Time-varying associations of patient and tumor characteristics with cancer survival: an analysis of SEER data across 14 cancer sites, 2004-2017.

PURPOSE: Surveillance, Epidemiology, and End Results (SEER) cancer registries provides information about survival duration and cause of death for cancer patients. Baseline demographic and tumor characteristics such as age, sex, race, year of diagnosis, and tumor stage can inform the expected survival time of patients, but their associations with survival may not be constant over the post-diagnosis period. METHODS: Using SEER data, we examined if there were time-varying associations of patient and tumor characteristics on survival, and we assessed how these relationships differed across 14 cancer sites. Standard Cox proportional hazards models were extended to allow for time-varying associations and incorporated into a competing-risks framework, separately modeling cancer-specific and other-cause deaths. For each cancer site and for each of the five factors, we estimated the relative hazard ratio and absolute hazard over time in the presence of competing risks. RESULTS: Our comprehensive consideration of patient and tumor characteristics when estimating time-varying hazards showed that the associations of age, tumor stage at diagnosis, and race/ethnicity with risk of death (cancer-specific and other-cause) change over time for many cancers; characteristics of sex and year of diagnosis exhibit some time-varying patterns as well. Stage at diagnosis had the largest associations with survival. CONCLUSION: These findings suggest that proportional hazards assumptions are often violated when examining patient characteristics on cancer survival post-diagnosis. We discuss several interesting results where the relative hazards are time-varying and suggest possible interpretations. Based on the time-varying associations of several important covariates on survival after cancer diagnosis using a pan-cancer approach, the likelihood of the proportional hazards assumption being met or corresponding interpretation should be considered in survival analyses, as flawed inference may have implications for cancer care and policy.

Birth cohort relative to an influenza A virus's antigenic cluster introduction drives patterns of children's antibody titers.

An individual's antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of humoral immunity change as a function of age, calendar year, and birth cohort from cross-sectional data alone. We analyzed 1,589 longitudinal sera samples from 260 children across three studies in Nicaragua, 2006-16. Hemagglutination inhibition (HAI) titers were determined against four H3N2 strains, one H1N1 strain, and two H1N1pdm strains. We assessed temporal patterns of HAI titers using an age-period-cohort modeling framework. We found that titers against a given virus depended on calendar year of serum collection and birth cohort but not on age. Titer cohort patterns were better described by participants' ages relative to year of likely introduction of the virus's antigenic cluster than by age relative to year of strain introduction or by year of birth. These cohort effects may be driven by a decreasing likelihood of early-life infection after cluster introduction and by more broadly reactive antibodies at a young age. H3N2 and H1N1 viruses had qualitatively distinct cohort patterns, with cohort patterns of titers to specific H3N2 strains reaching their peak in children born 3 years prior to that virus's antigenic cluster introduction and with titers to H1N1 and H1N1pdm strains peaking for children born 1-2 years prior to cluster introduction but not being dramatically lower for older children. Ultimately, specific patterns of strain circulation and antigenic cluster introduction may drive population-level antibody titer patterns in children.

Strategies to Optimize Cervical Cancer Screening Rates Among Transgender and Gender-Diverse People Assigned Female at Birth.

Self-sampling for primary HPV detection for cervical cancer screening is now FDA-approved. Many persons interested in cervical cancer screening are eager to opt out of the invasive speculum exam and opt into the self-sampling. There is no limitation on which persons can choose self-sampling. Transgender, nonbinary, and gender-diverse assigned female at birth (TGD AFAB) people experience barriers such as gender dysphoria and discomfort with sensitive exams. They may find more comfort with this equivalent method of screening. However, no clinical guidelines describe the best practices to increase screening among this underserved population. Much community work needs to occur to make the language of screening gender-affirming for all participants. Solutions to currently invasive follow-up exams after abnormal screens need to be communicated in language directed by the TGD AFAB community.

