pandemic. Additional resources supporting evidence-based interventions in prevention and treatment may be warranted to ameliorate SUD and drug overdoses during both the pandemic and postpandemic recovery.