Size and position matter.

The 2013 Nobel Prize in Physiology or Medicine emphasizes the progress made in understanding the molecular mechanisms that underpin the vesicular movement of cargo through the exocytic and endocytic pathways. Attention now focuses on those mechanisms that govern the relative size and position of the many different membrane-bound compartments. These homeostatic mechanisms are discussed in this issue of Nature Reviews Molecular Cell Biology and must be integrated so as to satisfy the needs of the cell and the organism.

Implementation, enrollment, and engagement in an opt-out telehealth pharmacist-assisted tobacco treatment program for patients seen in oncology outpatient clinics.

OBJECTIVE: To describe the workflow, reach, cost, and self-reported quit rates for an opt-out tobacco treatment program (TTP) for patients seen in 43 oncology outpatient clinics. METHODS: Between May 25, 2021, and December 31, 2022, adult patients (≥18 years) visiting clinics affiliated with the Medical University of South Carolina Hollings Cancer Center were screened for smoking status. Those currently smoking were referred to a telehealth pharmacy-assisted TTP. An attempt was made to contact referred patients by phone. Patients reached were offered free smoking cessation counseling and a 2-week starter kit of nicotine replacement medication. A random sample of 420 patients enrolled in the TTP were selected to participate in a telephone survey to assess smoking status 4 to 12 months after enrollment. RESULTS: During the reference period 35,756 patients were screened and 9.3% were identified as currently smoking. Among the 3319 patients referred to the TTP at least once, 2393 (72.1%) were reached by phone, of whom 426 (12.8%) were ineligible for treatment, 458 (13.8%) opted out of treatment, and 1509 (45.5%) received treatment. More than 90% of TTP enrollees smoked daily, with an average of 13.1 cigarettes per day. Follow-up surveys were completed on 167 of 420 patients, of whom 23.4% to 33.5% reported not smoking; if all nonresponders to the survey are counted as smoking, the range of quit rates is 9.3% to 13.3%. CONCLUSION: The findings demonstrate the feasibility of reaching and delivering smoking cessation treatments to patients from a diverse set of geographically dispersed oncology clinics.

Smoking prevalence and association with sociodemographic variables in cancer clinical trial participants.

BACKGROUND: Tobacco use (smoking) causes adverse clinical outcomes among patients with cancer, including increased cancer-related mortality. In participants in cancer clinical trials, the prevalence of tobacco use and the factors associated with tobacco use are not well described. METHODS: Data were examined from participants enrolled in SWOG cancer clinical treatment trials between 2016 and 2022 who reported their smoking status at trial enrollment. Baseline variables (smoking status, insurance type, zip code, and demographic factors) were obtained from patient registration forms. Bivariate and multivariable associations were examined via logistic regression. RESULTS: Among 4326 patients enrolled in 29 trials, 48.1% reported currently/previously smoking, including 12.4% currently, 4.9% recently, and 30.7% formerly. Ever smoking was more commonly reported in males, patients aged ≥65 years, patients with Medicaid or no insurance, patients from areas of high socioeconomic deprivation, and rural patients. Patients of Hispanic ethnicity and Asian and Pacific Islander patients were less likely to have ever smoked. In multivariable regression, patients with lung cancer were most likely to report ever smoking compared to patients with breast cancer (odds ratio, 4.98; p < .001). CONCLUSIONS: In the first comprehensive evaluation of smoking status among trial participants enrolled in National Cancer Institute network group treatment trials, nearly half reported ever smoking and one in six reported current or recent smoking. Smoking was more common among vulnerable population patients defined by demographic and socioeconomic factors. Tobacco use should be routinely assessed and reported in clinical trials to help reduce the negative cancer and overall health effects of persistent tobacco use and to address disparities among patients with cancer.

Cost-effectiveness of point of care smoking cessation interventions in oncology clinics.

