Examining the Longitudinal Relationship Between Olfactory Dysfunction and Frailty in Community-Dwelling, older US Adults.

OBJECTIVE: Olfactory dysfunction is a "canary in the coalmine" for aging conditions. We evaluated olfactory dysfunction as a biomarker of early frailty in older adults living in the United States. STUDY DESIGN: Prospective, longitudinal, nationally representative study. SETTING: National Social Life, Health and Aging Project (NSHAP). METHODS: We examined data from 1061 community-dwelling older US adults. Odor identification (5-item Sniffin' Stick) and frailty scores were measured at baseline and 5-year follow-up. Multivariate logistic regressions evaluated the association between olfactory dysfunction and frailty at baseline in cross-section and over time in the transition from robust to prefrail to frail, adjusting for confounding factors measured at baseline. RESULTS: Older US adults who were anosmic at baseline were more likely to be frail 5 years later compared to normosmic peers (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.10-13.31, P = .035). Examining changes in frailty stage over time, we found that anosmics were more likely to transition from prefrail to frail over 5 years (OR: 3.25, 95% CI: 1.31-8.08, P = .011). Interestingly, hyposmics did not show a similar trajectory toward frailty (P > .05). In contrast, olfactory dysfunction was not associated with frailty in cross-section (OR: 0.90, 95% CI: 0.43-1.89, P = .787, hyposmia; OR: 0.72, 95% CI: 0.15-3.35, P = .673, anosmia). CONCLUSION: Older US adults with anosmia face higher odds of becoming frail over 5 years, especially those in the prefrail stage. Olfactory dysfunction may serve as a surrogate marker for early-stage neurodegenerative diseases, which are strong contributors to frailty.

Olfactory decline develops in parallel with frailty in older US adults with obstructive lung diseases.

BACKGROUND: Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases [OLDs]). Frailty and OLD's co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD. METHODS: We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physician's diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty. RESULTS: We compared individuals with OLD (n = 98; mean age 71.2 years, 59.2% women) and those without OLD (n = 1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio [OR] = 9.1, 95% confidence interval [CI] = 2.1-38.6, p = 0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR = 4.8, 95% CI = 1.3-17.5, P = 0.018; sensitivity: OR = 6.1, 95%CI = 1.2-31.0, p = 0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development. CONCLUSIONS: Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.

Social Risk and Smoking Among Women Smokers Early in the COVID-19 Pandemic: The Role of Mental Health.

Background: We examined patterns of smoking in relation to health-related socioeconomic vulnerability (HRSV) among U.S. women early in the pandemic and whether mental health symptoms mediated these relationships. Materials and Methods: Data were obtained from the April 2020 National U.S. Women's Health COVID-19 Study (N = 3200). Among current smokers, adjusted odds of increased smoking since the start of the pandemic (vs. same or less) by incident and worsening HRSVs were modeled. Structural equation modeling was used to assess anxiety, depression, and traumatic stress symptoms as mediators of the relationship between six HRSVs (food insecurity; housing, utilities, and transportation difficulties; interpersonal violence; financial strain) and increased smoking early in the pandemic. Results: Nearly half (48%) of current smokers reported increased smoking since the pandemic started. Odds of increased smoking were higher among women with incident financial strain (aOR = 2.0, 95% CI 1.2-3.3), incident food insecurity (aOR = 2.9, 95% CI 1.7-5.1), any worsening HRSV (aOR = 2.2, 95% CI 1.5-3.0), and worsening food insecurity (aOR = 1.9, 95% CI 1.3-3.0). Anxiety symptoms were a significant, partial mediator of the relationship between increased smoking and any worsening HRSVs (proportion mediated = 0.17, p = 0.001) and worsening food insecurity (0.19, p = 0.023), specifically. Depression symptoms were a significant, partial mediator of the relationship between increased smoking and any worsening HRSVs (0.15, p = 0.004) and incident financial strain (0.19, p = 0.034). Traumatic stress was not a significant mediator of any tested relationship. Conclusions: Anxiety and depression symptoms partially explain the relationship between rising socioeconomic vulnerability and increased smoking among women early in the pandemic. Addressing HRSVs and mental health may help reduce increased smoking during a public health crisis.

