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Information on COVID-19 vaccination effects on mortality among patients hospitalized with COVID-19 could inform vaccination outreach efforts and increase understanding of patient risk. Determine the associations of vaccination status with mortality in adult patients hospitalized with COVID-19. This retrospective cohort study assessed the characteristics and mortality rates of adult patients hospitalized with COVID-19 across 21 healthcare systems in the USA from January 1, 2021, to January 31, 2022. Adult patients admitted to participating hospitals who had COVID-19 diagnoses and/or positive PCR tests and completed their hospital stay via discharge or death. In-hospital mortality vs. discharge (outcome) and patient age, sex, race, ethnicity, BMI, insurance status, comorbidities, and vaccination status extracted from the electronic health record (EHR). Of 86,732 adult patients hospitalized with COVID-19, 45,082 (52%) were female, mean age was 60 years, 20,800 (24%) were Black, and 22,792 (26.3%) had one or more COVID-19 vaccinations. Statistically adjusted mortality rates for unvaccinated and vaccinated patients were 8.3% (95% CI, 8.1–8.5) and 5.1% (95% CI, 4.8–5.4) respectively (7.9% vs. 4.5% with no immune compromise). Vaccination was associated with especially large reductions in mortality for obese (OR = 0.67; 95% CI 0.56–0.80) and severely obese (OR = 0.52; 95% CI, 0.41–0.67) patients and for older patients (OR = 0.99; 95% CI, 0.98–0.99). Mortality likelihood was higher later in the study period (August 2021–January 31, 2022) than earlier (January 1, 2021–July 30, 2021) (OR = 1.10; 95% CI = 1.04–1.17) and increased significantly for vaccinated patients from 4.6% (95% CI, 3.9–5.2%) to 6.5% (95% CI, 6.2–6.9%). Patients vaccinated for COVID-19 had reduced mortality, especially for obese/severely obese and older individuals. Vaccination’s protective effect against mortality declined over time and hospitalized obese and older individuals may derive especially great benefit from prior vaccination against SARS-CoV-2.

PURPOSE: Continued smoking after the diagnosis of cancer can markedly worsen oncology treatment side effects, cancer outcomes, cancer mortality, and all-cause mortality. Conversely, mounting evidence demonstrates that smoking cessation by patients with cancer improves outcomes. A cancer diagnosis often serves as a teachable moment, characterized by high motivation to quit. However, too few patients with cancer who smoke are offered evidence-based smoking cessation treatment, and too few engage in such treatment. METHODS AND MATERIALS: The National Cancer Institute commissioned Tobacco Control Monograph 23, Treating Smoking in Cancer Patients: An Essential Component of Cancer Care, to review and synthesize the evidence that clarifies the need to intervene with smoking in cancer care. RESULTS: Although many patients with newly diagnosed cancer who smoke make quit attempts, many of these are unsuccessful, and among those who successfully quit, relapse is common. Indeed, an estimated 12.2% of adults ever diagnosed with cancer reported they currently smoked (National Health Interview Survey, 2020). Patients with cancer who smoke are likely to benefit from smoking cessation treatments, including counseling and US Food and Drug Administration–approved medications, and there are many effective strategies to increase delivery of smoking cessation treatment in cancer care settings. CONCLUSION: Smoking cessation is among the most effective treatment options for improving the likelihood of survival, quality of life, and overall health of patients with cancer who smoke. It is important for cancer care clinicians and patients to realize that it is never too late to quit smoking and that there are clear benefits to doing so, regardless of cancer type.

People coping with a mental illness and/or addictive disorders have a very high prevalence of smoking cigarettes. The Bucket Approach, a free online training, tailors evidence-based tobacco dependence interventions for behavioral health clinicians to increase the likelihood that they will also address the tobacco use of their patients. From October 2019 through August 2021, 999 people enrolled in and 447 people completed the training. Individuals who completed the training evaluated it highly with an overall mean score of 8.4 (scale = 1 for very poor to 10 for very good). 3- and 6-month follow-up surveys documented continued impact. The training resulted in substantial changes in beliefs about treating tobacco dependence. For example, before training, 18.3% of trainees strongly agreed with the statement, "The skills currently possessed by behavioral health clinicians can be easily applied to the treatment of tobacco dependence." This increased to 40.7% at the end of training.

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.

There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes “Core” items for minimal assessment of tobacco use at initial and follow-up time points, and an “Extension” set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. Clin Cancer Res; 22(8); 1907–13. ©2016 AACR.

