The Effect of Age and Other Patient Characteristics on Outcomes Among Nontransplanted Patients Who Were Treated With First-Line Lenalidomide, Bortezomib, and Dexamethasone: Results From the ConnectⓇ MM Registry.

BACKGROUND: Lenalidomide (R), bortezomib (V), and dexamethasone (d) is a standard-of-care regimen in newly diagnosed multiple myeloma (NDMM); however, characteristics and outcomes for nontransplanted patients receiving frontline RVd are not well understood. PATIENTS: The ConnectⓇ MM Registry is a large, US, multicenter, prospective observational cohort study of NDMM patients. METHODS: This analysis investigated characteristics and outcomes of patients who received RVd alone or followed by Rd or R (RVd ± Rd/R) who did not undergo frontline autologous stem cell transplantation. RESULTS: As of August 2021, 314 of 1979 nontransplanted patients received RVd ± Rd/R as initial therapy. Of these, 135 were aged ≤ 65 years and 179 were > 65 years. 108 patients had time to relapse (TTR) of ≤ 12 months and 182 had TTR > 12 months. Baseline characteristics were comparable regardless of TTR and age group except renal function, which was more commonly impaired in older patients. Among patients aged ≤ 65 and > 65 years, median duration of first-line treatment was 6.3 and 9.0 months, median time to next line for those who received second-line therapy was 15.5 and 15.2 months, median progression-free survival (PFS) was 19.3 and 23.0 months, and median overall survival was 60.0 and 59.1 months, respectively. High-risk disease (per IMWG criteria) and high serum calcium were associated with higher hazard of progression or death; the adjusted PFS hazard ratio with respect to age (≤ 65 vs. > 65 years) based on multivariable analysis was 1.18 (0.89-1.57; P = .25). CONCLUSION: These results indicate RVd is active across age groups and provide a better understanding of outcomes with RVd in NDMM.

Differential responses to cigarette package labeling alternatives among adults who smoke: Results from a randomized trial.

INTRODUCTION: Little experimental research has evaluated whether the effects of cigarette package inserts with efficacy messages and/or pictorial health warning labels (PHWLs) differ across key subgroups of adults who smoke. METHODS: Adults who reported currently smoking (n=367) were randomly assigned to one of four groups: small text-only health warning labels (HWLs) on pack sides (control); inserts with efficacy messages and small HWLs (inserts-only); PHWLs showing harms of smoking (PHWLs-only); both (inserts+PHWLs). Participants received a 14-day supply of cigarettes labeled to reflect their group. Every evening over two weeks, participants reported forgoing and stubbing out cigarettes before they finished smoking over the prior 24 hours, combined into a binary indicator of either behavior (e.g., forgoing/stubbing). Separate mixed-effects logistic models were estimated to evaluate moderation of labeling group contrasts (i.e., PHWLs vs not; inserts vs. not; inserts-only vs. inserts+PHWLs; PHWLs-only vs. inserts+PHWLs) by baseline covariates (self-efficacy to quit, intention to quit, education, health literacy, time discounting), predicting day-level forgoing/stubbing. RESULTS: Education moderated PHWL effects, with PHWLs predicting more forgoing/stubbing only among those with low education (OR=4.68, p<0.001). Time discounting moderated insert effects, with inserts promoting fogoing/stubbing only among those with low time discounting (i.e., lower impulsivity; OR=4.35, p<0.001). CONCLUSIONS: Inserts with efficacy messages appear effective mostly among people with low time discounting, whereas PHWLs appear most effective amongst those with low education, suggesting their potential to address education-related disparities. Labeling strategies appeared equally effective across subgroups defined by self-efficacy to quit, quit intention, and health literacy. Combining inserts with PHWLs did not appear to mitigate moderation effects. IMPLICATIONS: This randomized trial with adults who smoke suggests that cigarette packs with inserts describing cessation benefits and tips can promote cessation-related behaviors (i.e., forgoing or stubbing out cigarettes) among those with low time discounting (i.e., low impulsivity). Alternative interventions may be needed for people with high time discounting, as found in cessation trials. Pictorial health warning labels (PHWLs) appear most effective among those with low education, potentially addressing education-related disparities. No differential effects were found for those with different levels of self-efficacy to quit, quit intentions, or health literacy. Combining inserts and PHWLs may not be more effective than either alone.