Utilization of an Electronic Patient-Reported Outcome Platform to Evaluate the Psychosocial and Quality-of-Life Experience Among a Community Sample of Ovarian Cancer Survivors.

PURPOSE: Novel distress screening approaches using electronic patient-reported outcome (ePRO) measurements are critical for the provision of comprehensive quality community cancer care. Using an ePRO platform, the prevalence of psychosocial factors (distress, post-traumatic growth, resilience, and financial stress) affecting quality of life in ovarian cancer survivors (OCSs) was examined. METHODS: A cross-sectional OCS sample from the National Ovarian Cancer Coalition-Illinois Chapter completed web-based clinical, sociodemographic, and psychosocial assessment using well-validated measures: Hospital Anxiety/Depression Scale-anxiety/depression, Post-traumatic Growth Inventory, Brief Resilience Scale, comprehensive score for financial toxicity, and Functional Assessment of Cancer Therapy-Ovarian (FACT-O/health-related quality of life [HRQOL]). Correlational analyses between variables were conducted. RESULTS: Fifty-eight percent (174 of 300) of OCS completed virtual assessment: median age 59 (range 32-83) years, 94.2% White, 60.3% married/in domestic partnership, 59.6% stage III-IV, 48.8% employed full-time/part-time, 55.2% had college/postgraduate education, 71.9% completed primary treatment, and median disease duration 6 (range < 1-34) years. On average, OCS endorsed normal levels of anxiety (mean ± standard deviation = 6.9 ± 3.8), depression (4.1 ± 3.6), mild total distress (10.9 ± 8.9), high post-traumatic growth (72.6 ± 21.5), normal resilience (3.7 ± 0.72), good FACT-O-HRQOL (112.6 ± 22.8), and mild financial stress (26 ± 10). Poor FACT-O emotional well-being was associated with greater participant distress (P < .001). Partial correlational analyses revealed negative correlations between FACT-O-HRQOL and anxiety (r = -0.65, P < .001), depression (r = -0.76, P < .001), and total distress (r = -0.92, P < .001). Yet, high FACT-O-HRQOL was positively correlated with post-traumatic coping (r = 0.27; P = .006) and resilience (r = 0.63; P < .001). CONCLUSION: ePRO assessment is feasible for identification of unique psychosocial factors, for example, financial toxicity and resilience, affecting HRQOL for OCS. Future investigation should explore large-scale, longitudinal ePRO assessment of the OCS psychosocial experience using innovative measures and community-based advocacy populations.

