Faculty Bibliography

Importance: The delivery of palliative care is not standard of care within most emergency departments (EDs). Objective: To compare quality of life, depression, health care utilization, and survival in ED patients with advanced cancer randomized to ED-initiated palliative care consultation vs care as usual. Design, Setting, and Participants: A single-blind, randomized clinical trial of ED-initiated palliative care consultation for patients with advanced cancer vs usual care took place from June 2011 to April 2014 at an urban, academic ED at a quaternary care referral center. Adult patients with advanced cancer who were able to pass a cognitive screen, had never been seen by palliative care, spoke English or Spanish, and presented to the ED met eligibility criteria; 136 of 298 eligible patients were approached and enrolled in the ED and randomized via balanced block randomization. Interventions: Intervention participants received a comprehensive palliative care consultation by the inpatient team, including an assessment of symptoms, spiritual and/or social needs, and goals of care. Main Outcomes and Measures: The primary outcome was quality of life as measured by the change in Functional Assessment of Cancer Therapy-General Measure (FACT-G) score at 12 weeks. Secondary outcomes included major depressive disorder as measured by the Patient Health Questionnaire-9, health care utilization at 180 days, and survival at 1 year. Results: A total of 136 participants were enrolled, and 69 allocated to palliative care (mean [SD], 55.1 [13.1] years) and 67 were randomized to usual care (mean [SD], 57.8 [14.7] years). Quality of life, as measured by a change in FACT-G score from enrollment to 12 weeks, was significantly higher in patients randomized to the intervention group, who demonstrated a mean (SD) increase of 5.91 (16.65) points compared with 1.08 (16.00) in controls (P = .03 using the nonparametric Wilcoxon test). Median estimates of survival were longer in the intervention group than the control group: 289 (95% CI, 128-453) days vs 132 (95% CI, 80-302) days, although this did not reach statistical significance (P = .20). There were no statistically significant differences in depression, admission to the intensive care unit, and discharge to hospice. Conclusions and Relevance: Emergency department-initiated palliative care consultation in advanced cancer improves quality of life in patients with advanced cancer and does not seem to shorten survival; the impact on health care utilization and depression is less clear and warrants further study. Trial Registration: clinicaltrials.gov Identifier: NCT01358110.

Diagnosis of type 2 diabetes and prediabetes is mandatory. Chronic hyperglycemia in diabetes is associated with long-term micro- and macrovascular as well as with neurological complications. Prediabetes predisposes patients to develop diabetes and macrovascular disease. Diagnosis of diabetes is established on (at least) one of the following criteria: a fasting plasma glucose >/= 126 mg/dl (7.0 mmol/l), a casual plasma glucose >/= 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2-h plasma glucose during the 75-g oral glucose tolerance test (OGTT) >/= 200 mg/dl (11.1 mmol/l) and/or an HbA1c >/= 6.5%. Prediabetes is defined by the Position Statement of the American Diabetes Association as a fasting plasma glucose between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0 mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%, with however some potential discordance between tests. The threshold of fasting plasma glucose defining Impaired Fasting Glucose as well as the adequacy of HbA1c as a correct diagnostic tool for prediabetes is still debated.

PURPOSE: The identification of personalized germline markers with biological relevance for the prediction of cutaneous melanoma (CM) prognosis is highly demanded but to date it has been largely unsuccessful. As melanoma progression is controlled by host immunity, here we present a novel approach interrogating immunoregulatory pathways using the genome-wide maps of expression quantitative trait loci (eQTL) to reveal biologically relevant germline variants modulating CM outcomes. EXPERIMENTAL DESIGN: Using whole genome eQTL data from a healthy population, we identified 385 variants -significantly impacting the expression of 268 immune-relevant genes. The 40 most significant eQTLs were tested in a prospective cohort of 1,221 CM patients for their association with overall (OS) and recurrence-free survival using Cox regression models. RESULTS: We identified highly significant associations with better melanoma OS for rs6673928, impacting IL19 expression (HR 0.56, 95% CI 0.41-0.77; P= 0.0002) and rs6695772, controlling the expression of BATF3 (HR 1.64, 95% CI 1.19-2.24; P= 0.0019). Both associations map in the previously suspected melanoma prognostic locus at 1q32. Furthermore, we show that their combined effect on melanoma OS is substantially enhanced reaching the level of clinical applicability (HR 1.92, 95% CI 1.43-2.60; P= 2.38e-5). CONCLUSIONS: Our unique approach of interrogating lymphocyte-specific eQTLs reveals novel and biologically relevant immunomodulatory eQTL predictors of CM prognosis that are independent of current histopathological markers. The significantly enhanced combined effect of identified eQTLs suggests the personalized utilization of both SNPs in a clinical setting, strongly indicating the promise of the proposed design for the discovery of prognostic or risk germline markers in other cancers.