A Model-Based 13C-Sucrose Breath Test Diagnostic for Gut Function Disorders Characterized by a Loss of Sucrase-Isomaltase Enzymatic Activity.

BACKGROUND: Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over interpreting the breath curves has limited their use. The activity of sucrose-isomaltase, the glucosidase enzyme responsible for sucrose hydrolysis, may be reduced in EED. We previously developed a mechanistic model describing the dynamics of the 13C-sucrose breath test (13C-SBT) as a function of underlying metabolic processes. OBJECTIVES: This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase. METHODS: We applied the mechanistic model to 2 sets of exploratory 13C-SBT experiments in healthy adult participants. First, 19 participants received differently labeled sucrose tracers (U-13C fructose, U-13C glucose, and U-13C sucrose) in a crossover study. Second, 16 participants received a sucrose tracer accompanied by 0, 100, and 750 mg of Reducose, a sucrase-isomaltase inhibitor. We evaluated a model-based diagnostic distinguishing between inhibitor concentrations using receiver operator curves, comparing with conventional statistics. RESULTS: Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66-0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91-0.99). CONCLUSIONS: Current summary approaches to interpreting 13C breath test curves may be limited to identifying only gross gut dysfunction. A mechanistic model-based approach improved interpretation of breath test curves characterizing sucrose metabolism.

Latent Class Analysis of Sexual Partnerships and Substance Use Across Generations.

Sexually transmitted infections (STIs) remain an important public health concern for people of all age groups, with older age groups experiencing a notable increase in STI burden. Historically, most research into STI risk behaviors has focused on adolescents and young adults, leaving a paucity of research on the ways STI risk factors change over the life course. Additionally, age and cohort trends in STI risk factors can be challenging to investigate with standard statistical tools as they can be collinear and are subject to sociocultural and generational influences. To help address these issues, we used multi-group latent class analysis to identify and compare risk behavior profiles defined by responses to three sexual activity and three substance use variables, across and within four age groups. We identified six behavior profiles in the unstratified dataset and five behavior profiles in each of the four age stratified groups. The five behavior profiles identified in each of the age categories appear to reflect a similar set of five underlying profile "archetypes," with the exact composition of each age category's five profiles varying in the magnitude that specific behaviors are endorsed. Interestingly, despite the similarity of profiles across the four age groups, analyses indicate that the experience of belonging to any one of these five archetypes differs by age group. This variance is likely due group specific age, period, and cohort effects, and may indicate that, when estimating one's STI risk, it is better to compare them to their peers than to the population as a whole.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of adults in the PATH Study in 2017-2019 vs 2019-2021.

INTRODUCTION: The use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the lung injuries outbreak, flavour bans, Tobacco 21 and the COVID-19 pandemic. METHODS: Using the Population Assessment of Tobacco and Health Study, we applied a multistate transition model to 28 061 adults in waves 4-5 (2017-2019) and 24 584 adults in waves 5-6 (2019-2021), estimating transition rates for initiation, cessation and switching products for each period overall and by age group. RESULTS: Cigarette initiation among adults who never used either product decreased from 2017-2019 to 2019-2021, but ENDS initiation did not significantly change. The persistence of ENDS-only use remained high (75%-80% after 1 year). Cigarette-only use transitions remained similar (88% remaining, 7% to non-current use and 5% to dual or ENDS-only use). In contrast, dual use to ENDS-only transitions increased from 9.5% (95% CI 7.3% to 11.7%) to 20.0% (95% CI 17.4% to 22.6%) per year, decreasing the persistence of dual use. The dual to cigarette-only use transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18-24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use. CONCLUSIONS: The persistence of ENDS use among adults remained high in 2019-2021, but a larger fraction of dual users transitioned to ENDS-only use compared with 2017-2019. Because the fraction of cigarette-only users switching to dual use remained low, especially among older adults, the public health implications of this change are minimal.

Leveraging infectious disease models to interpret randomized controlled trials: Controlling enteric pathogen transmission through water, sanitation, and hygiene interventions.

