The tobacco quitline setting as a teachable moment: The Educating Quitline Users About Lung (EQUAL) cancer screening randomized trial.

Although lung cancer screening (LCS) using low-dose CT is recommended for high-risk individuals, screening adherence remains low. We conducted a randomized trial to compare two methods of providing LCS education to Maryland Tobacco Quitline (MTQ) callers in order to assess whether this setting may serve as a teachable moment for LCS-eligible individuals. MTQ callers (50-80 years, 20+ pack-years, prior LCS ≥12 months) completed the baseline and were randomized to the Print- or Web-based version of ShouldIScreen.com. Participants completed 1- and 4-month follow-up assessments to evaluate intervention engagement and LCS-related outcomes. Participants (Print = 152, Web = 146) were 61.7 (SD = 6.3) years old and reported 63.5 pack-years (SD = 36.0). Most identified as Black (54.2%), female (66.1%), having internet access (78.9%), completing other recommended cancer screenings (86.3%), and that they would undergo LCS if recommended by their provider (91.3%). By 4 months, significantly more Print (75.0%) than Web (61.6%) participants had read the materials (P = .01). Most reported the interventions contained "the right amount" of information (92.6%) and prepared them to talk with their doctor (57.2%). Regarding screening-related outcomes, 42.8% (Print) and 43.8% (Web) had scheduled or completed a low-dose CT scan or a shared decision-making visit (P = .86). In a racially diverse sample of LCS-eligible quitline callers, offering LCS educational materials resulted in high intervention engagement and screening-related appointments. As >20% did not have internet access, providing participants' preferred modality (web/print) may improve intervention engagement and knowledge. Improving LCS awareness represents an important opportunity to increase screening among eligible but unscreened quitline callers.

Although annual lung cancer screening (LCS) using low-dose CT is recommended for high-risk individuals, screening adherence remains low. In partnership with the Maryland Tobacco Quitline (MTQ), we compared Print (N = 152) versus Web (N = 146) methods for educating quitline callers about LCS. MTQ callers (50­80 years, 20+ pack-years) completed the baseline and the 1- and 4-month follow-up assessments to evaluate intervention engagement and LCS-related outcomes. Over half of participants identified as Black (54.4%), female (66.2%), and reported having internet access (78.9%), completing other recommended cancer screenings (86%), and would undergo LCS if recommended by their provider (91%). Significantly more Print (75.0%) than Web (61.9%) participants read the materials. Half of participants reported the interventions prepared them to talk with their doctor (57.4%). Regarding screening-related outcomes, 42.8% (Print) and 43.8% (Web) had scheduled or completed a CT scan or a shared decision-making visit. In a racially diverse sample of LCS-eligible quitline callers, offering LCS educational materials resulted in high intervention engagement and screening-related appointments. As >20% did not have internet access, offering the preferred intervention modality may result in improved intervention engagement and knowledge. Effectively improving awareness represents an opportunity to increase screening among LCS-eligible quitline callers.

Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objectives: To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and applied it to EHR data in the N3C (January 1, 2018-April 7, 2022). HIPPS combines: (1) an extension of a previously published pregnancy episode algorithm, (2) a novel algorithm to detect gestational age-specific signatures of a progressing pregnancy for further episode support, and (3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated pregnancy cohorts based on gestational age precision and pregnancy outcomes for assessment of accuracy and comparison of COVID-19 and other characteristics. Results: We identified 628 165 pregnant persons with 816 471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, abortions), and 23.3% had unknown outcomes. Clinician validation agreed 98.8% with HIPPS-identified episodes. We were able to estimate start dates within 1 week of precision for 475 433 (58.2%) episodes. 62 540 (7.7%) episodes had incident COVID-19 during pregnancy. Discussion: HIPPS provides measures of support for pregnancy-related variables such as gestational age and pregnancy outcomes based on N3C data. Gestational age precision allows researchers to find time to events with reasonable confidence. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational age that addresses data inconsistency and missingness in EHR data.

ALDH2 polymorphism, alcohol intake and the attributable burden of cancer in East Asia: systematic review, meta-analysis, and modeling study.