BACKGROUND: We examined the cost-effectiveness of providing systematic smoking cessation interventions to oncology patients at point-of-care. METHODS: A decision analytic model was completed from the healthcare payer's perspective and included all incident cancer cases involving patients who smoke in New Brunswick, Canada (n = 1040), cancer site stratifications, and risks of mortality, continued smoking, and cancer treatment failure over one year. Usual care (no cessation support) was compared to the standard Ottawa Model for Smoking Cessation (OMSC) intervention, and to OMSC plus unlimited cost-free stop smoking medication (OMSC + SSM), including nicotine replacement therapy, varenicline, or bupropion. Primary outcomes were incremental cost per quit (ICQ) and incremental cost per cancer treatment failure avoided (ICTFA). RESULTS: The ICQ was $C143 and ICTFA $C1193 for standard OMSC. The ICQ was $C503 and ICTFA was $C5952 for OMSC + SSM. The number needed to treat (NNT) to produce one quit was 9 for standard OMSC and 4 for OMSC + SSM, and the NNT to avoid one first-line treatment failure was 78 for OMSC and 45 for OMSC + SSM. Both were cost-effective in 100% of 1000 simulations. CONCLUSIONS: Given the high clinical benefits and low incremental costs, systematic smoking cessation interventions should be a standard component of first-line cancer treatment.

Development of an Intervention Targeted to Patients with Cancers Not Typically Perceived as Smoking-Related.

Smoking by cancer patients impairs treatment outcomes and prognoses across cancer types. Previous research shows greater smoking cessation motivation and quit rates among patients with cancers strongly linked to smoking (i.e., thoracic, head and neck) compared to other cancer types (e.g., melanoma). Therefore, there is a need to increase cessation motivation among patients with malignancies less commonly associated with smoking. Yet, no targeted educational materials exist to meet this information gap. This manuscript describes the development of theory-based self-help educational materials, targeted by cancer type, to increase motivation to quit smoking among patients with cancers not widely perceived as smoking-related (i.e., breast, melanoma, bladder, colorectal, gynecological). Using a three-phase iterative process, we first conducted in-depth interviews with our intended audience (N = 18) to identify information needs and nuanced content. Themes included patients' low knowledge about the connection between smoking and cancer etiology and outcomes; negative affect, habit, dependence, and weight gain as quitting barriers; and a preference for positive and non-judgmental content. Second, content creation was based on interview findings, the scientific literature, and framed following the teachable moment model. Last, learner verification and revisions via interviews with 22 patients assessed suitability of draft materials, with generally favorable responses. Resulting edits included tailoring cost savings to the cancer context, explaining cessation medications, and increasing appeal by improving the diversity (e.g., race) of the individuals in the photographs. The final booklets are low cost, easy to disseminate, and-pending efficacy studies-may expand smoking cessation to a wider spectrum of cancer patients.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. AIMS AND METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. CONCLUSIONS: The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Negative affect and the utilization of tobacco treatment among adult smokers with cancer.

OBJECTIVE: We investigated the patterns of tobacco treatment utilization among US adult smokers with cancer and the role of negative affect as potential individual-level psychosocial barriers and facilitators influencing quit attempts and tobacco treatment utilization. METHODS: We analyzed data from the adult sample in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study. Using structural equation modeling, we examined (1) the association between cancer diagnosis and negative affect (e.g., depressive mood, anxiety, and distress) and (2) the associations between negative affect and smoking cessation behaviors (i.e., quit attempts and tobacco treatment utilization). RESULTS: Compared to adults without cancer, cancer survivors were more likely to have attempted to quit tobacco use in the past 12 months (p < 0.05) and experienced increased negative affect (p < 0.01). However, negative affect appeared to be a psychological barrier to quit attempts, as it was associated with lower likelihood of attempting to quit (p < 0.05). On the other hand, among past-12-month quit attempters, negative affect was related to higher likelihood of using any type of tobacco treatment (p < 0.001). CONCLUSIONS: Negative affect may be a potential underlying mechanism in the relationship between cancer diagnosis status and quit attempts and tobacco treatment utilization, influencing the utilization of tobacco treatment among smokers with cancer. Research is needed to investigate whether integrating emotional management in the oncology setting may effectively aid smoking cessation among patients with cancer.