This file contains the NCI-AACR tobacco use questionnaire and notes about its use.

This file contains detailed information about the methodology.

Smoking cessation results in improved cancer treatment outcomes. However, the factors associated with successful implementation of cessation programs in cancer care settings are not well understood. This paper presents the reach the reach and effectiveness of cessation programs implemented in NCI-Designated Cancer Centers in the Cancer Center Cessation Initiative (C3I). An observational, cross-sectional study was conducted among C3I Cancer Centers from July 1, 2019 and December 31, 2019 (N = 38). Reach was calculated as the proportion of patients reporting current smoking that received cessation treatment and was analyzed overall and by organizational characteristics. Smoking abstinence rates were determined by the proportion of participants self-reporting smoking abstinence in the previous 7 and 30 days at 6 months after treatment. On average, nearly 30% of patients who smoked received any cessation treatment. In-person counseling was most implemented but reached an average of only 13.2% of patients who smoked. Although less frequently implemented, average reach was highest for counseling provided via an interactive voice response system (55.8%) and telephone-based counseling (18.7%). Reach was higher at centers with more established programs, electronic health record referral systems, and higher smoking prevalence. At 6-month follow-up, about a fifth of participants on average had not smoked in the past 7 days (21.7%) or past 30 days (18.6%). Variations in reach by organizational characteristics suggest that leadership engagement and investment in technology-facilitated programs may yield higher levels of reach. Understanding which implementation and intervention strategies facilitate greater cessation treatment reach and effectiveness could lead to improved outcomes among cancer patients who smoke.

Purpose Hospitalization affords an opportunity to reduce smoking, but fewer than half of patients who smoke receive evidence-based cessation treatment during inpatient stays. This study evaluated a pharmacist-led, electronic health record (EHR)–facilitated opt-out smoking cessation intervention designed to address this need. Methods Analyses of EHR records for adult patients who smoked in the past 30 days admitted to an academic medical center in the upper Midwest were conducted using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. The reach of a pharmacist-led, EHR-facilitated protocol for smoking cessation treatment was assessed by comparing patients’ receipt of nicotine replacement therapy (NRT) and tobacco quitline referral before and after implementation. χ2 tests, t tests, and multiple logistic regression models were used to compare reach across patient demographic groups to assess treatment disparities and the representativeness of reach. Adoption of the program by hospital services was also assessed. Results Of the 70 hospital services invited to implement the program, 88.6% adopted it and 78.6% had eligible admissions. Treatment reach increased as rates of delivering NRT rose from 43.6% of eligible patients before implementation to 50.4% after implementation (P < 0.0001) and quitline referral rates rose from 0.9% to 11.9% (P < 0.0001). Representativeness of reach by sex and ethnicity improved after implementation, although disparities by race and age persisted after adjustment for demographics, insurance, and primary diagnosis. Pharmacists addressed tobacco use for eligible patients in 62.5% of cases after protocol implementation. Conclusion Smoking cessation treatment reach and representativeness of reach improved after implementation of a proactive, pharmacist-led, EHR-facilitated opt-out smoking cessation treatment protocol in adult inpatient services.

OBJECTIVES Current screening questions for pediatric tobacco smoke exposure are suboptimal. Factors influencing screening accuracy, particularly in the pediatric inpatient setting, are unknown. Our objective was to identify facilitators of and barriers to parental disclosure of smoke exposure when screened during their child’s hospitalization and strategies to promote accurate disclosure. METHODS This qualitative study was conducted with a convenience sample of parents of children admitted to the medical and surgical unit of a Midwest tertiary care children’s hospital. Eligible parents included those with documented disclosure of smoke exposure in the child’s electronic health record. A researcher trained in qualitative methods conducted semistructured, in-depth interviews with parents regarding their experiences with smoke exposure screening in the inpatient pediatric setting. Two researchers independently identified concepts directed at barriers, facilitators, and strategies for effective screening, which were compared and reconciled by a third researcher. RESULTS Facilitators of disclosing their child’s smoke exposure included the following: (1) the caregiver’s internal characteristic(s) promoting disclosure, (2) perceived relevance of the screening question to the child’s health, and (3) the questioner being viewed positively. Barriers included the following: (1) fear of negative consequences, (2) a vague question, (3) lack of knowledge, (4) guilt, and (5) unconducive environment and timing. The strategies parents suggested to improve screening for smoke exposure included the following: (1) communicate preemptively, (2) provide specific exposure examples, (3) improve questioner-caregiver rapport, and (4) improve screening environment and timing. CONCLUSIONS Parents identified various mechanisms to improve tobacco smoke exposure screening. The facilitators, barriers, and strategies provide opportunities to improve the inpatient pediatric screening process.