PURPOSE: To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure. METHODS: We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease (GBD) modeling framework was applied to estimate the population attributable fraction, incidence, and disability-adjusted life-years (DALYs) lost to alcohol-attributable cancer. RESULTS: We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, esophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually were underestimated by 1.20 million. CONCLUSIONS: The burden of liver, esophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.

Ionizable Lipid with Supramolecular Chemistry Features for RNA Delivery In Vivo.

Lipid nanoparticles (LNPs) and ribonucleic acid (RNA) technology are highly versatile tools that can be deployed for diagnostic, prophylactic, and therapeutic applications. In this report, supramolecular chemistry concepts are incorporated into the rational design of a new ionizable lipid, C3-K2-E14, for systemic administration. This lipid incorporates a cone-shaped structure intended to facilitate cell bilayer disruption, and three tertiary amines to improve RNA binding. Additionally, hydroxyl and amide motifs are incorporated to further enhance RNA binding and improve LNP stability. Optimization of messenger RNA (mRNA) and small interfering RNA (siRNA) formulation conditions and lipid ratios produce LNPs with favorable diameter (<150 nm), polydispersity index (<0.15), and RNA encapsulation efficiency (>90%), all of which are preserved after 2 months at 4 or 37 °C storage in ready-to-use liquid form. The lipid and formulated LNPs are well-tolerated in animals and show no deleterious material-induced effects. Furthermore, 1 week after intravenous LNP administration, fluorescent signal from tagged RNA payloads are not detected. To demonstrate the long-term treatment potential for chronic diseases, repeated dosing of C3-K2-E14 LNPs containing siRNA that silences the colony stimulating factor-1 (CSF-1) gene can modulate leukocyte populations in vivo, further highlighting utility.

Improving Knowledge About Pregnancy for Deaf South African Women of Reproductive Age Through a Text Messaging-Based Information Campaign: Mixed Methods Study.

BACKGROUND: Signing Deaf South Africans have limited access to health information and, consequently, limited knowledge about health. Maternal and neonatal mortality rates are high. Cell phone use is high, making it a potentially effective way of communicating about maternal and child health. OBJECTIVE: The primary aim of this study was to assess whether an SMS text messaging-based health information campaign could improve knowledge about pregnancy, antenatal care, and healthy living during pregnancy for signing Deaf South African women of reproductive age. The secondary aim was to evaluate the acceptability of such an intervention. METHODS: This study was designed as a pretest-posttest study. A baseline questionnaire assessed participants' knowledge about pregnancy, antenatal care, and healthy living during pregnancy before an SMS text messaging-based information campaign was conducted. After the campaign, an exit questionnaire was administered containing the same questions as the baseline questionnaire with additional questions on general acceptability and communication preferences. The results were compared between baseline and exit using the McNemar and Wilcoxon signed rank tests. A focus group aimed to obtain further information on the impact and acceptability of SMS text messages. The focus group was analyzed inductively. RESULTS: The study showed a statistically significant improvement in overall health knowledge among participants. Despite this, some participants found the medical terminology challenging to understand. Several ways of improving SMS text messaging campaigns for the Deaf were identified, including using Multimedia Messaging Services with a person signing messages and linking information campaigns to a communication service that would enable Deaf people to pose questions. The focus group also suggested that SMS text messages might play a role in motivating healthy behaviors during pregnancy. CONCLUSIONS: The SMS text messaging campaign effectively improved Deaf women's knowledge about pregnancy, antenatal care, and healthy living during pregnancy and has the potential to affect health behavior. This contrasts with a similar study on hearing pregnant women. This suggests that SMS text messages may be particularly effective in improving Deaf people's health knowledge. However, attention should be paid to Deaf participants' specific needs and communication preferences to optimize impact. The potential of using SMS text messaging campaigns to affect behavior should be studied. TRIAL REGISTRATION: Pan-African Clinical Trials Registry (PACTR) PACTR201512001352180; https://tinyurl.com/3rxvsrbe.

The city-wide full-scale interactive application of sewage surveillance programme for assisting real-time COVID-19 pandemic control - A case study in Hong Kong.