Cost evaluation of tobacco control interventions in clinical settings: A systematic review.

Elucidating the cost implications of tobacco control interventions is a prerequisite to their adoption in clinical settings. This review fills a knowledge gap in characterizing the extent to which cost is measured in tobacco control studies. A search of English literature was conducted in the following electronic databases: MEDLINE, EconLit, PsychINFO, and CINAHL using MeSH terms from 2009 to 2018. Studies were reviewed by two independent reviewers and included if they were conducted in U.S. inpatient or outpatient facilities and reported costs associated with a tobacco control intervention. They were categorized according to evaluation type, clinical setting, target population, cost measures, and stakeholder perspective. Bias risk was evaluated for RCTs. Seventeen publications were included, representing counseling interventions (n = 8) and combination (i.e., counseling and pharmacotherapy) interventions (n = 9). Studies were categorized by evaluation type: cost-effectiveness analysis (n = 10), cost utility analysis (n = 3) and cost identification (n = 4). The selected studies targeted the following populations: general adults (n = 6), hospitalized/inpatient (n = 4), military/veterans (n = 4), individuals with low socioeconomic status (n = 4), mental health or medical comorbidities (n = 2), and pregnant women (n = 2). Intervention costs included personnel, medication, education material, technology, and overhead costs. Stakeholder perspectives included: healthcare organization (n = 10), payer (n = 8), patient (n = 2), and societal (n = 1). Few studies have reported the cost of tobacco control interventions in clinical settings. Cost is a critical outcome that should be consistently measured in evaluations of tobacco control interventions to promote their uptake in clinical settings.

Modeling rectal cancer to advance neoadjuvant precision therapy.

Progress in rectal cancer therapy has been hindered by the lack of effective disease-specific preclinical models that account for the unique molecular profile and biology of rectal cancer. Thus, we developed complementary patient-derived xenograft (PDX) and subsequent in vitro tumor organoid (PDTO) platforms established from preneoadjuvant therapy rectal cancer specimens to advance personalized care for rectal cancer patients. Multiple endoscopic samples were obtained from 26 Stages 2 and 3 rectal cancer patients prior to receiving 5FU/RT and implanted subcutaneously into NSG mice to generate 15 subcutaneous PDXs. Second passaged xenografts demonstrated 100% correlation with the corresponding human cancer histology with maintained mutational profiles. Individual rectal cancer PDXs reproduced the 5FU/RT response observed in the corresponding human cancers. Similarly, rectal cancer PDTOs reproduced significant heterogeneity in cellular morphology and architecture. PDTO in vitro 5FU/RT treatment response replicated the clinical 5FU/RT neoadjuvant therapy pathologic response observed in the corresponding patient tumors (p < 0.05). The addition of cetuximab to the 5FU/RT regiment was significantly more sensitive in the rectal cancer PDX and PDTOs with wild-type KRAS compared to mutated KRAS (p < 0.05). Considering the close relationship between the patient's cancer and the corresponding PDX/PDTO, rectal cancer patient-derived research platforms represent powerful translational research resources as population-based tools for biomarker discovery and experimental therapy testing. In addition, our findings suggest that cetuximab may enhance RT effectiveness by improved patient selection based on mutational profile in addition to KRAS or by developing a protocol using PDTOs to identify sensitive patients.

Considering Systemic Barriers to Treating Tobacco Use in Clinical Settings in the United States.