Randomized controlled trials (RCTs) evaluate hypotheses in specific contexts and are often considered the gold standard of evidence for infectious disease interventions, but their results cannot immediately generalize to other contexts (e.g., different populations, interventions, or disease burdens). Mechanistic models are one approach to generalizing findings between contexts, but infectious disease transmission models (IDTMs) are not immediately suited for analyzing RCTs, since they often rely on time-series surveillance data. We developed an IDTM framework to explain relative risk outcomes of an infectious disease RCT and applied it to a water, sanitation, and hygiene (WASH) RCT. This model can generalize the RCT results to other contexts and conditions. We developed this compartmental IDTM framework to account for key WASH RCT factors: i) transmission across multiple environmental pathways, ii) multiple interventions applied individually and in combination, iii) adherence to interventions or preexisting conditions, and iv) the impact of individuals not enrolled in the study. We employed a hybrid sampling and estimation framework to obtain posterior estimates of mechanistic parameter sets consistent with empirical outcomes. We illustrated our model using WASH Benefits Bangladesh RCT data (n = 17,187). Our model reproduced reported diarrheal prevalence in this RCT. The baseline estimate of the basic reproduction number [Formula: see text] for the control arm (1.10, 95% CrI: 1.07, 1.16) corresponded to an endemic prevalence of 9.5% (95% CrI: 7.4, 13.7%) in the absence of interventions or preexisting WASH conditions. No single pathway was likely able to sustain transmission: pathway-specific [Formula: see text] for water, fomites, and all other pathways were 0.42 (95% CrI: 0.03, 0.97), 0.20 (95% CrI: 0.02, 0.59), and 0.48 (95% CrI: 0.02, 0.94), respectively. An IDTM approach to evaluating RCTs can complement RCT analysis by providing a rigorous framework for generating data-driven hypotheses that explain trial findings, particularly unexpected null results, opening up existing data to deeper epidemiological understanding.

Associations of Demographics, Dependence, and Biomarkers With Transitions in Tobacco Product Use in a Cohort of Cigarette Users and Dual Users of Cigarettes and E-cigarettes.

INTRODUCTION: It is uncertain whether e-cigarettes facilitate smoking cessation in the real world. We aimed to understand whether and how transitions among cigarette, e-cigarette, and dual use are associated with sociodemographics, dependence measures, and biomarkers. AIMS AND METHODS: We followed 380 adult daily cigarette users and dual users every 2 months for up to 2 years. We estimated transition rates between noncurrent, cigarette-only, e-cigarette-only, and dual use states using a multistate transition model. We estimated univariable hazard ratios (HR) for demographics, dependence measures for cigarettes and e-cigarettes, biomarkers, spousal or partner behaviors, and other measures. RESULTS: We estimated that participants transitioned from cigarette-only to e-cigarette-only through a period of dual use. Dual users ceased smoking (transitioning to e-cigarette-only use) at a greater rate than cigarette-only users did (HR 2.44, 95% CI: 1.49, 4.02). However, of the 60% of dual users estimated to transition to single product use in 1 year, 83% would transition to cigarette-only use and only 17% to e-cigarette-only use. E-cigarette dependence measures were generally associated with reduced e-cigarette cessation rather than enhanced cigarette cessation. E-cigarette users motivated by harm or toxicity reduction or because of restrictions on where or when they could smoke had reduced rates of smoking relapse. Cigarette dependence and spousal smoking were barriers to cigarette cessation for dual users, while using e-cigarettes first in the morning, motivation to quit smoking, and sensory, social, and emotional enjoyment of e-cigarettes (secondary dependence motives) were facilitators of smoking cessation among dual users. CONCLUSIONS: Tobacco control policy and interventions may be informed by the barriers and facilitators of product transitions. IMPLICATIONS: Although e-cigarettes have the potential to promote smoking cessation, their real-world impact is uncertain. In this cohort, dual users were more likely to quit smoking than cigarette-only users, but the overall impact was small because most dual users returned to cigarette-only use. Moreover, e-cigarette dependence promoted continued dual use rather than smoking cessation. Yet, high motivation to quit smoking and the sensory, social, and emotional enjoyment of e-cigarettes facilitated smoking cessation in dual users. Better understanding the barriers and facilitators of transitions can help to develop regulations and interventions that lead to more effective use of e-cigarettes for smoking cessation.