The paper discusses the implementation of Hong Kong's tailor-made sewage surveillance programme led by the Government, which has demonstrated how an efficient and well-organized sewage surveillance system can complement conventional epidemiological surveillance to facilitate the planning of intervention strategies and actions for combating COVID-19 pandemic in real-time. This included the setting up of a comprehensive sewerage network-based SARS-CoV-2 virus surveillance programme with 154 stationary sites covering 6 million people (or 80 % of the total population), and employing an intensive monitoring programme to take samples from each stationary site every 2 days. From 1 January to 22 May 2022, the daily confirmed case count started with 17 cases per day on 1 January to a maximum of 76,991 cases on 3 March and dropped to 237 cases on 22 May. During this period, a total of 270 "Restriction-Testing Declaration" (RTD) operations at high-risk residential areas were conducted based on the sewage virus testing results, where over 26,500 confirmed cases were detected with a majority being asymptomatic. In addition, Compulsory Testing Notices (CTN) were issued to residents, and the distribution of Rapid Antigen Test kits was adopted as alternatives to RTD operations in areas of moderate risk. These measures formulated a tiered and cost-effective approach to combat the disease in the local setting. Some ongoing and future enhancement efforts to improve efficacy are discussed from the perspective of wastewater-based epidemiology. Forecast models on case counts based on sewage virus testing results were also developed with R2 of 0.9669-0.9775, which estimated that up to 22 May 2022, around 2,000,000 people (~67 % higher than the total number of 1,200,000 reported to the health authority, due to various constraints or limitations) had potentially contracted the disease, which is believed to be reflecting the real situation occurring in a highly urbanized metropolis like Hong Kong.

Cyclin A-CDK1 suppresses the expression of the CDK1 activator CDC25A to safeguard timely mitotic entry.

Cyclin A and CDC25A are both activators of cyclin-dependent kinases (CDKs): cyclin A acts as an activating subunit of CDKs and CDC25A a phosphatase of the inhibitory phosphorylation sites of the CDKs. In this study, we uncovered an inverse relationship between the two CDK activators. As cyclin A is an essential gene, we generated a conditional silencing cell line using a combination of CRISPR-Cas9 and degron-tagged cyclin A. Destruction of cyclin A promoted an acute accumulation of CDC25A. The increase of CDC25A after cyclin A depletion occurred throughout the cell cycle and was independent on cell cycle delay caused by cyclin A deficiency. Moreover, we determined that the inverse relationship with cyclin A was specific for CDC25A and not for other CDC25 family members or kinases that regulate the same sites in CDKs. Unexpectedly, the upregulation of CDC25A was mainly caused by an increase in transcriptional activity instead of a change in the stability of the protein. Reversing the accumulation of CDC25A severely delayed G2-M in cyclin A-depleted cells. Taken together, these data provide evidence of a compensatory mechanism involving CDC25A that ensures timely mitotic entry at different levels of cyclin A.

Iterative Design of Ionizable Lipids for Intramuscular mRNA Delivery.

Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicles for RNA and have enabled the development of RNA-based drugs such as the mRNA COVID-19 vaccines. Functional delivery of mRNA by an LNP greatly depends on the inclusion of an ionizable lipid, and small changes to these lipid structures can significantly improve delivery. However, the structure-function relationships between ionizable lipids and mRNA delivery are poorly understood, especially for LNPs administered intramuscularly. Here, we show that the iterative design of a novel series of ionizable lipids generates key structure-activity relationships and enables the optimization of chemically distinct lipids with efficacy that is on-par with the current state of the art. We find that the combination of ionizable lipids comprising an ethanolamine core and LNPs with an apparent pKa between 6.6 and 6.9 maximizes intramuscular mRNA delivery. Furthermore, we report a nonlinear relationship between the lipid-to-mRNA mass ratio and protein expression, suggesting that a critical mass ratio exists for LNPs and may depend on ionizable lipid structure. Our findings add to the mechanistic understanding of ionizable lipids and demonstrate that hydrogen bonding, ionization behavior, and lipid-to-mRNA mass ratio are key design parameters affecting intramuscular mRNA delivery. We validate these insights by applying them to the rational design of new ionizable lipids. Overall, our iterative design strategy efficiently generates potent ionizable lipids. This hypothesis-driven method reveals structure-activity relationships that lay the foundation for the optimization of ionizable lipids in future LNP-RNA drugs. We foresee that this design strategy can be extended to other optimization parameters beyond intramuscular expression.

Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study.

BACKGROUND: In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. METHODS: This is a retrospective cohort study comprising late preterm deliveries (4,341 mother-child pairs) within the Mount Sinai Health System, 2012-2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. RESULTS: Among a total of 4,341 mother-child pairs (3,309 singleton and 1,032 twin mother-child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31-0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34-2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11-1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12-4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12-0.82], p = 0.02). CONCLUSIONS: Exposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

The engineering challenges and opportunities when designing potent ionizable materials for the delivery of ribonucleic acids.

INTRODUCTION: Ionizable lipids are critical components in lipid nanoparticles. These molecules sequester nucleic acids for delivery to cells. However, to build more efficacious delivery molecules, the field must continue to broaden structure-function studies for greater insight. While nucleic acid-binding efficiency, degradability and nanoparticle stability are vitally important, this review offers perspective on additional factors that must be addressed to improve delivery efficiency. AREAS COVERED: We discuss how administration route, cellular heterogeneity, uptake pathway, endosomal escape timing, age, sex, and threshold effects can change depending on the type of LNP ionizable lipid. EXPERT OPINION: Ionizable lipid structure-function studies often focus on the efficiency of RNA utilization and biodistribution. While these focus areas are critical, they remain high-level observations. As our tools for observation and system interrogation improve, we believe that the field should begin collecting additional data. At the cellular level, this data should include age (dividing or senescent cells), sex and phenotype, cell entry pathway, and endosome type. Additionally, administration route and dose are essential to track. This additional data will allow us to identify and understand heterogeneity in LNP efficacy across patient populations, which will help us provide better ionizable lipid options for different groups.

Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objective: To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named H ierarchy and rule-based pregnancy episode I nference integrated with P regnancy P rogression S ignatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results: We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion: HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.

Improving preeclampsia risk prediction by modeling pregnancy trajectories from routinely collected electronic medical record data.

Preeclampsia is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to reduce the risk of adverse outcomes. We assessed whether information routinely collected in electronic medical records (EMR) could enhance the prediction of preeclampsia risk beyond what is achieved in standard of care assessments. We developed a digital phenotyping algorithm to curate 108,557 pregnancies from EMRs across the Mount Sinai Health System, accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset (N = 60,879) to construct predictive models of preeclampsia across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted preeclampsia with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.82, and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts. While our machine learning approach identified known risk factors of preeclampsia (such as blood pressure, weight, and maternal age), it also identified other potential risk factors, such as complete blood count related characteristics for the antepartum period. Our model not only has utility for earlier identification of patients at risk for preeclampsia, but given the prediction accuracy exceeds what is currently achieved in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.

Prevalence and determinants of oral and cervicogenital HPV infection: Baseline analysis of the Michigan HPV and Oropharyngeal Cancer (MHOC) cohort study.

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection in college-age participants reporting no lifetime sexual partners. Reporting a single recent partner was associated with a lower oral HPV prevalence (PR 0.39, 95% CI: 0.16, 0.96) than reporting no recent (but at least one ever) partner. No similar protective effect was seen for cervicogenital HPV. Both oral and cervicogenital prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and the age 23+ populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.

Social Media Addiction during COVID-19-Mandated Physical Distancing: Relatedness Needs as Motives.

In the early stages of the coronavirus disease 2019 (COVID-19) pandemic, national lockdowns and stay-at-home orders were implemented by many countries to curb the rate of infection. An extended stay-at-home period can frustrate people's need for relatedness, with many turning to social media to interact with others in the outside world. However, social media use may be maladaptive due to its associations with social media addiction and psychosocial problems. Our study was set at this special context to examine the associations among social media addiction, two aspects of relatedness needs (i.e., satisfaction and frustration), and two prominent psychosocial problems (i.e., depressive symptoms and loneliness). The participants were 1048 residents of the U.K. or U.S. (46% men, mean age = 44.10 years, SD = 12.59, age range: 18-65). The results indicated significant positive associations between relatedness need frustration and social media addiction as well as significant positive associations between social media addiction and the two types of psychosocial problems. More importantly, both of these significant associations were strong enough to partially explain the significant positive associations between relatedness need frustration and the two types of psychosocial problems. These findings provided some support for relatedness need frustration as a motivation of social media addiction.