Self-reported attention and responses to cigarette package labels at the end of a two-week randomized trial of cigarette package labeling configurations.

INTRODUCTION: Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including potentially enhancing the effects of pictorial health warning labels (PHWLs). METHODS: A randomized trial with a 2×2 factorial design was conducted with adult smokers (n=356) assigned to either small text-only health warning labels (HWLs; control); inserts with cessation messages, and the small text-only HWLs (inserts-only); large PHWLs (PHWLs-only); both inserts and PHWLs (inserts + PHWLs). Participants received a 14-day supply of their preferred cigarettes with packs labeled to reflect their group. Upon finishing the trial, participants reported their past 14-day frequency of noticing, reading, thinking about smoking harms and cessation benefits, talking about labels, and forgoing cigarettes because of the labels. Ordered logistic models regressed these outcomes on labeling groups, and mediation analyses assessed whether attention (i.e. noticing, reading) to labels mediated effects of labeling exposure on other outcomes (i.e. thinking about harms/benefits, talking, forgoing). RESULTS: The inserts + PHWLs group reported higher frequencies than the control group for all outcomes. Compared to the control group, both the inserts-only and PHWLs-only groups reported higher frequency of noticing (AOR=3.53 and 2.46, respectively) and reading labels (AOR=2.89 and 1.71), thinking about smoking risks because of the labels (AOR=1.93 and 1.82), and talking about labels (AOR=2.30 and 2.70). Participants in the inserts-only group also reported more frequent thinking about quitting benefits (AOR=1.98). Attention mediated all labeling effects except for the contrast between PHWLs only and control. CONCLUSIONS: Compared to text-only HWLS, cigarette labeling that involves inserts, PHWLs, or both appears more effective at drawing attention to warnings, which mediated the effects on cessation-related psychosocial and behavioral outcomes.

Does e-cigarette use predict short-term smoking cessation behaviors among adults who smoke in Mexico? A longitudinal study.

INTRODUCTION: This study assessed quit attempts among adults who use cigarettes either exclusively or with e-cigarettes in Mexico, where non-daily smoking predominates. METHODS: An open cohort of Mexican adults who smoke was surveyed every four months from November 2018 to March 2021. Participants followed to the next survey were analyzed (n = 2220 individuals, 4560 observations). Multinomial logistic models regressed smoking quit attempts reported at the followup survey (ref = no attempt; tried to quit; sustained attempt of ≥30 days) on e-cigarette use frequency (none = ref; 1-2 days/week; ≥3 days/week), adjusting for sociodemographics and smoking-related variables. Additional models subdivided e-cigarette users by intentions to quit smoking in the next six months (i.e., yes/no), use of nicotine (i.e., yes/no), and vaping device used (i.e., open/closed). RESULTS: At 4-month follow-up, 32.7 % had tried to quit, and 2.9 % had quit for 30 days or more. Compared to those who smoke exclusively, occasional, and frequent e-cigarette users were more likely to try to quit (Adjusted Relative Risk Ratio or ARRR = 1.26 and 1.66, respectively) but no more likely to sustain their quit attempt. Among those who intended to quit smoking, e-cigarette users were no more likely to either try or sustain quit attempts. Furthermore, use of e-cigarettes with nicotine (59.6 %) was unassociated with cessation except that those who frequently used e-cigarettes with nicotine were more likely to try to quit than those who smoke exclusively (ARRR = 1.88). Device type used was not differentially associated with outcomes. CONCLUSIONS: Mexicans who smoke and use e-cigarettes appear more likely than those who smoke exclusively to try to quit but not to sustain abstinence.

Heated tobacco product use frequency, smoking quit attempts, and smoking reduction among Mexican adult smokers.