INTRODUCTION: People with a mental health diagnosis have high rates of tobacco use and encounter limited availability of tobacco treatment targeted to their needs. This study compared the effectiveness of a specialized telephone smoking-cessation intervention developed for mental health patients with standard state quit-line counseling. DESIGN: RCT. SETTING/PARTICIPANTS: The study was conducted at six Veterans Health Administration facilities in the Northeast U.S. Participants were 577 mental health clinic patients referred by their providers for smoking-cessation treatment. INTERVENTION: From 2010 to 2012, the study implemented a telephone program that included patient referral from a mental health provider, mailed cessation medications, and telephone counseling. Participants were randomized to receive a specialized multisession telephone counseling protocol (n=270) or transfer to their state's quit-line for counseling (n=307). MAIN OUTCOME MEASURES: Participants completed telephone surveys at baseline, 2 months, and 6 months. The study's primary outcome was self-reported 30-day abstinence at 6 months. Secondary outcomes were self-reported 30-day abstinence, counseling satisfaction and counseling content at 2 months, and self-reported use of cessation treatment and quit attempts at 6 months. Logistic regression was used to compare treatment groups on outcomes, controlling for baseline cigarettes per day and site. Inverse probability weighting and multiple imputation were used to handle missing abstinence outcomes. Data were analyzed in 2014-2015. RESULTS: At 6 months, participants in the specialized counseling arm were more likely to report 30-day abstinence (26% vs 18%, OR=1.62, 95% CI=1.24, 2.11). There was no significant group difference in abstinence at 2 months (18% vs 14%, OR=1.31, 95% CI=0.49, 3.49). Participants in the specialized arm were more likely to be assisted with developing a quit plan; receive follow-up calls after quitting; and receive counseling on several domains, including motivation, confidence, smoking triggers, coping with urges, and mental health symptoms (all p<0.05). Specialized counseling participants were more satisfied with treatment and more likely to find the counseling useful (p<0.05). CONCLUSIONS: The specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Patients were more satisfied with the specialized counseling program. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT00724308.

AIMS: Selective vascular endothelial growth factor receptor (VEGFR) inhibitors have the potential for greater potency and less off-target toxicity compared with multikinase tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma. We carried out a meta-analysis to determine quantitatively the differences in comparative efficacy and tolerability between these newer, selective agents and the multikinase inhibitors. MATERIALS AND METHODS: We searched four electronic databases for published randomised controlled trials comparing selective VEGFR inhibitors with multikinase tyrosine kinase inhibitors for metastatic renal cell carcinoma and carried out a meta-analysis. Outcomes of interest were progression-free survival, objective response rate (ORR), overall survival, discontinuation of treatment due to adverse events (DAE) and occurrence of specific toxicities. RESULTS: Four trials involving the selective VEGFR inhibitors axitinib, tivozanib and dovitinib were analysed, all using sorafenib as the comparator. There was a 22% reduction in risk of disease progression with selective VEGFR inhibitors (relative risk 0.78; 95% confidence interval 0.69-0.87) compared with sorafenib, the tyrosine kinase inhibitor in all trials, and similar whether the agents were first-line or subsequent therapy. ORR was improved with selective VEGFR inhibitors, with 91% increased odds over sorafenib (odds ratio 1.91; 95% confidence interval 1.35-2.69). Overall survival was similar between groups (relative risk 1.03; 95% confidence interval 0.88-1.21) and DAE differed only in sensitivity analysis with exclusion of dovitinib (odds ratio 0.62; 95% confidence interval 0.41-0.94). Frequencies of the most common toxicities were overall similar, but differences included more frequent grade 3 or 4 fatigue and less frequent palmar-plantar erythrodysesthesia with selective VEGFR therapy. CONCLUSION: Although selective VEGFR inhibitors are associated with similar overall survival as multikinase inhibitor sorafenib, they show significant improvement in progression-free survival, regardless of first-line or later use, and ORR compared with sorafenib. Tolerability due to toxicities is similar.

BACKGROUND: Lymphedema is an incurable and disfiguring disease secondary to excessive fluid and protein in the interstitium as a result of lymphatic obstruction. Pneumatic compression (PC) offers a novel modality for treatment of lymphatic obstruction through targeting lymphatic beds and mimicking a functional drainage system. The objective of this study is to demonstrate improved quality of life in patients with lower-extremity lymphedema. METHODS: Consecutive patients presenting to a single institution for treatment of lymphedema were all treated with PC for at least 3 months. All patients underwent a pre- and post-PC assessment of episodes of cellulitis, number of ulcers, and venous insufficiency. Post-PC symptom questionnaires were administered. Symptom improvement was the primary outcome for analysis. RESULTS: A total of 100 patients met inclusion criteria. At presentation, 70% were female with a mean age of 57.5 years. Secondary lymphedema was present in 78%. Mean length of PC use was 12.7 months with a mean of 5.3 treatments per week. Ankle and calf limb girth decreased after PC use, (28.3 vs. 27.5 cm, P = 0.01) and (44.7 vs. 43.8 cm, P = 0.018), respectively. The number of episodes of cellulitis and ulcers pre- and post-PC decreased from mean of 0.26-0.05 episodes (P = 0.002) and 0.12-0.02 ulcers (P = 0.007), respectively. Fourteen percent had concomitant superficial venous insufficiency, all of whom underwent venous ablation. Overall 100% of patients reported symptomatic improvement post-PC with 54% greatly improved. 90% would recommend the treatment to others. CONCLUSIONS: PC improves symptom relief and reduces episodes of cellulitis and ulceration in lower-extremity lymphedema. It is well tolerated by patients and should be recommended as an adjunct to standard lymphedema therapy. Screening for venous insufficiency is recommended.

