Impact of Joint Lung Cancer Screening and Cessation Interventions Under the New Recommendations of the U.S. Preventive Services Task Force

IntroductionIn 2021, the U.S. Preventive Services Task Force (USPSTF) revised its lung cancer screening recommendations expanding its eligibility. As more smokers become eligible, cessation interventions at the point of screening could enhance the benefits. Here, we evaluate the effects of joint screening and cessation interventions under the new recommendations.MethodsA validated lung cancer natural history model was used to estimate lifetime number of low-dose computed tomography screens, percentage ever screened, lung cancer deaths, lung cancer deaths averted, and life-years gained for the 1960 U.S. birth cohort aged 45 to 90 years (4.5 million individuals). Screening occurred according to the USPSTF 2013 and 2021 recommendations with varying uptake (0%, 30%, 100%), with or without a cessation intervention at the point of screening with varying effectiveness (15%, 100%).ResultsScreening 30% of the eligible population according to the 2021 criteria with no cessation intervention (USPSTF 2021, 30% uptake, without cessation intervention) was estimated to result in 6845 lung cancer deaths averted and 103,725 life-years gained. These represent 28% and 34% increases, respectively, relative to screening according to the 2013 guidelines (USPSTF 2013, 30% uptake, without cessation intervention). Adding a cessation intervention at the time of the first screen with 15% effectiveness (USPSTF 2021, 30% uptake, with cessation intervention with 15% effectiveness) was estimated to result in 2422 additional lung cancer deaths averted (9267 total, ∼73% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 322,785 life-years gained (∼318% increase). Screening 100% of the eligible according to the 2021 guidelines with no cessation intervention (USPSTF 2021, 100% uptake, without cessation intervention) was estimated to result in 23,444 lung cancer deaths averted (∼337% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 354,330 life-years gained (∼359% increase). Adding a cessation intervention with 15% effectiveness (USPSTF 2021, 100% uptake, with cessation intervention with 15% effectiveness) would result in 31,998 lung cancer deaths averted (∼497% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 1,086,840 life-years gained (∼1309% increase).ConclusionsJoint screening and cessation interventions would result in considerable lung cancer deaths averted and life-years gained. Adding a one-time cessation intervention of modest effectiveness (15%) results in comparable life-years gained as increasing screening uptake from 30% to 100% because while cessation decreases mortality from many causes, screening only reduces lung cancer mortality. This simulation indicates that incorporating cessation programs into screening practice should be a priority as it can maximize overall benefits.     

Systematic Review of Health Economic Evaluations Focused on Artificial Intelligence in Healthcare: The Tortoise and the Cheetah

ObjectivesThis study aimed to systematically review recent health economic evaluations (HEEs) of artificial intelligence (AI) applications in healthcare. The aim was to discuss pertinent methods, reporting quality and challenges for future implementation of AI in healthcare, and additionally advise future HEEs.MethodsA systematic literature review was conducted in 2 databases (PubMed and Scopus) for articles published in the last 5 years. Two reviewers performed independent screening, full-text inclusion, data extraction, and appraisal. The Consolidated Health Economic Evaluation Reporting Standards and Philips checklist were used for the quality assessment of included studies.ResultsA total of 884 unique studies were identified; 20 were included for full-text review, covering a wide range of medical specialties and care pathway phases. The most commonly evaluated type of AI was automated medical image analysis models (n = 9, 45%). The prevailing health economic analysis was cost minimization (n = 8, 40%) with the costs saved per case as preferred outcome measure. A total of 9 studies (45%) reported model-based HEEs, 4 of which applied a time horizon >1 year. The evidence supporting the chosen analytical methods, assessment of uncertainty, and model structures was underreported. The reporting quality of the articles was moderate as on average studies reported on 66% of Consolidated Health Economic Evaluation Reporting Standards items.ConclusionsHEEs of AI in healthcare are limited and often focus on costs rather than health impact. Surprisingly, model-based long-term evaluations are just as uncommon as model-based short-term evaluations. Consequently, insight into the actual benefits offered by AI is lagging behind current technological developments.     

Cardiac-type total anomalous pulmonary venous return is not benign

ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making.     