Multiple Aerial Targets Re-Identification by 2D- and 3D- Kinematics-Based Matching.

This paper presents two techniques in the matching and re-identification of multiple aerial target detections from multiple electro-optical devices: 2-dimensional and 3-dimensional kinematics-based matching. The main advantage of these methods over traditional image-based methods is that no prior image-based training is required; instead, relatively simpler graph matching algorithms are used. The first 2-dimensional method relies solely on the kinematic and geometric projections of the detected targets onto the images captured by the various cameras. Matching and re-identification across frames were performed using a series of correlation-based methods. This method is suitable for all targets with distinct motion observed by the camera. The second 3-dimensional method relies on the change in the size of detected targets to estimate motion in the focal axis by constructing an instantaneous direction vector in 3D space that is independent of camera pose. Matching and re-identification were achieved by directly comparing these vectors across frames under a global coordinate system. Such a method is suitable for targets in near to medium range where changes in detection sizes may be observed. While no overlapping field of view requirements were explicitly imposed, it is necessary for the aerial target to be detected in both cameras before matching can be carried out. Preliminary flight tests were conducted using 2-3 drones at varying ranges, and the effectiveness of these techniques was tested and compared. Using these proposed techniques, an MOTA score of more than 80% was achieved.

Development and evaluation of safety and effectiveness of novel cancer screening tests for routine clinical use with applications to multicancer detection technologies.

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.

Incidence and clearance of oral and cervicogenital HPV infection: longitudinal analysis of the MHOC cohort study.

OBJECTIVES: The Michigan HPV and Oropharyngeal Cancer study aimed to evaluate patterns of oral and cervicogenital human papillomavirus (HPV) infection prevalence, incidence, and clearance as well as their relationship to sexual behaviours. DESIGN: Cohort SETTING: General public in and around Ann Arbor, Michigan. PARTICIPANTS: 394 college-age and older-adult participants of both sexes provided oral samples, and 325 completed at least 2 visits. 130 who provided a cervicogenital samples, and 127 completed at least 2 visits. OUTCOMES: Incidence and clearance rates as well as HRs for oral and cervicogenital HPV. RESULTS: Oral HPV infections were transient, with only 16% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 46 days (95% CI 37 to 58). In contrast, cervicogenital infections were more persistent, with 56% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 87 days (95% CI 74 to 102). HPV vaccination was associated with reduced incidence of cervicogenital HPV infection (HR 0.63; 95% CI 0.47 to 0.83) but not oral HPV infection. Incidence of oral HPV infection was associated with 2+ recent deep kissing partners (HR 2.00; 95% CI 1.13 to 3.56). Incidence of both oral (HR: 1.70; 95% CI 1.08 to 2.68) and cervicogenital (HR 2.46; 95% CI 1.69 to 3.59) was associated with 2+ recent sexual partners. CONCLUSIONS: Detection of oral HPV was highly transient, but incidence was associated with recent deep kissing and sexual partners. Detection of cervicogenital HPV was more persistent, and incidence was positively associated with recent sexual partners and negatively associated with HPV vaccination.

Nicotine dependence of cigarette and heated tobacco users in Japan, 2019: a cross-sectional analysis of the JASTIS Study.