INTRODUCTION: Heated tobacco products (HTPs) are promoted as less harmful than cigarettes; nonetheless, whether HTPs help smokers quit is uncertain. METHODS: Data from 4067 Mexican adult smokers surveyed longitudinally every four months (November 2019-March 2021) were analyzed. Mixed-effects multinomial models regressed HTP use frequency (no use=reference; monthly; weekly; and daily use) on sociodemographics and tobacco/nicotine-related variables. Among participants who completed at least two surveys (n=2900) over four months, the duration of their longest smoking quit attempt (SQA) between surveys (SQAs: <30 days; ≥30 days; no SQA=reference) was regressed on HTP use frequency, and changes in the number of cigarettes smoked per day were regressed on HTP initiation between surveys, adjusting for covariates. RESULTS: Consistent predictors of all HTP use frequencies (monthly, weekly, or daily vs no use) were daily smoking >5 cigarettes (ARRR=1.69 [95% CI: 1.12-2.55], 1.88 [95% CI: 1.26-2.81] and 6.46 [95% CI: 3.33-12.52], respectively); e-cigarette use (ARRR =5.68 [95% CI: 3.38-9.53], 6.54 [95% CI: 4.06-10.55] and 2.59 [95% CI: 1.26-5.30]); lower HTP risk perceptions (ARRR=2.12 [95% CI: 1.50-30.00], 2.25 [95% CI: 1.63-3.10] and 2.00 [95% CI: 1.25-3.22]); exposure to HTP information inside (ARRR=2.13 [95% CI: 1.44-3.15], 2.13 [95% CI: 1.49-3.05] and 3.72 [95% CI: 2.28-6.09]) and outside stores (ARRR=2.36 [95% CI: 1.56-3.57], 2.32 [95% CI: 1.65-3.25] and 2.44 [95% CI: 1.41-4.24]) where tobacco is sold; having family (ARRR=2.46 [95% CI: 1.54-3.91], 2.90 [95% CI: 1.93-4.37] and 2.96 [95% CI: 1.52-5.77]) and friends (ARRR=5.78 [95% CI: 3.60-9.30], 4.98 [95% CI: 3.22-7.72] and 6.61 [95% CI: 2.91-15.01]) who use HTPs. HTP use frequency was not associated with quit attempts, except for monthly HTP use predicting SQAs lasting ≥30 days (ARRR=2.12 [95% CI: 1.17-3.85]). Initiation of HTP use was not associated with changes in smoking frequency. Limiting analysis to those who intend to quit smoking also yielded null results. CONCLUSIONS: Among Mexican adult smokers, frequency of HTP use was mostly not associated with either cessation behaviors or changes in cigarette consumption, suggesting that HTPs have limited to no effectiveness for smoking cessation.

Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study.

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.

Comparison of the Acute Postoperative Complications Between Isolated Talonavicular Versus Talonavicular and Subtalar (Double) Arthrodesis in Flatfoot Deformity.

BACKGROUND: Both isolated talonavicular arthrodesis and talonavicular and subtalar (such as double) arthrodesis can be effective treatments for adult-acquired flatfoot deformity (AAFD) with good success rates, but double arthrodesis has become more commonly performed in recent years. The purpose of this study is to evaluate whether isolated talonavicular versus talonavicular and subtalar arthrodesis led to significantly different 30-day postoperative complication rates in patients with AAFD. METHODS: We performed a retrospective review to identify a large cohort of adult patients with the diagnosis of AAFD or posterior tibial tendon deformity (PTTD) who underwent isolated talonavicular or talonavicular and subtalar arthrodesis between 2006 and 2020 from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). To investigate whether there was a difference in complication rate between the 2 surgical cohorts, we estimated logistic regression models and log-binomial models on each of the outcomes while also adjusting for sex and age. RESULTS: We found that there was no significant difference in the rate of major complications (P = .567) or readmissions (P = .567) between patients who underwent isolated talonavicular versus talonavicular and subtalar arthrodesis for AAFD. However, there was a significantly higher rate of minor complications in patients who underwent isolated talonavicular arthrodesis when compared with patients who underwent talonavicular and subtalar arthrodesis (P = .009). CONCLUSION: This study found that there was no increased risk of 30-day postoperative complications or readmissions with talonavicular and subtalar arthrodesis when compared with isolated talonavicular arthrodesis for AAFD. In addition, there was no increased risk of major complications for talonavicular and subtalar arthrodesis when compared with isolated talonavicular arthrodesis, and isolated talonavicular arthrodesis actually carried a higher risk of minor complications for this surgical cohort. This may provide valuable information for surgeons considering surgical treatment for a particular case of AAFD. LEVEL OF EVIDENCE: Level III.