The Comorbidity Workgroup of the Tobacco Treatment Research Network, within the Society for Research on Nicotine and Tobacco, previously highlighted the need to provide tobacco treatment to patients diagnosed with comorbid physical and mental health conditions. Yet, systemic barriers in the United States health care system prevent many patients who present for medical treatment from getting the evidence-based tobacco treatment that they need. The identified barriers include insufficient training in the epidemiologic impact of tobacco use, related disorders, and pharmacological and behavioral treatment approaches; misunderstanding among clinicians about the effectiveness of tobacco treatment; lack of therapeutic support from clinical staff; insufficient use of health information technology to improve tobacco use identification and treatment; and limited time and reimbursement for clinicians to provide treatment. We highlight three vignettes demonstrating the complexities of practical barriers at the health care system level. We consider each of the barriers in turn and discuss evidence-based strategies that could be implemented in the clinical care of patients with comorbid conditions. In addition, in the absence of compelling data to guide implementation approaches, we offer suggestions for potential strategies and avenues for future research. Implications: Three vignettes highlighted in this article illustrate some systemic barriers to providing tobacco treatment for patients being treated for comorbid conditions. We explore the barriers to tobacco treatment and offer suggestions for changes in training, health care systems, clinical workflow, and payment systems that could enhance the reach and the quality of tobacco treatment within the US health care system.

SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation.

Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases and progeria. Here, we show that SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype to the recently identified regulator of nuclear envelope reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly. The function of SIRT2 therefore extends beyond the regulation of microtubules to include the regulation of nuclear envelope dynamics.

Effect of an Evidence-based Inpatient Tobacco Dependence Treatment Service on 1-Year Postdischarge Health Care Costs.

BACKGROUND: In 2014, the Medical University of South Carolina (MUSC) implemented a Tobacco Dependence Treatment Service (TDTS) consistent with the Joint Commission (JC) standards recommending that hospitals screen patients for smoking, provide cessation support, and follow-up contact for relapse prevention within 1 month of discharge. We previously demonstrated that patients exposed to the MUSC TDTS were approximately half as likely to be smoking one month after discharge and 23% less likely to have a 30-day hospital readmission. This paper examines whether exposure to the TDTS influenced downstream health care charges 12 months after patients were discharged from the hospital. METHODS: Data from MUSC's electronic health records, the TDTS, and statewide health care utilization datasets (eg, hospitalization, emergency department, and ambulatory surgery visits) were linked to assess how exposure to the MUSC TDTS impacted health care charges. Total health care charges were compared for patients with and without TDTS exposure. To reduce potential TDTS exposure selection bias, propensity score weighting was used to balance baseline characteristics between groups. The cost of delivering the MUSC TDTS intervention was calculated, along with cost per smoker. RESULTS: The overall adjusted mean health care charges for smokers exposed to the TDTS were $7299 lower than for those who did not receive TDTS services (P=0.047). The TDTS cost per smoker was modest by comparison at $34.21 per smoker eligible for the service. DISCUSSION: Results suggest that implementation of a TDTS consistent with JC standards for smoking cessation can be affordably implemented and yield substantial health care savings that would benefit patients, hospitals, and insurers.

Effect of an Evidence-based Inpatient Tobacco Dependence Treatment Service on 30-, 90-, and 180-Day Hospital Readmission Rates.

INTRODUCTION: Smoking is a risk factor for hospitalization and interferes with patient care due to its effects on pulmonary function, wound healing, and interference with treatments and medications. Although benefits of stopping smoking are well-established, few hospitals provide tobacco dependence treatment services (TDTS) due to cost, lack of mandatory tobacco cessation standards and lack of evidence demonstrating clinical and financial benefits to hospitals and insurers for providing services. METHODS: This study explored the effect of an inpatient TDTS on 30-, 90-, and 180-day hospital readmissions. To carry out this work, 3 secondary datasets were linked, which included clinical electronic health record data, tobacco cessation program data, and statewide health care utilization data. Odds ratios (ORs) were calculated using inverse propensity score-weighted logistic regression models, with program exposure as the primary independent variable and 30 (90 and 180)-day readmission rates as the dependent variable, and adjustment for putative covariates. RESULTS: Odds of readmission were compared for patients who did and did not receive TDTS. At 30 days postdischarge, smokers exposed to the TDTS had a lower odds of readmission (OR=0.77, P=0.031). At 90 and 180 days, odds of readmission remained lower in the TDTS group (ORs=0.87 and 0.86, respectively), but were not statistically significant. DISCUSSION: Findings from the current study, which are supported by prior studies, provide evidence that delivery of TDTS is a strategy that may help to reduce hospital readmissions.