This Viewpoint discusses the ways in which the tobacco industry can advance their stated goals of harm reduction and a smoke-free future.

IntroductionMost tobacco treatment efforts target healthcare settings, because about 75% of smokers in the United States visit a primary care provider annually. Yet, 25% of patients may be missed by such targeting.AimsTo describe patients who smoke but infrequently visit primary care – their characteristics, rates of successful telephone contact, and acceptance of tobacco treatment.MethodsTobacco Cessation Outreach Specialists ‘cold-called’ those without a primary care visit in the past year, offering tobacco dependence treatment. Age, sex, insurance status, race, ethnicity, electronic health record (EHR) patient-portal status and outreach outcomes were reported.ResultsOf 3,407 patients identified as smokers in a health system registry, 565 (16.6%) had not seen any primary care provider in the past year. Among 271 of those called, 143 (53%) were successfully reached and 33 (23%) set a quit date. Those without visits tended to be younger, male, some-day versus every-day smokers (42 vs. 44 years, P = 0.004; 48% vs. 40% female, P = 0.0002, and 21% vs. 27% some-day, P = 0.003), and less active on the EHR patient portal (33% vs. 40%, P = 0.001).ConclusionsA substantial proportion of patients who smoke are missed by traditional tobacco treatment interventions that require a primary care visit, yet many are receptive to quit smoking treatment offers.

Background: Ensuring equitable access to smoking cessation services for cancer patients is necessary to avoid increasing disparities in tobacco use and cancer outcomes. In 2017, the Cancer Center Cessation Initiative (C3I) funded National Cancer Institute (NCI)-designated Cancer Centers to integrate evidence-based smoking cessation programs into cancer care. We describe the progress of C3I Cancer Centers in expanding the reach of cessation services across cancer populations. Methods: Cancer centers (n=17) reported on program characteristics and reach (the proportion of smokers receiving evidence-based cessation treatment) for two 6-month periods. Reach was calculated overall and by patient gender, race, ethnicity, and age. Results: Average reach increased from 18.5% to 25.6% over 1 year. Reach increased for all racial/ethnic groups, and in particular for American Indian/Alaska Native (6.6-24.7%), Asian/Native Hawaiian/Pacific Islander (7.3-19.4%), and black (18.8-25.9%) smokers. Smaller gains in reach were observed among Hispanic smokers (19.0-22.8%), but these were similar to gains among non-Hispanic smokers (18.9-23.9%). By age group, smokers aged 18-24 years (6.6-14.5%) and >65 years (16.1-24.5%) saw the greatest increases in reach. Conclusion: C3I Cancer Centers achieved gains in providing smoking cessation services to cancer patients who smoke, thereby reducing disparities that had existed across important subgroups. Taking a population-based approach to integrating tobacco treatment into cancer care has potential to increase reach equity. Implementation strategies including targeted and proactive outreach to patients and interventions to increase providers' adoption of evidence-based smoking cessation treatment may advance reach even further.

Background: Although people who smoke cigarettes are overrepresented among hospital inpatients, few are connected with smoking cessation treatment during their hospitalization. Training, accountability for medication use, and monitoring of all patients position pharmacists well to deliver cessation interventions to all hospitalized patients who smoke. Methods: A large Midwestern University hospital implemented a pharmacist-led smoking cessation intervention. A delegation protocol for hospital pharmacy inpatients who smoked cigarettes gave hospital pharmacists the authority to order nicotine replacement therapy (NRT) during hospitalization and upon discharge, and for referral to the Wisconsin Tobacco Quit Line (WTQL) at discharge. Eligible patients received the smoking cessation intervention unless they actively refused (ie, “opt-out”). The program was pilot tested in phases, with pharmacist feedback between phases, and then implemented hospital-wide. Interviews, surveys, and informal mechanisms identified ways to improve implementation and workflows. Results: Feedback from pharmacists led to changes that improved workflow, training and patient education materials, and enhanced adoption and reach. Refining implementation strategies across pilot phases increased the percentage of eligible smokers offered pharmacist-delivered cessation support from 37% to 76%, prescribed NRT from 2% to 44%, and referred to the WTQL from 3% to 32%. Conclusion: Hospitalizations provide an ideal opportunity for patients to make a tobacco quit attempt, and pharmacists can capitalize on this opportunity by integrating smoking cessation treatment into existing inpatient medication reconciliation workflows. Pharmacist-led implementation strategies developed in this study may be applicable in other inpatient settings.