Combining Inserts With Warning Labels on Cigarette Packs to Promote Smoking Cessation: A 2-Week Randomized Trial.

BACKGROUND: Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation. PURPOSE: To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes. METHODS: We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4-5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups. RESULTS: Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes. CONCLUSIONS: This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts.

Cigarette pack inserts (small leaflets inside packs) with messages about quitting benefits and tips to quit may promote smoking cessation. We randomly assigned 367 adult smokers to one of four groups: control group with small health warning labels (HWLs) on the side of packs; inserts with cessation messages and small HWLs; large picture HWLs showing health effects from smoking; inserts and large picture HWLs. Participants received a 14-day supply of their preferred cigarettes in packs that reflected their assigned group. Over 2 weeks, we surveyed participants 4­5 times a day during times when they smoked, asking their feelings about smoking and smoking-related harms, confidence to reduce cigarettes and quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported on the prior 24 hr: how often they thought about smoking harms and cessation benefits; conversations about smoking cessation or harms; and foregoing or stubbing out cigarettes before they finished smoking. People whose packs had inserts (with or without picture HWLs) were more likely than those whose packs did not include inserts (control group or picture HWLs only) to report foregoing or stubbing out of cigarettes. This study provides some evidence that inserts with cessation messages may promote smoking cessation.

Effect of body mass index on acute postoperative complications following Total Ankle Arthroplasty (TAA).

BACKGROUND: Total ankle arthroplasty (TAA) is an effective treatment for various ankle pathologies, but some concern remains for the high associated complication and failure rates relative to major joint arthroplasty of the hip and knee. Patient body mass index (BMI) is a modifiable and potentially important preoperative variable when evaluating postoperative complications. The purpose of this study is to evaluate the effect of BMI, age and sex on the acute postoperative complication rate after TAA. METHODS: We retrospectively reviewed adult patients who underwent TAA between 2006 and 2021 from the NSQIP database. Using overweight patients as the reference BMI group, we utilized log-binomial models to estimate risk ratios on outcomes while adjusting for sex and age to investigate whether there were significant adjusted differences in complication rates among the BMI groups. RESULTS: We found that, relative to overweight patients, there were no statistically significant differences in the risk of acute complications for underweight (BMI < 18.5) (P = .118), healthy weight (18.5≤BMI < 25) (P = .544), obese (30≤BMI < 40) (P = .930), or morbidly obese (BMI < 40) (P = .602) patients who underwent TAA. There were also no statistically significant differences in the risk of acute complications based on age category (P = .482,.824) or sex (P = .440) for TAA. Additionally, there were no significant differences between the BMI groups for either major complications (P = .980) or minor complications (P = .168). CONCLUSION: Ultimately, we found that BMI, age, and sex did not lead to statistically significant differences in the risk of complications within 30 days postoperatively for TAA, even when stratified by major vs minor complications. LEVEL OF EVIDENCE: Level III.

Real-World Utilization of Radiation Therapy in Multiple Myeloma: An Analysis of the Connect MM Registry.

PURPOSE: Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited. METHODS AND MATERIALS: The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis. RESULTS: A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 [enrolled 2009-2011] vs 2 [enrolled 2012-2016]). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028). CONCLUSIONS: Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.

Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial.

BACKGROUND: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease. METHODS: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors. RESULTS: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05). CONCLUSIONS: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

Association between Fluoxetine Use and Overall Survival among Patients with Cancer Treated with PD-1/L1 Immunotherapy.