Few studies have evaluated text message (TM) content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment (OBOT) settings. This study assessed the acceptability and preferences for a tailored TM intervention in support of core OBOT medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). 97 patients enrolled in a safety net OBOT program completed a 24 item survey instrument and consisted of multiple choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving TM appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention TM during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a 'few months' into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in TM content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving TM appointment reminders, however were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a TM support system in OBOT are discussed.

BACKGROUND: Novel psychoactive substances (NPS) are emerging at an unprecedented rate. Likewise, prevalence of use and poisonings has increased in recent years. OBJECTIVE: To compare characteristics of NPS exposures and non-NPS-drug-related exposures and to examine whether there are differences between exposures involving synthetic cannabinoid receptor agonists (SCRAs) and other NPS. METHODS: Poison control center data from the five counties of New York City and Long Island were examined from 2011-2014. We examined prevalence and characteristics of NPS exposures (classified as intentional abuse) and compared characteristics of cases involving SCRAs and other NPS. RESULTS: Prevalence of NPS exposures was 7.1% in 2011, rising to 12.6% in 2014. Most exposures (82.3%) involved SCRA use. The second and third most prevalent classes were phenethylamines/synthetic cathinones ("bath salts"; 10.2%) and psychedelic phenethylamines (4.3%). Compared to other drug-related exposures (i.e. involving licit and illicit drugs), those who used NPS were more likely to be younger, male, and to have not co-used other drugs (ps < 0.001). SCRA exposures increased sharply in 2014 and the mean age of users increased over time (p < 0.01). Females exposed to SCRAs were younger than males (p < 0.001), and in 2014, individuals exposed to SCRAs were more likely to report concomitant use of alcohol than users of other NPS (p = 0.010). Users of other NPS were more likely than SCRA users to report concomitant use of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)/"Molly" (p < 0.001). CONCLUSION: Exposures reported to the poison center that involve NPS are increasing and the majority involve SCRAs. These findings should inform prevention and harm reduction approaches.

Child maltreatment is a preventable public health problem. Research has demonstrated that neighborhood structural factors (e.g. poverty, crime) can influence the proportion of a neighborhood's children who are victims of maltreatment. A newer strategy is the identification of potentially modifiable social processes at the neighborhood level that can also influence maltreatment. Toward this end, this study examines neighborhood-level data (maltreatment cases substantiated by Illinois' child protection agency, 1995-2005, social processes measured by the Project on Human Development in Chicago Neighborhoods, U.S. Census data, proportions of neighborhoods on public assistance, and crime data) that were linked across clusters of contiguous, relatively homogenous Chicago, IL census tracts with respect to racial/ethnic and socioeconomic composition. Our analysis-an ecological-level, repeated cross-sectional design utilizing random-intercept logit models-with a sensitivity analysis using spatial models to control for spatial autocorrelation-revealed consistent associations between neighborhood social processes and maltreatment. Neighborhoods higher in collective efficacy, intergenerational closure, and social networks, and lower in disorder had lower proportions of neglect, physical abuse, and sexual abuse substantiated cases, controlling for differences in structural factors. Higher collective efficacy and social network size also predicted a lower proportion of substance-exposed infants. This research indicates that strategies to mobilize neighborhood-level protective factors may decrease child maltreatment more effectively than individual and family-focused efforts alone.

BACKGROUND: Nonmedical use of opioids has become increasingly problematic in recent years with increases in overdoses, treatment admissions, and deaths. Use also appears to be contributing to heroin initiation, which has increased in recent years. Further research is needed to examine which adolescents are at highest risk for nonmedical use of opioids and heroin and to explore potential links between nonmedical opioid use and heroin use. METHODS: Data were analyzed from a nationally representative sample of American high school seniors in the Monitoring the Future study (2009-2013, Weighted N=67,822). We examined associations between frequency and recency of nonmedical use of opioids and heroin. Sociodemographic correlates of use of each drug were also examined. RESULTS: 12.4% of students reported lifetime nonmedical opioid use and 1.2% reported lifetime heroin use. As frequency of lifetime nonmedical opioid use increased, so too did the odds for reporting heroin use, with over three-quarters (77.3%) of heroin users reporting lifetime nonmedical opioid use. Recent (30-day) nonmedical opioid use was a robust risk factor for heroin use and almost a quarter (23.2%) of students who reported using opioids >/=40 times reported lifetime heroin use. Black and Hispanic students were less likely to report nonmedical opioid or heroin use than white students, but they were more likely to report heroin use in absence of nonmedical opioid use. DISCUSSION: Recent and frequent nonmedical opioid use are risk factors for heroin use among adolescents. Prevention needs to be targeted to those at highest risk.