Beyond the Lung: Geriatric Conditions Afflict Community-Dwelling Older Adults With Self-Reported Chronic Obstructive Pulmonary Disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) predominantly affects older adults. However, the co-morbid occurrence of geriatric conditions has been understudied. OBJECTIVE: Characterize the prevalence of geriatric conditions among community-dwelling U.S. older adults with self-reported COPD. METHODS: We conducted a nationally representative, cross-sectional study of 3,005 U.S. community-dwelling older adults (ages 57-85 years) from the National Social Life, Health, and Aging Project (NSHAP). We evaluated the prevalence of select geriatric conditions (multimorbidity, functional disability, impaired physical function, low physical activity, modified frailty assessment, falls, polypharmacy, and urinary incontinence) and psychosocial measures (frequency of socializing, sexual activity in the last year, loneliness, cognitive impairment, and depressive symptoms) among individuals with self-reported COPD as compared to those without. Using multivariate logistic and linear regressions, we investigated the relationships between COPD and these geriatric physical and psychosocial conditions. MAIN RESULTS: Self-reported COPD prevalence was 10.7%, similar to previous epidemiological studies. Individuals with COPD had more multimorbidity [modified Charlson score 2.6 (SD 1.9) vs. 1.6 (SD 1.6)], more functional disability (58.1 vs. 29.6%; adjusted OR 3.1, 95% CI 2.3, 4.3), falls in the last year (28.4 vs. 20.8%; adjusted OR 1.4, 95% CI 1.01, 2.0), impaired physical function (75.8 vs. 56.6%; adjusted OR 2.1, 95% CI 1.1, 3.7), more frequently reported extreme low physical activity (18.7 vs. 8.1%; adjusted OR 2.3, 95% CI 1.5, 3.5) and higher frailty prevalence (16.0 vs. 2.7%; adjusted OR 6.3, 95% CI 3.0,13.0) than those without COPD. They experienced more severe polypharmacy (≥10 medications, 37.5 vs. 16.1%; adjusted OR 2.9, 95% CI 2.0, 4.2). They more frequently reported extreme social disengagement and were lonelier, but the association with social measures was eliminated when relationship status was accounted for, as those with COPD were less frequently partnered. They more frequently endorsed depressive symptoms (32.0 vs. 18.9%, adjusted OR 1.9, 95% CI 1.4, 2.7). There was no noted difference in cognitive impairment between the two populations. CONCLUSIONS: Geriatric conditions are common among community-dwelling older adults with self-reported COPD. A "beyond the lung" approach to COPD care should center on active management of geriatric conditions, potentially leading to improved COPD management, and quality of life.

Intrathecal Morphine for Analgesia in Minimally Invasive Cardiac Surgery: A Randomized, Placebo-controlled, Double-blinded Clinical Trial.

BACKGROUND: Intrathecal morphine decreases postoperative pain in standard cardiac surgery. Its safety and effectiveness have not been adequately evaluated in minimally invasive cardiac surgery. The authors hypothesized that intrathecal morphine would decrease postoperative morphine consumption after minimally invasive cardiac surgery. METHODS: In this randomized, placebo-controlled, double-blinded clinical trial, patients undergoing robotic totally endoscopic coronary artery bypass received either intrathecal morphine (5 mcg/kg) or intrathecal saline before surgery. The primary outcome was postoperative morphine equivalent consumption in the first 24 h after surgery; secondary outcomes included pain scores, side effects, and patient satisfaction. Pain was assessed via visual analog scale at 1, 2, 6, 12, 24, and 48 h after intensive care unit arrival. Opioid-related side effects (nausea/vomiting, pruritus, urinary retention, respiratory depression) were assessed daily. Patient satisfaction was evaluated with the Revised American Pain Society Outcome Questionnaire. RESULTS: Seventy-nine patients were randomized to receive intrathecal morphine (n = 37) or intrathecal placebo (n = 42), with 70 analyzed (morphine 33, placebo 37). Intrathecal morphine patients required significantly less median (25th to 75th percentile) morphine equivalents compared to placebo during first postoperative 24 h (28 [16 to 46] mg vs. 59 [41 to 79] mg; difference, -28 [95% CI, -40 to -18]; P < 0.001) and second postoperative 24 h (0 [0 to 2] mg vs. 5 [0 to 6] mg; difference, -3.3 [95% CI, -5 to 0]; P < 0.001), exhibited significantly lower visual analog scale pain scores at rest and cough at all postoperative timepoints (overall treatment effect, -4.1 [95% CI, -4.9 to -3.3] and -4.7 [95% CI, -5.5 to -3.9], respectively; P < 0.001), and percent time in severe pain (10 [0 to 40] vs. 40 [20 to 70]; P = 0.003) during the postoperative period. Mild nausea was more common in the intrathecal morphine group (36% vs. 8%; P = 0.004). CONCLUSIONS: When given before induction of anesthesia for totally endoscopic coronary artery bypass, intrathecal morphine decreases use of postoperative opioids and produces significant postoperative analgesia for 48 h.

Anxiety Shapes Expectations of Therapeutic Benefit in Phase I Trials for Patients With Advanced Cancer and Spousal Caregivers.