Checkpoint inhibitors can be a highly effective antitumor therapy but only to a subset of patients, presumably due to immunotherapy resistance. Fluoxetine was recently revealed to inhibit the NLRP3 inflammasome, and NLRP3 inhibition could serve as a target for immunotherapy resistance. Therefore, we evaluated the overall survival (OS) in patients with cancer receiving checkpoint inhibitors combined with fluoxetine. A cohort study was conducted among patients diagnosed with lung, throat (pharynx or larynx), skin, or kidney/urinary cancer treated with checkpoint inhibitor therapy. Utilizing the Veterans Affairs Informatics and Computing Infrastructure, patients were retrospectively evaluated during the period from October 2015 to June 2021. The primary outcome was overall survival (OS). Patients were followed until death or the end of the study period. There were 2316 patients evaluated, including 34 patients who were exposed to checkpoint inhibitors and fluoxetine. Propensity score weighted Cox proportional hazards demonstrated a better OS in fluoxetine-exposed patients than unexposed (HR: 0.59, 95% CI 0.371-0.936). This cohort study among cancer patients treated with checkpoint inhibitor therapy showed a significant improvement in the OS when fluoxetine was used. Because of this study's potential for selection bias, randomized trials are needed to assess the efficacy of the association of fluoxetine or another anti-NLRP3 drug to checkpoint inhibitor therapy.

Highlighting the value of Alzheimer's disease-focused registries: lessons learned from cancer surveillance.

Like cancer, Alzheimer's disease and related dementias (ADRD) comprise a global health burden that can benefit tremendously from the power of disease registry data. With an aging population, the incidence, treatment, and mortality from ADRD is increasing and changing rapidly. In the same way that current cancer registries work toward prevention and control, so do ADRD registries. ADRD registries maintain a comprehensive and accurate registry of ADRD within their state, provide disease prevalence estimates to enable better planning for social and medical services, identify differences in disease prevalence among demographic groups, help those who care for individuals with ADRD, and foster research into risk factors for ADRD. ADRD registries offer a unique opportunity to conduct high-impact, scientifically rigorous research efficiently. As research on and development of ADRD treatments continue to be a priority, such registries can be powerful tools for conducting observational studies of the disease. This perspectives piece examines how established cancer registries can inform ADRD registries' impact on public health surveillance, research, and intervention, and inform and engage policymakers.

Treatment Patterns, Survival, Quality of Life, and Healthcare Resource Use Among Patients With Triple-Class Refractory Multiple Myeloma in US Clinical Practice: Findings From the Connect MM Disease Registry.

BACKGROUND: Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice. PATIENTS AND METHODS: Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included. Patient characteristics, treatment patterns, HRQoL, and HCRU were analyzed using descriptive statistics. OS was calculated using Kaplan-Meier methodology for the overall cohort and for patients with/without ≥1 post-TCR line of therapy (LOT). RESULTS: A total of 232 patients with TCR MM were included; 155 (67%) had ≥1 post-TCR LOT (post-TCR-Treated subgroup; median 9.9 months of follow-up). Most common post-TCR treatments were carfilzomib (47%), pomalidomide (40%), and daratumumab (26%); median treatment duration was 3.3 months. Median OS was 9.9 months in the overall population, 10.8 months in post-TCR-Treated patients, and 2.6 months for those with no new post-TCR LOT. HRQoL deteriorated and pain increased over 1 year of follow-up, with clinically meaningfully changes in EQ-5D (mean, -0.06 points) and FACT-G (mean, -9.9 points). 124 (53%) patients had ≥1 all-cause hospitalization and 58 (25%) had ≥1 MM-related hospitalization; median annualized length of stay was 35.3 and 42.9 days, respectively. CONCLUSION: The burden of TCR MM is substantial, emphasizing the need for more effective treatment options in the TCR setting.

Relationship of Nonsteroidal Anti-Inflammatory Drug Use During Pregnancy with Autism Spectrum Disorder and Intellectual Disability Among Offspring.