OBJECTIVES: Japan is currently the biggest market of heated tobacco products (HTPs) in the world. Little is known about nicotine dependence among HTP users. Thus, the objective was to assess the association of type of tobacco use and time-to-first-use, a marker of nicotine dependence. METHODS: A cross-sectional analysis of the 2019 data from an internet cohort study was conducted. The analytical sample consisted of 2147 current (≥1 day use in the past 30 days) HTP and/or conventional cigarette users, aged 25+ years. Marginal structural binomial regression was used to estimate nicotine dependence prevalence ratios (PRs) for each category of tobacco use (exclusive daily cigarette, exclusive HTP (≥1 day), dual HTP+daily cigarette, dual HTP+non-daily cigarette), relative to exclusive, non-daily cigarette smoking. RESULTS: Using a 5 min cut-off for time-to-first-use, the prevalence of nicotine dependence was higher among dual users of HTP and daily cigarettes (PR=1.38; 95% CI: 1.05 to 1.82) and exclusive, daily cigarette users (PR=1.48; 95% CI: 1.15 to 1.91), relative to exclusive, non-daily cigarette users. However, nicotine dependence among exclusive HTP users, and dual HTP+non-daily cigarette users, did not differ from that of exclusive, non-daily cigarette users. When using 15 and 30 min cut-offs, all types of users, including exclusive HTP, had higher levels of nicotine dependence relative to exclusive, non-daily cigarette users. CONCLUSIONS: Regardless of HTP use, daily cigarette users had higher prevalence of nicotine dependence compared with non-daily cigarette users. Exclusive HTP users had similar (or potentially higher) dependence compared with exclusive, non-daily cigarette users. Longitudinal studies are needed to interrogate the public health implications of growing HTP use worldwide.

Perceptions and Challenges Experienced by African Physicians When Prescribing Methotrexate for Rheumatic Disease: An Exploratory Study.

OBJECTIVE: Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations. METHODS: African physicians who self-identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L-HDI versus MH-HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI. RESULTS: Physicians (23 rheumatologists; six internists) from 29 African countries were interviewed (15 L-HDI; 14 MH-HDI). Identified barriers to MTX use included inconsistent MTX supply (reported by 87% L-HDI versus 43% MH-HDI), compounded by financial restrictions (reported by 93% L-HDI versus 64% MH-HDI), patient hesitancy based partly on cultural beliefs and societal roles (reported by 71%), few prescribers (reported by 33%), prevalent infections (especially viral hepatitis, tuberculosis, and human immunodeficiency virus), and both availability and cost of monitoring tests. MTX pretreatment evaluation and starting and maximal doses were similar between L-HDI countries and MH-HDI countries. CONCLUSION: The challenges of treating rheumatic disease in African countries include unreliable drug availability and cost, limited subspecialists, and patient beliefs. Adapting recommendations for MTX use in the context of prevalent endemic infections; ensuring safe but feasible MTX monitoring strategies, enhanced access to stable drug supply, and specialized rheumatology care; and improving patient education are key to reducing the burden of rheumatic diseases in L-HDI countries.

The Mexico SimSmoke tobacco control policy model: Development of a simulation model of daily and nondaily cigarette smoking.

BACKGROUND: Nondaily smoking has been on the rise, especially in Mexico. While Mexico has strengthened its tobacco control policies, their effects on nondaily smokers have gone largely unexamined. We developed a simulation model to estimate the impact of tobacco control policies on daily and nondaily smoking in Mexico. METHODS: A previously validated Mexico SimSmoke model that estimated overall trends in smoking prevalence from 2002 through 2013 was extended to 2018 and adapted to distinguish daily and nondaily smoking prevalence. The model was then validated using data from Mexican surveys through 2016. To gauge the potential effects of policies, we compared the trends in smoking under current policies with trends from policies kept at their 2002 levels. RESULTS: Between 2002 and 2016, Mexico SimSmoke underestimated the reduction in male and female daily smoking rates. For nondaily smoking, SimSmoke predicted a decline among both males and females, while survey rates showed increasing rates in both genders, primarily among ages 15-44. Of the total reduction in smoking rates predicted by the model by 2018, tax policies account for more than 55%, followed by health warnings, cessation treatment, smoke-free air laws, and tobacco control spending. CONCLUSIONS: Although Mexico SimSmoke did not successfully explain trends in daily and nondaily smoking, it helps to identify gaps in surveillance and policy evaluation for nondaily smokers. Future research should consider appropriate measures of nondaily smoking prevalence, trajectories between daily and nondaily smoking, and the separate impact of tobacco control policies on each group.