PURPOSE: Advanced cancer patients (ACP) hope to receive significant therapeutic benefit from phase I trials despite terminal disease and presumed symptom burdens. We examined associations between symptom burdens and expectations of therapeutic benefit for ACP and spousal caregivers (SC) during phase I trials. PATIENTS AND METHODS: A prospective cohort of ACP-SC enrolled in phase I trials was assessed at baseline and one month using symptom burden measures evaluating depression, state-trait anxiety, quality of life, global health, post-traumatic coping, and marital adjustment. Interviews evaluated expectations of benefit. RESULTS: Fifty-two phase I ACP and 52 SC (N = 104) were separately assessed and interviewed at baseline and one month. Total population demographics included the following: median age 61 years (28-78), 50% male, 100% married, 90% White, and 46% ≥ college education. At T1, ACP reported symptoms of mild state anxiety, mild trait anxiety, poor global health, and quality of life. SC reported moderate state and mild trait anxiety and good global health with little disability at baseline. State anxiety was a significant predictor of ACP expectations for phase I producing the following therapeutic benefits: stabilization (P = .01), shrinkage (P < .01), and remission (P = .04). Regression analyses also revealed negative associations between SC expectation for stabilization and SC anxiety: state (P = .01) and trait (P = .02). ACP quality of life was also negatively associated with SC expectations for stabilization (P = .02) and shrinkage (P = .01). CONCLUSION: Anxiety, both state and trait, impacts couples' beliefs regarding the likelihood of therapeutic benefit from phase I trial participation.

Olfactory Dysfunction Predicts the Development of Depression in Older US Adults.

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.

IL-1Rahigh-IL-4low-IL-13low: A Novel Plasma Cytokine Signature Associated with Olfactory Dysfunction in Older US Adults.

Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n-butanol sensitivity and odor identification, each via Sniffin' Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n-butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17) and worse odor identification (OR = 1.42, 95% CI 1.11-1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature-IL-1Rahigh-IL-4low-IL-13low-that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny.

Olfactory dysfunction persists after smoking cessation and signals increased cardiovascular risk.

BACKGROUND: Olfaction plays a critical role in health and function in older adults, and impaired sense of smell is a strong predictor of morbidity and mortality. Smoking cigarettes causes olfactory impairment, but the mechanism of damage and ability to recover after cessation are unknown. We investigated the relationship between time since quitting and olfactory dysfunction in order to elucidate the mechanism(s) by which smoking damages the olfactory system and to inform patient counseling. METHODS: Using longitudinal data from the National Social Life Health and Aging Project (n = 3528 older adults, including 1526 former smokers), we analyzed the association between odor identification performance and time since smoking cessation using multivariate ordinal logistic regression, adjusting for cognition and demographic variables. To test whether vascular disease plays a role, we also assessed the relationship between olfactory decline and incidence of heart attack and heart disease. RESULTS: Former smokers who quit ≤15 years before testing had significantly impaired olfaction compared to never smokers (p = 0.04), but those who quit >15 years prior did not. Olfactory decline over 5 years showed modest evidence toward predicting increased incidence of heart attack or heart disease (p = 0.08). CONCLUSION: Olfactory impairment in smokers persists 15 years after quitting, which is consistent with a vascular mechanism of impairment. Indeed, olfactory decline is a predictor of the development of cardiovascular disease. Taken together, these data suggest that olfactory loss may be a useful sign of underlying vascular pathology. Further investigation of olfactory loss as an early biomarker for cardiovascular disease is warranted.

Intraoperative Use of Nondepolarizing Neuromuscular Blocking Agents During Cardiac Surgery and Postoperative Pulmonary Complications: A Prospective Randomized Trial.

OBJECTIVE: Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions. DESIGN: Prospective, randomized clinical trial with blinded outcomes assessment. SETTING: University hospital, single institution. PARTICIPANTS: Adult patients having cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire. MEASUREMENTS AND MAIN RESULTS: The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02). CONCLUSION: Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications.

Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy-Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.

Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials.