The assessment of tobacco withdrawal is important for both research and clinical purposes. This study describes the psychometric development of a revised version of the 28-item Wisconsin Smoking Withdrawal Scale (WSWS; Welsch et al., Experimental and Clinical Psychopharmacology, 1999, 7, p. 354). Because the different contexts of use sometimes permit only brief assessment, this revision has produced both a brief and longer form using an updated pool of candidate items. For the revised Wisconsin Smoking Withdrawal Scale 2 (WSWS2), a candidate pool of 37 items was developed to measure nine putative withdrawal constructs. The stem and wording of items were revised as was the response scale. Data for psychometric analyses were derived from three smoking cessation randomized clinical trials conducted at the University of Wisconsin Center for Tobacco Research and Intervention. Dimensionality, internal consistency, and item characteristic analyses of the candidate items were conducted in a derivation sample to ascertain the factor structure and to identify items that could be used in the WSWS2 scales. Confirmatory factor analyses (CFAs) of reduced item sets and factor structure were conducted in two validation samples along with reliability and validity analyses. Derivation and validation sample analyses yielded a longer version of the WSWS2 (WSWS2-L) with 19 items and six subscales (Craving, Negative Affect, Hunger, Sleep, Restlessness, and Concentration) and a brief 6-item version (WSWS2-B). In validation sample analyses, both the WSWS2-L and the WSWS2-B demonstrated good reliability and validity as well as good fit in CFAs. The WSWS2-L and WSWS2-B possess improved construct coverage, fewer items, and other enhancements relative to the WSWS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

BackgroundTobacco smoke exposure leads to numerous adverse health effects in children. Providing cessation interventions to caregivers who smoke during pediatric hospitalizations can help protect children from such exposure. Both pediatric registered nurses (RNs) and pediatric respiratory therapists (RTs) are well positioned to provide these interventions. Little is known about their rates of participation in cessation efforts. Our objective was to compare the attitudes and practice of pediatric RNs versus pediatric RTs to evaluate their relative cessation-intervention practices in the in-patient pediatric setting.MethodsAn online survey was sent to pediatric RNs and RTs at 4 tertiary pediatric hospitals in California. The survey assessed individual demographics, work environment, experience, beliefs, and practices related to smoking cessation activities. Questions used 3-point and 5-point Likert scales and were compared with the chi-square test. Institutions with a response rate < 20% were excluded.ResultsA total of 401 respondents were included in the final analysis (292 RNs, 109 RTs). RTs versus RNs were older (42.0 y vs 35.4 y, respectively, P < .001) and more likely to be former smokers (29.9% vs 13.3%, respectively, P < .001). RNs reported lower levels of confidence in discussing smoking cessation with parents, with 11.7% saying they felt "very confident" compared to 29.0% of RTs (P < .001). RNs also reported screening for smoke exposure less frequently than RTs, with 18.8% responding "often" or "always" compared to 28.9% of RTs (P = .033). RNs had lower rates of advising parents "to make a smoke-free home policy" compared to RTs (ie, 13.4% vs 26.9%, respectively, P = .002).ConclusionsCompared to in-patient pediatric RNs, RTs reported higher rates of confidence in providing cessation interventions, screening for smoke exposure, and counseling on reducing smoke exposure, suggesting that they may be better positioned for intervening. These results can inform the design of an in-patient cessation intervention for caregivers of hospitalized children.

When in the tree xylem, maple sap is void of microbial contaminants, including bacteria, yeast, and molds. Once tapped, however, the liquid which is comprised primarily of water, becomes a nutrient...