Objective: This study aimed to examine the association of nonsteroidal anti-inflammatory drug (NSAID) use by pregnant women during pregnancy with autism spectrum disorder (ASD) and intellectual disability (ID) in their children among Medicaid-insured mother-child dyads. Materials and Methods: We conducted a retrospective cohort study linking multiple datasets of South Carolina for the years between 2010 and 2017, in which the main exposure variable was NSAID use during pregnancy and outcome variables were ASD only, ID only, and ASD with ID. We conducted a multinomial logistic regression analysis, controlling for identified risk factors for ASD (mother's age, race, body-mass index, preeclampsia, and gestational diabetes). Results: NSAID use during pregnancy was found to be associated with ID only in both unadjusted and adjusted analyses. Children with mothers who had NSAID prescriptions were 26% more likely to have ID in comparison with children whose mothers did not have NSAID prescriptions (odds ratio: 1.26 [1.10-1.46]). The other risk factors identified for ASD were maternal age, race, preeclampsia, smoking, low birth weight, and obesity. For ID, the risk factors were maternal age, race, smoking, birth weight, overweight, and obesity, all of which were also associated with ASD with ID, except for overweight. Conclusions: NSAID usage during pregnancy was found to be associated with ID only and not with ASD. However, more research is needed to validate the effect of NSAIDs during pregnancy on ASD and ID among children.

Leukotriene receptor antagonism with montelukast as a possible therapeutic for venous thromboembolism prophylaxis: An observational study.

BACKGROUND: Arachidonic acid (AA), which is metabolized via the cyclooxygenase (COX) and the lipoxygenase (LOX) pathways, was found to be associated with venous thromboembolism (VTE). Metabolites of the LOX pathway include cysteinyl (Cys) Leukotrienes (LT), potent proinflammatory mediators, which have also been implicated in cardiovascular disease. OBJECTIVE: The purpose of this study was to examine if cysteinyl leukotriene receptor blockade by montelukast, lowers the risk of VTE. METHODS: We conducted a retrospective cohort study examining VTE risk among COPD patients from the United States Department of Veterans Affairs. We use propensity score matching and Cox survival models to estimate the hazard ratio comparing montelukast exposure to non-exposure. Montelukast exposure was associated with a 15.9% reduction in risk of VTE compared to those unexposed (HR= 0.841; 95% CI= (0.758-0.934)). CONCLUSION: The results of this study demonstrate that targeting LTs might be beneficial for VTE prophylaxis using the clinically available LT inhibitor, montelukast. Importantly, further research on LTs is warranted to fully understand and validate this relationship.

Strategies to enhance the effects of pictorial warnings for cigarettes: results from a discrete choice experiment.

AIMS: To measure the effects of changing attributes of pictorial health warning labels (HWLs) on cigarette packs in a country that has already implemented pictorial HWLs. MEASURES: For each choice set, participants were presented with two cigarette packs and asked the following three questions: (1) 'If only these two cigarette packs were available, which would you buy?'; (2) 'Each of these two packs has warnings on the front and back about the health effects of smoking. Which of these warnings best informs you about the dangers from smoking?'; and (3) 'Which warning most makes you think about quitting smoking?'. As recommended for best practices in discrete choice experiments, each of these questions was followed by an 'opt-out' question for participants to indicate whether they really believed there was a difference between the options presented (i.e. 'Would you really choose one of them?'; 'Do you really think that either of these warnings informs you about dangers from smoking?'; or 'Do you really think that either of these warnings would make you think about quitting smoking?', respectively). Each choice set could be viewed for as long as the participant wished. For each choice question (i.e. willingness to buy, informative, motivating to quit), the pack chosen was coded as 1 and the other pack as 0, with both packs being given a value of 0 if the participant 'opted out'. DESIGN: A within-subject discrete choice experiment that involved systematic manipulation of pictorial HWL size [75 versus 30% (current policy)]; inclusion of imagery on the back of the pack [versus none (current policy)]; and color formatting [black on yellow versus yellow on black (current policy)]. SETTING: Mexico, on-line panel. PARTICIPANTS: Adult smokers (n = 705). MEASUREMENTS: For each choice set, participants selected one pack as having the most informative HWL about smoking harms, the one that makes them think the most about quitting and the one they were most willing to buy. We assessed the independent and interactive effects of HWL attributes on choices. FINDINGS: Larger HWL size on the pack front (75 versus 30%) and inclusion of a pictorial image on the pack back were both independently associated with lower willingness to buy a pack [b = -0.228, standard error (SE) = 0.023 and -0.089, SE = 0.016, respectively] and greater perception of an HWL as informative (b = 0.214, SE = 0.022, and 0.191, SE = 0.017, respectively) and motivating to quit (b = 0.251, SE = 0.023 and 0.194, SE = 0.017, respectively). HWL with black text and yellow background were perceived as less informative (b = -0.037, SE = 0.016) and less motivating to quit (b = -0.032, SE = 0.015) compared with yellow text on a black background. CONCLUSIONS: Among adult Mexican smokers, pictorial health warning labels on cigarette packages that are larger or cover both sides of the pack appear more effective at lowering purchase intentions and increasing risk perceptions and motivation to quit than smaller health warning labels or health warning labels with imagery only on the pack front.