PURPOSE: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. METHODS: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. RESULTS: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). CONCLUSION: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.

A Rules-Based Algorithm to Prioritize Poor Prognosis Cancer Patients in Need of Advance Care Planning.

BACKGROUND: Accurate understanding of the prognosis of an advanced cancer patient can lead to decreased aggressive care at the end of life and earlier hospice enrollment. OBJECTIVE: Our goal was to determine the association between high-risk clinical events identified by a simple, rules-based algorithm and decreased overall survival, to target poor prognosis cancer patients who would urgently benefit from advanced care planning. DESIGN: A retrospective analysis was performed on outpatient oncology patients with an index visit from April 1, 2015, through June 30, 2015. We examined a three-month window for "high-risk events," defined as (1) change in chemotherapy, (2) emergency department (ED) visit, and (3) hospitalization. Patients were followed until January 31, 2017. SETTING/SUBJECTS: A total of 219 patients receiving palliative chemotherapy at the University of Chicago Medicine with a prognosis of ≤12 months were included. MEASUREMENTS: The main outcome was overall survival, and each "high-risk event" was treated as a time-varying covariate in a Cox proportional hazards regression model to calculate a hazard ratio (HR) of death. RESULTS: A change in chemotherapy regimen, ED visit, hospitalization, and at least one high-risk event occurred in 54% (118/219), 10% (22/219), 26% (57/219), and 67% (146/219) of patients, respectively. The adjusted HR of death for patients with a high-risk event was 1.72 (95% confidence interval [CI] 1.19-2.46, p = 0.003), with hospitalization reaching significance (HR 2.74, 95% CI 1.84-4.09, p < 0.001). CONCLUSIONS: The rules-based algorithm identified those with the greatest risk of death among a poor prognosis patient group. Implementation of this algorithm in the electronic health record can identify patients with increased urgency to address goals of care.

Role of dental hardware in oral cavity squamous cell carcinoma in the low-risk nonsmoker nondrinker population.

BACKGROUND: Oral cavity squamous cell carcinoma (SCC) arising in nonsmokers and nondrinkers remains poorly characterized. We hypothesized that these patients had prior exposure to metallic dental hardware. METHODS: We utilized a questionnaire querying the lifetime oral health status of 54 patients. Demographics and extensive oral health history were collected. RESULTS: The majority of patients (74%) had prior exposure to metallic dental hardware. The younger population with almost exclusively oral tongue cancer had a high prevalence of metallic orthodontic braces (40%) within 15 years before diagnosis. In the 51+ year age group, 82% had crowns, dental implants, and/or dentures with metallic elements. CONCLUSION: Exposure to metallic dental hardware has increased in the past few decades given the rise of orthodontic braces and older adults retaining more teeth. Although this study does not prove a causal relationship between oral cavity SCC and dental hardware, this is a step toward identifying and investigating their role.

Outcomes in adolescents and young adults with Hodgkin lymphoma treated on US cooperative group protocols: An adult intergroup (E2496) and Children's Oncology Group (COG AHOD0031) comparative analysis.

BACKGROUND: There is no clear consensus between pediatric and adult providers about the treatment of adolescents and young adults (AYAs) with Hodgkin lymphoma (HL). METHODS: Failure-free survival (FFS) and overall survival (OS) were compared between 114 patients ages 17 to 21 years with HL who were treated on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Intergroup adult E2496 study and 391 similarly patients ages 17 to 21 years with HL who were treated on the pediatric Children's Oncology Group (COG) AHOD0031 study. RESULTS: Comparing AYAs from the COG and E2496 studies, there were no significant differences in extralymphatic disease, anemia, or hypoalbuminemia. More AYAs in the E2496 trial had stage III and IV disease (63% vs 29%; P < .001) and B symptoms (63% vs 27%; P < .001), and fewer had bulk disease (33% vs 77%; P < .001). More AYAs on the COG trial received radiotherapy (76% vs 66%; P = .03), although in smaller doses. E2496 AYA The 5-year FFS and OS rates were 68% and 89%, respectively in the E2496 AYAs and 81% and 97%, respectively, in the COG AYAs, indicating a statistically superior compared in the COG AYAs (P = .001). In stratified multivariable analyses, E2496 AYAs had worse FFS than COG AYAs in all strata except patients who had stage I and II HL without anemia. Propensity score analysis (based on stage, anemia, and bulk disease) confirmed inferior FFS for E2496 AYAs compared with COG AYAs (P = .004). On the E2496 study, FFS was significantly divergent across age groups (P = .005), with inferior outcomes for those ages 17 to 21 years versus 22-44 years. There was no difference across age on the COG study. CONCLUSIONS: Younger AYA patients with HL appear to have better outcomes when treated on a pediatric trial than patients of similar age on an adult trial. Prospective studies examining these differences are warranted. Cancer 2018;124:136-44. © 2017 American Cancer Society.