Evaluation of a Dedicated Tobacco Cessation Support Service for Thoracic Cancer Center Patients.

CONTEXT: Cancer patients' continued tobacco use results in poorer therapeutic outcomes including decreased quality of life and survival. OBJECTIVE: To assess reach and impact of a free, opt-out, telephone-based tobacco cessation program for thoracic cancer center patients. DESIGN: Observational study. SETTING: Comprehensive Cancer Center in Western New York. PARTICIPANTS: Current or recent (within past 30 days) tobacco-using thoracic cancer center patients referred to a tobacco cessation support service between October 2010 and October 2012 at a Comprehensive Cancer Center (n = 942/1313 referrals were eligible for cessation support). INTERVENTION: A free, opt-out, telephone-based cessation service that was implemented as standard of care. Cessation specialists had patient-guided conversations that assessed readiness to quit; methods used in the past provided cessation strategies and worked to set up a quit date. There was an average of 35.9 days between referral and first contact. MAIN OUTCOME MEASURES: Program reach (referral and participation rates) and impact (as self-reported cessation outcomes measured twice after referral). RESULTS: Of 942 patients, 730 (77.5%) referred to and called by a tobacco cessation service participated in at least 1 cessation support call, of which 440 of 730 (60.3%) were called for follow-up and 89.5% (394/440) participated. In total, 20.2% (69/342) of current smokers at referral reported at least 7-day abstinence at follow-up. Among current smokers at referral and first contact, being married (odds ratio [OR] = 2.05; 95% confidence interval [CI], 1.01-4.18) and having a lower Eastern Cooperative Oncology Group (ECOG) performance score (OR = 4.05; 95% CI, 1.58-10.39) were associated with quitting at follow-up, after controlling for demographic, clinical, and health behavior characteristics. CONCLUSIONS: Our results demonstrate that 78% of thoracic cancer center patients, if contacted, participated at least once in this cessation support service; for current smokers at referral and first contact, being married and having a lower ECOG performance score were associated with self-reported quitting at follow-up. Other organizations may find our results useful while implementing a systematic way to identify tobacco-using patients as part of routine care and to improve available cessation support services.

Feasibility of Implementing a Hospital-Based "Opt-Out" Tobacco-Cessation Service.

OBJECTIVE: To assess the feasibility and outcomes of implementing a hospital-based "opt-out" tobacco-cessation service. METHODS: In 2014, the Medical University of South Carolina adopted a policy that all hospitalized patients who self-report using tobacco be referred to tobacco-cessation service. This is a descriptive study of a real-world effort to implement guidelines for a hospital-based cessation service consistent with Joint Commission's standards. Between February 2014 and May 2015, 42 061 adults were admitted to the Medical University of South Carolina Hospital. Eligible current cigarette smokers were referred to the tobacco-cessation service, which consisted of a bedside consult and phone follow-up 3, 14, and 30 days after hospital discharge using interactive-voice-response. The primary study outcomes evaluated the proportions of smokers reached by the bedside counselor and/or phone follow-up, smokers who opted out, and smokers who self-reported not smoking when last contacted by phone. RESULTS: Records identified 8423 smokers, of whom 69.4% (n = 5843) were referred into the service. One full-time bedside counselor was able to speak with 1918 (32.8%) patients, of whom 96 (5%) denied currently smoking and 287 (14.9%) refused counselling. Reach at follow-up was achieved for 703 (55%) smokers who received bedside counselling and 1613 (49%) who did not, yielding an overall follow-up reach rate of 60%. Of those reached by phone, 36.4% reported not smoking (51% vs. 27% for those who did and did not receive bedside counselling, respectively). Intent-to-treat abstinence rate was 13.5% according to the last known smoking status. CONCLUSIONS: Findings from this study suggest that an inpatient smoking-cessation service with an "opt-out" approach can positively impact short-term cessation outcomes. IMPLICATIONS: (1) The findings demonstrate the feasibility of implementing an automated large-scale opt-out tobacco-cessation service for hospitalized patients that is consistent with the Joint Commission recommended standards for treating tobacco dependence. (2) Receiving a bedside tobacco-cessation consult while hospitalized increased the use of stop smoking medications and abstinence from smoking after discharge from the hospital. (3) Even in those patients who did not receive a bedside consult, 5% accepted a referral to the South Carolina Tobacco Quitline to get help to stop smoking.