Frame Invariance and Scalability of Neural Operators for Partial Differential Equations

Partial differential equations (PDEs) play a dominant role in the mathematical modeling of many complex dynamical processes. Solving these PDEs often requires prohibitively high computational costs, especially when multiple evaluations must be made for different parameters or conditions. After training, neural operators can provide PDEs solutions significantly faster than traditional PDE solvers. In this work, invariance properties and computational complexity of two neural operators are examined for transport PDE of a scalar quantity. Neural operator based on graph kernel network (GKN) operates on graph-structured data to incorporate nonlocal dependencies. Here we propose a modified formulation of GKN to achieve frame invariance. Vector cloud neural network (VCNN) is an alternate neural operator with embedded frame invariance which operates on point cloud data. GKN-based neural operator demonstrates slightly better predictive performance compared to VCNN. However, GKN requires an excessively high computational cost that increases quadratically with the increasing number of discretized objects as compared to a linear increase for VCNN.     

Molecular modeling in cardiovascular pharmacology: Current state of the art and perspectives

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Making colonoscopy-based screening more efficient: A “gateopener” approach

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a “gateopener” for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single (“gateopener”) FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such “gateopener screening” (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a “gateopener” low-threshold FIT would substantially enhance efficiency of colonoscopy screening.     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

Temporal Expectation Hastens Decision Onset But Does Not Affect Evidence Quality

The ability to predict the timing of forthcoming events, known as temporal expectation, has a strong impact on human information processing. Although there is growing consensus that temporal expectations enhance the speed and accuracy of perceptual decisions, it remains unclear whether they affect the decision process itself, or non-decisional (sensory/motor) processes. Here, healthy human participants (N = 21; 18 female) used predictive auditory cues to anticipate the timing of low-contrast visual stimuli they were required to detect. Modeling of the behavioral data using a prominent sequential sampling model indicated that temporal expectations speeded up non-decisional processes but had no effect on decision formation. Electrophysiological recordings confirmed and extended this result: temporal expectations hastened the onset of a neural signature of decision formation but had no effect on its build-up rate. Anticipatory α band power was modulated by temporal expectation and co-varied with intrinsic trial-by-trial variability in behavioral and neural signatures of the onset latency of the decision process. These findings highlight how temporal predictions optimize our interaction with unfolding sensory events.SIGNIFICANCE STATEMENT Temporal expectation enhances performance, but the locus of this effect remains debated. Here, we contrasted the two dominant accounts: enhancement through (1) expedited decision onset, or (2) an increase in the quality of sensory evidence. We manipulated expectations about the onset of a dim visual target using a temporal cueing paradigm, and probed the locus of the expectation effect with two complementary approaches: drift diffusion modeling (DDM) of behavior, and estimation of the onset and progression of the decision process from a supramodal accumulation-to-bound signal in simultaneously measured EEG signals. Behavioral modeling and neural data provided strong, converging evidence for an account in which temporal expectations enhance perception by speeding up decision onset, without affecting evidence quality.     

A subjective analysis of participants’ views in a study of experimental modelling of imposed airway obstruction in infants and children

Deliberate airway obstruction is a well-recognised form of child abuse and one of the most common causes of death in cases of child homicide. Although classical signs such as petechial haemorrhages can be helpful in raising the suspicion of mechanical asphyxia, they are not always present. Therefore, distinguishing between bruising caused by accidents, medical conditions or non-accidental injury remains challenging. We aimed to characterise bruising patterns which are potentially more consistent with deliberate airway obstruction by means of an experimental modelling study. The first results of our project were previously published and demonstrated that bruising anywhere on the head may be consistent with deliberate upper airway obstruction. In this paper, we present the findings of a questionnaire carried out during the modelling to assess participants’ perception of force and consider how variables such as age, use of adjuncts and force distribution may affect bruising patterns in deliberate airway obstruction. Statistical analysis of our results showed that participants felt they were using less force in scenarios involving the infant rather than the child resuscitation dummy as well as when using adjuncts, meaning marks are likely to be more subtle. Therefore, in such cases it is important to examine for other signs of asphyxiation (such as petechiae) and consider the possibility that adjuncts might have been used which could make picking up localised injuries more difficult. Our results also showed that participants often felt force was not distributed evenly across the digits, reporting the greatest force through either the thumb in isolation or the thumb plus another digit in up to nearly 50% of cases. This suggests that just one or two bruises may be consistent with deliberate airway obstruction.