Global Sensory Impairment Predicts Morbidity and Mortality in Older U.S. Adults.

OBJECTIVES: To evaluate global sensory impairment (GSI, an integrated measure of sensory dysfunction) as a predictor of physical function, cognition, overall health, and mortality. DESIGN: Prospective study. SETTING: The National Social Life, Health, and Aging Project. PARTICIPANTS: A national probability sample of 3,005 home-dwelling older U.S. adults assessed at baseline (2005-06) and 5-year follow-up (2010-11). MEASUREMENTS: Gait speed, activity, disability, cognition, overall health, 5-year mortality. RESULTS: At baseline, older adults with worse GSI were slower (Timed Up and Go times: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.17-1.50) and had more activity of daily living deficits (≥2: OR = 1.26, 95% CI = 1.10-1.46). Five years later, they were still slower (timed walk: OR = 1.22, 95% CI = 1.05-1.42), had more disabilities (≥2 instrumental activities of daily living; OR = 1.45, 95% CI = 1.23-1.70), were less active (daytime activity according to accelerometry: ß = -2.7, 95% CI = -5.2 to -0.2), had worse cognitive function (Montreal Cognitive Assessment; ß = -0.64, 95% CI = -0.84 to -0.44), more likely to have poorer overall health (OR = 1.16, 95% CI = 1.03-1.31) and lose weight (>10%: OR = 1.31, 95% CI = 1.04-1.64), and have died (OR = 1.45, 95% CI = 1.19-1.76). All analyses were adjusted for relevant confounders at baseline, including age, sex, race and ethnicity, education, smoking, problem drinking, body mass index, comorbidities, and cognitive function. CONCLUSION: GSI predicts impaired physical function, cognitive dysfunction, significant weight loss, and mortality 5 years later in older U.S. adults. Multisensory evaluation may identify vulnerable individuals, offering the opportunity for early intervention to mitigate adverse outcomes.

Smoking and olfactory dysfunction: A systematic literature review and meta-analysis.

OBJECTIVES/HYPOTHESIS: A systematic review and meta-analysis of the literature was undertaken, examining the association between tobacco smoking and olfactory function in humans, utilizing PubMed and Web of Science (1970-2015) as data sources. STUDY DESIGN: Systematic literature review and meta-analysis. METHODS: This database review of studies of smoking and olfaction, with a focus on identifying high-quality studies (based on modified versions of the Newcastle-Ottawa Scale), used validated olfactory tests among the generally healthy population. RESULTS: We identified 11 studies meeting inclusion criteria. Of 10 cross-sectional studies, two were excluded from meta-analysis because the cohorts they studied were included in another article in the review. In meta-analysis, current smokers had substantially higher odds of olfactory dysfunction compared to never smokers (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.37-1.85). In contrast, former smokers were found to have no difference in risk of impaired olfaction compared to never smokers (OR = 1.05, 95% CI = 0.91-1.21). The single longitudinal study reviewed found a trend toward increased risk of olfactory decline over time in ever smokers; this trend was stronger in current as compared to former smokers. CONCLUSIONS: Current smoking, but not former smoking, is associated with significantly increased risk of olfactory dysfunction, suggesting that the effects of smoking on olfaction may be reversible. Future studies that prospectively evaluate the impact of smoking cessation on improvement in olfactory function are warranted. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:1753-1761, 2017.