The Association between Smoking Abstinence and Mortality in the National Lung Screening Trial.

RATIONALE: Smoking is the largest contributor to lung cancer risk, and those who continue to smoke after diagnosis have a worse survival. Screening for lung cancer with low-dose computed tomography (LDCT) reduces mortality in high-risk individuals. Smoking cessation is an essential component of a high-quality screening program. OBJECTIVES: To quantify the effects of smoking history and abstinence on mortality in high-risk individuals who participated in the NLST (National Lung Screening Trial). METHODS: This is a secondary analysis of a randomized controlled trial (NLST). MEASUREMENTS AND MAIN RESULTS: Measurements included self-reported demographics, medical and smoking history, and lung cancer-specific and all-cause mortality. Cox regression was used to study the association of mortality with smoking status and pack-years. Kaplan-Meier survival curves were examined for differences in survival based on trial arm and smoking status. Current smokers had an increased lung cancer-specific (hazard ratio [HR], 2.14-2.29) and all-cause mortality (HR, 1.79-1.85) compared with former smokers irrespective of screening arm. Former smokers in the control arm abstinent for 7 years had a 20% mortality reduction comparable with the benefit reported with LDCT screening in the NLST. The maximum benefit was seen with the combination of smoking abstinence at 15 years and LDCT screening, which resulted in a 38% reduction in lung cancer-specific mortality (HR, 0.62; 95% confidence interval, 0.51-0.76). CONCLUSIONS: Seven years of smoking abstinence reduced lung cancer-specific mortality at a magnitude comparable with LDCT screening. This reduction was greater when abstinence was combined with screening, highlighting the importance of smoking cessation efforts in screening programs.

Significance of pregnancy test false negative results due to elevated levels of ß-core fragment hCG.

Very high levels of ß-core fragment human chorionic gonadotrophin (ßcf-hCG) are reported to potentially cause false negative results in point-of-care (POC)/over-the-counter (OTC) pregnancy tests. To investigate this further, women's daily early morning urine samples, collected prior to conception and during pregnancy, were analysed for intact, free ß-, and ßcf-hCG. The proportion of ßcf-hCG was found to be related to that of hCG produced and in circulation. Therefore, best practice for accuracy testing of POC/OTC pregnancy tests would be to test devices against clinical samples containing high levels of ßcf-hCG as well as standards spiked with biologically relevant ratios.

Sec16 determines the size and functioning of the Golgi in the protist parasite, Trypanosoma brucei.

The Sec16 homologue in Trypanosoma brucei has been identified and characterized. TbSec16 colocalizes with COPII components at the single endoplasmic reticulum exit site (ERES), which is next to the single Golgi stack in the insect (procyclic) form of this organism. Depletion of TbSec16 reduces the size of the ERES and the Golgi, and slows growth and transport of a secretory marker to the cell surface; conversely, overexpression of TbSec16 increases the size of the ERES and Golgi but has no effect on growth or secretion. Together these data suggest that TbSec16 regulates the size of the ERES and Golgi and this size is set for optimal growth of the organism.