Patterns of poly tobacco use among adults in the Population Assessment of Tobacco and Health (PATH) study, 2013-2017: a multistate Markov transition analysis.

BACKGROUND: A better understanding of sociodemographic transition patterns between single, dual and poly tobacco product use may help improve tobacco control policy interventions. METHODS: HRs of transition between never, non-current (no past 30-day use), cigarette, e-cigarette, other combustible, smokeless tobacco (SLT), dual and poly tobacco use states in adults were estimated for age, sex, race/ethnicity, education and income using a multistate model for waves 1-4 of the Population Assessment of Tobacco and Health study (2013-2017), a US-based cohort study, accounting for complex survey design. RESULTS: Sole cigarette and SLT use were persistent, with 77% and 78% of adults continuing use after one wave. Other use states were more transient, with 29%-48% of adults reporting the same pattern after one wave. If single-product users transitioned, it was most likely to non-current use while dual or poly cigarette users were most likely to transition to exclusive cigarette use. Males were more likely than females to initiate combustible product use after a history of no use, and after a period of tobacco use cessation. Hispanic and non-Hispanic black participants initiated cigarette use at higher rates than non-Hispanic white participants, and had higher rates of experimentation with tobacco products between study waves. Lower socioeconomic status was associated with higher rates of transition into combustible tobacco use. CONCLUSIONS: Dual and poly tobacco use is largely transient, while single-use patterns are more stable over time. Transitions differ by age, sex, race/ethnicity, education and income, which may influence the impact of current and future tobacco control efforts.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of youth and adults in the PATH Study in 2015-2017 vs 2017-2019.

INTRODUCTION: It is unknown how recent changes in the tobacco product marketplace have impacted transitions in cigarette and electronic nicotine delivery system (ENDS) use. METHODS: A multistate transition model was applied to 24 242 adults and 12 067 youth in waves 2-4 (2015-2017) and 28 061 adults and 12 538 youth in waves 4 and 5 (2017-2019) of the Population Assessment of Tobacco and Health Study. Transition rates for initiation, cessation and product transitions were estimated in multivariable models, accounting for gender, age group, race/ethnicity and daily versus non-daily product use. RESULTS: Changes in ENDS initiation/relapse rates depended on age, including among adults. Among youth who had never established tobacco use, the 1-year probability of ENDS initiation increased after 2017 from 1.6% (95% CI 1.4% to 1.8%) to 3.8% (95% CI 3.4% to 4.2%). Persistence of ENDS-only use (ie, 1-year probability of continuing to use ENDS only) increased for youth from 40.7% (95% CI 34.4% to 46.9%) to 65.7% (95% CI 60.5% to 71.1%) and for adults from 57.8% (95% CI 54.4% to 61.3%) to 78.2% (95% CI 76.0% to 80.4%). Persistence of dual use similarly increased for youth from 48.3% (95% CI 37.4% to 59.2%) to 60.9% (95% CI 43.0% to 78.8%) and for adults from 40.1% (95% CI 37.0% to 43.2%) to 63.8% (95% CI 59.6% to 67.6%). Youth and young adults who used both products became more likely to transition to ENDS-only use, but middle-aged and older adults did not. CONCLUSIONS: ENDS-only and dual use became more persistent. Middle-aged and older adults who used both products became less likely to transition to cigarette-only use but not more likely to discontinue cigarettes. Youth and young adults became more likely to transition to ENDS-only use.