Introduction Greater use of nicotine replacement therapy (NRT) is related to smoking cessation success, but the causal direction is unclear. This study characterized the relationship between NRT use and smoking lapse and relapse. Methods Participants (N = 416 smokers; 57% female, 85% White) were recruited from primary care for a smoking cessation factorial experiment and analyzed if abstaining ≥1 day in the first 2 weeks post-target quit day (TQD). Participants were randomized to counseling and 8 versus 26 weeks of nicotine patch plus nicotine gum post-TQD. Participants carried electronic dispensers that timestamped each gum use. Participants who lapsed (smoked after abstaining) within 6 weeks post-TQD were matched with nonlapsers (n = 146 pairs) on multiple variables. We compared lapsers’ versus matched nonlapsers’ gum use in the 5 days before and after the lapsers’ first lapse. Results By week 6 post-TQD, 63% of participants lapsed. Compared with nonlapsers, lapsers used less gum 1 and 2 days pre-“lapse” and on the 5 days post-lapse. Lapsers used less gum during the 5 days post-lapse than the 5 days pre-lapse. Univariate survival analyses with lapsers showed greater gum use during both pre- and post-lapse periods predicted longer latency to relapse in the first 6 weeks. Conclusions In a smoking cessation attempt using nicotine patch plus gum, lapsers versus matched nonlapsers used less gum immediately preceding and following their first lapse. Lower mean gum use before and after lapses predicted a more rapid escalation to relapse. Decreased nicotine gum use both precedes and follows returns to smoking during cessation attempts. Implications This research examined electronically monitored nicotine gum use collected in real time and found that among smokers engaged in a quit attempt, lapsers (vs. matched nonlapsers) tended to decrease their gum use 1–2 days prior to lapsing and to further decrease their gum use from pre- to post-lapse. Decreased gum use pre-lapse may signal heightened lapse risk in 1–2 days, with lower level of gum use predicting a more precipitous course of relapse. These results encourage further exploration of objective measures of smoking medication use patterns to examine their signaling properties and to inform understanding of cessation failure. Clinical Trial Registration ClinicalTrials.gov NCT01120704.

Innovative medical products offer significant and potentially transformative impacts on health, but they create concerns about rising spending and whether this rise is translating into higher value...

Introduction Most people who smoke cigarettes are not willing (ie, not ready) to make a quit attempt (QA) at any given time. Unfortunately, interventions intended to increase QAs and the success of QAs are only modestly effective. Identifying processes leading to QAs and quitting success could guide intervention development. Aims and Methods This is a secondary analysis of a randomized factorial trial of 6 weeks of motivation-phase interventions among primary care patients (N = 517) who were initially unwilling to quit but were willing to reduce their smoking. Using logistic regression, we controlled for treatment condition and tested whether baseline or change in smoking-related constructs after 6 weeks of treatment predicted (1) making an at least 24 h QA between weeks 6 and 26 and (2) quitting success at week 26 (7-day point-prevalence abstinence among those who made a QA). Predictors included cigarettes/day, time to first cigarette, motivation to quit, quitting self-efficacy, anticipated urges to smoke if quit, positive affect, negative affect, and time spent around others who smoke. Results In multivariable models that included all smoking-related constructs, changes in the following variables predicted initiating a QA above and beyond other variables: greater baseline time to first cigarette (odds ratio [OR] = 1.60), increases in time to first cigarette (OR = 1.27), and increases in quitting self-efficacy (OR = 1.14). Increased motivation to quit predicted conversion of a QA into quitting success at 26 weeks (OR = 1.36). Conclusion Predictors of making a QA differed from predictors of quitting success. Predictors of QAs and success could each serve as important treatment targets of motivation-phase interventions. Implications Motivation-phase interventions for people initially unwilling to quit smoking cigarettes may be improved by striving to increase their (1) time to first cigarette and quitting self-efficacy to promote QAs and (2) motivation to quit to promote quit success. Future experimental tests of such interventions are needed to identify causal determinants of QAs and quitting success.

Background: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. Methods: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. Results: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46–1.70] and 1.04 (95% CI, 0.96–1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53–0.90). Conclusions: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. Impact: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3

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.

Alzheimer's disease (AD) is a devastating neurological disorder for which soluble oligomers of the peptide amyloid-β (Aβ) are now recognized as the neurotoxic species. Metal-based therapeutics are uniquely suited to target Aβ, with ruthenium-based (Ru) complexes emerging as propitious candidates. Recently, azole-based Ru(III) complexes were observed to modulate the aggregation of Aβ in solution, where the inclusion of a primary amine proximal to the ligand coordination site improved the activity of the complexes. To advance these structure-activity relationships, a series of oxazole-based Ru complexes were prepared and evaluated for their ability to modulate Aβ aggregation. From these studies, a lead candidate