Influence of pathologist experience on positive surgical margins following radical prostatectomy.

BACKGROUND: A positive surgical margin (PSM) following radical prostatectomy (RP) for prostate cancer is associated with increased risk of biochemical recurrence. We sought to examine whether the pathologist is an independent predictor of PSMs. METHODS: We performed a retrospective review of 3,557 men who underwent RP for localized prostate cancer at our institution from 2003 to 2015. We evaluated 29 separate pathologists. Univariate and multivariable logistic regression were used to test variables previously shown to influence PSM rates. RESULTS: Overall rate of PSM was 18.9%. Compared with patients without PSM, patients with PSM had higher body mass index (mean: 28.8 vs. 28.3), Gleason score≥7 (84% vs. 66%), extracapsular extension (51% vs. 20%), and median prostate-specific antigen (5.9 vs. 5.1ng/ml) (all P<0.05). Univariate logistic regression showed that surgeon experience, pathologist experience, and pathologist genitourinary fellowship training were all predictors of PSMs (all P<0.05). Multivariable regression analysis confirmed that decreased surgeon experience, increased pathologist experience, higher pathologic Gleason score, higher pathologic stage, and higher prostate-specific antigen were significant predictors of PSMs. Increasing surgeon experience was associated with decreased odds of PSM (odds ratio = 0.79 per 1 standard deviation increase, 95% CI [0.70-0.89]). In contrast, increasing pathologist experience was associated with increased odds of PSM (odds ratio = 1.11 per 1 standard deviation increase, 95% CI [1.03-1.19]). The relationship between pathologist experience and PSM appeared to be nonlinear (Fig. 2). CONCLUSIONS: Greater pathologist experience appears to be associated with greater odds of PSMs following radical prostatectomy, even after controlling for case mix, pathologist fellowship training, and surgeon experience. Based on these findings, pathologists with less experience reviewing RP specimens may consider requesting rereview by a dedicated genitourinary pathologist.

Allergy and asthma medication use in home-dwelling U.S. older adults.

BACKGROUND: Little is known about the use of allergy and asthma medications in older adults. This study aimed to assess the prevalence of use of these medications in older adults and evaluate predictors of their use. METHODS: Cross-sectional study using data from the National Social Life, Health, and Aging Project (NSHAP), a nationally representative sample of community-dwelling, U.S. adults 57 to 85 years (n = 2976) collected in 2005-2006. We determined prevalence of medication use and used logistic regression to evaluate sociodemographic and health factors associated with their use. RESULTS: Overall prevalence of allergy medication usage was 8.4% (most commonly antihistamines), and prevalence of asthma medication usage was 8.0% (most commonly bronchodilators). Allergy medication use was significantly associated with history of asthma (odds ratio [OR] 2.37; 95% confidence interval [CI], 1.52 to 3.69), chronic obstructive pulmonary disease (COPD) (OR 2.35; 95% CI, 1.58 to 3.51), or nasal surgery (OR 1.97; 95% CI, 1.00 to 3.86). Older age was associated with decreased allergy medication use (per decade, OR 0.80; 95% CI, 0.66 to 0.98). Although increased education was associated with increased overall allergy medication use, it was associated with decreased use of allergy medications generally contraindicated in the elderly. In contrast, the only significant predictors of asthma medication use were history of asthma (OR 19.66; 95% CI, 3.18 to 121.70) or COPD (OR 4.25; 95% CI, 0.88 to 20.44). CONCLUSION: Allergy and asthma medication use is prevalent among older adults and driven mostly by history of asthma or COPD. Additional sociodemographic factors predict allergy (but not asthma) medication use. Further studies are needed to evaluate efficacy of these drugs in the elderly.