Effect of t (11;14) Abnormality on Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the Connect MM Registry.

BACKGROUND: The t (11;14) (q13;32) translocation [t (11;14)] is present in ∼20% of patients with newly diagnosed multiple myeloma (NDMM), but studies examining its prognostic ability have yielded divergent results, and data are lacking on outcomes from first-line therapy. PATIENTS AND METHODS: Data from the Connect MM Registry, a large US, multicenter, prospective observational cohort study of patients with NDMM were used to examine the effect of t (11;14) status on first-line therapy outcomes in the Overall population (n = 1574) and race groups (African American [AA] vs. non-African American [NAA]). RESULTS: Baseline characteristics were generally similar between patients with (n = 378) and without (n = 1196) t (11;14). Prevalence of t (11;14) was similar by race (AA, 27%; NAA, 24%). In the overall population, regardless of first-line therapy, t (11;14) status did not affect progression-free survival (hazard ratio, 1.02; P = 0.7675) or overall survival (hazard ratio, 0.99; P = .9417). AA patients with t (11;14) had higher likelihood of death (Nominal Cox regression P = .0298) vs. patients without t (11;14). CONCLUSIONS: Acknowledging observational study and inferential limitations, this exploratory analysis of a predominantly community-based population suggests that t (11;14) is a neutral prognostic factor in the general MM population but may be a negative factor for overall survival in AA patients.

Leukotriene inhibition and the risk of lung cancer among U.S. veterans with asthma.

Leukotriene inhibition, in vitro and in vivo, is found to suppress tumor growth across a variety of cancer cells. A mouse model of lung cancer revealed that the leukotriene inhibitor montelukast induced lung cancer cell death. Based on the preclinical data we hypothesize that exposure to a leukotriene inhibitor is associated with a lower risk of lung cancer. We conducted a national retrospective cohort study among U.S. Veterans with asthma to explore the relationship between leukotriene inhibition and incident lung cancer. We utilize a variety of statistical techniques, including cox proportional hazards models, propensity score matching and falsification testing to examine the association. A total of 558,466 patients met study criteria consisting of 23,730 patients with leukotriene exposure and 534,736 patients with no leukotriene medication use. Leukotriene inhibitor exposure reduced the risk of lung cancer by 17% (HR = 0.830; 95% CI = (0.757-0.911)) in the unmatched and 22.2% in the matched analysis (HR = 0.778 95% CI = (0.688-0.88)). Falsification testing with appendicitis and rotator cuff injury end points, suggest no evidence of selection bias. However, because treatment was not randomized, residual confounding cannot be ruled out. The pre-clinical data on leukotriene inhibition and lung cancer combined with our database analysis provide intriguing evidence warranting further research into the relationship between leukotrienes and lung cancer.