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Introduction: Over one-third of American adults have obesity with increased risk of chronic disease. Primary care providers often do not counsel patients about weight management due to barriers such as lack of time and training. To address this problem, we developed a technology-assisted health coaching intervention called Goals for Eating and Moving (GEM) to facilitate obesity counseling within the patient-centered medical home (PCMH) model of primary care. The objective of this paper is to describe the rationale and design of a cluster-randomized controlled trial to test the GEM intervention when compared to Enhanced Usual Care (EUC)., Method: We have randomized 19 PCMH teams from two NYC healthcare systems (VA New York Harbor Healthcare System and Montefiore Medical Group practices) to either the GEM intervention or EUC. Eligible participants are English and Spanish-speaking primary care patients (ages 18-69 years) with obesity or who are overweight with comorbidity (e.g., arthritis, sleep apnea, hypertension). The GEM intervention consists of a tablet-delivered goal setting tool, a health coaching visit and twelve telephone calls for patients, and provider counseling training. Patients in the EUC arm receive health education materials. The primary outcome is mean weight loss at 1 year. Secondary outcomes include changes in waist circumference, diet, and physical activity. We will also examine the impact of GEM on obesity-related provider counseling competency and attitudes., Conclusion: If GEM is found to be efficacious, it could provide a structured approach for improving weight management for diverse primary care patient populations with elevated cardiovascular disease risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Cost-effectiveness studies in randomized clinical trials have shown that tobacco cessation pharmacotherapy is among the most cost-effective of health-care interventions. Clinical trial eligibility criteria and treatment protocols may not be followed in actual practice. This study aimed to determine whether tobacco cessation pharmacotherapy is cost-effective in real-world settings., Design: A retrospective analysis of costs and outcomes., Setting: Hospitals and clinics of the US Veterans Health Administration, USA., Participants: A total of 589 862 US veterans who screened positive for tobacco use in 2011., Intervention and Comparator: Tobacco users who initiated smoking cessation pharmacotherapy in the 6 months after screening were compared with those who did not use pharmacotherapy in this period. Pharmacotherapy included nicotine replacement therapy, bupropion (if prescribed at 300 mg per day or specifically for tobacco cessation) or varenicline., Measures: Effectiveness was determined from responses to a subsequent tobacco screening conducted between 7 and 18 months after the treatment observation period. Cost of medications and prescribing health-care encounters was determined for the period between initial and follow-up tobacco use screening. Multivariate fixed-effects regression was used to assess the effect of initial treatment status on cost and outcome while controlling for differences in case-mix with propensity weighting to adjust for confounding by indication., Findings: Thirteen per cent of participants received tobacco cessation pharmacotherapy within 6 months of initial screening. After an average of an additional 218.1 days' follow-up, those who initially received pharmacotherapy incurred $143.79 in additional treatment cost and had a 3.1% absolute increase in tobacco quit rates compared with those who were not initially treated. This represents an incremental cost-effectiveness ratio of $4705 per quit. The upper limit of the 99.9% confidence region was $5600 per quit. Without propensity adjustment, the cost-effectiveness ratio was $7144 per quit, with the upper limit of the 99.9% confidence region $9500/quit., Conclusions: Tobacco cessation pharmacotherapy provided by the US Veterans Health Administration in 2011/12 was cost-effective in this real-world setting, with an incremental cost-effectiveness ratio of $4705 per quit., (© 2019 Society for the Study of Addiction.)

Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Introduction: Female veterans smoke cigarettes at high rates compared with both male veterans and nonveteran women. Proactive outreach to smokers may reduce gender disparities in cessation care. The objectives of this study were to compare baseline experiences with VA smoking cessation care for men and women and to assess for gender differences in response to a proactive outreach intervention., Methods: We conducted a post hoc subgroup analysis of a pragmatic, multisite randomized, controlled trial comparing proactive outreach with usual care (UC). Baseline experiences included physician advice to quit, satisfaction with care, and past-year treatment use. At the 1-year follow-up, treatment use, quit attempts, and 6-month prolonged abstinence for women and men randomized to proactive outreach versus UC were compared using logistic regression., Results: Baseline and follow-up surveys were returned by 138 women and 2,516 men. At baseline, women were less likely than men to report being very or somewhat satisfied with the process of obtaining smoking cessation medications in the VA (47% of women vs. 62% of men), but no less likely to report having used cessation medications from the VA in the past year (39% of women vs. 34% of men). After the intervention, phone counseling and combined therapy increased among both women and men in proactive outreach as compared with UC. At the 1-year follow-up, men in proactive outreach were significantly more likely to report prolonged abstinence than those in UC (odds ratio, 1.65; 95% CI, 1.28-2.14); results for women were in the same direction but not statistically significant (odds ratio, 1.39; 95% CI, 0.48-3.99)., Conclusions: Satisfaction with cessation care in VA remains low. Proactive outreach to smokers was associated with an increased use of cessation therapies, and increased odds of achieving prolonged abstinence. A subgroup analysis by gender did not reveal significant differences in the treatment effect., (Published by Elsevier Inc.)

Despite the high prevalence of smokeless tobacco (SLT) use in South Asia, little is known about the use of cultural smokeless tobacco among South Asians in the United States (US). This study examines the prevalence and correlates of SLT products among South Asians living in New York City (NYC). A total of 602 South Asians living in NYC completed a community health needs and resource assessment and answered questions about the use of SLT. Multivariable logistic regression models were run to examine predictors of SLT use (ever and current use). A total of 28.2% South Asian individuals reported ever use of SLT (35.9% among men and 21.5% among women) and a total of 12.9% reported current use of SLT (16.5% among men and 9.7% among women). Logistic regression models were stratified by sex. Among men, factors associated with ever or current use included: Bangladeshi and Himalayan ethnic subgroup, speaking English very well, attending a religious service a few times a year (ever use only), and current or former cigarette smoking. Among women, factors associated with ever use included: Bangladeshi ethnic subgroup, self-reporting condition of mouth and teeth as fair/poor, and at risk for depression. No factors were significant among women for current use. Overall, prevalence of current and ever use of SLT is high, and important differences exist by sex. Future studies are needed to better understand SLT use patterns in South Asian communities in the US and to inform culturally relevant interventions aiming to decrease overall tobacco use.

Introduction: Non-cigarette tobacco products are an increasing public health concern globally. Little is known about midwakh, a pipe indigenous to the United Arab Emirates (UAE). This study aimed to assess the prevalence, attitudes, behaviours and policy evaluation of midwakh smoking among 13 to 15 year olds in the UAE., Methods: We conducted secondary analyses of the 2013 UAE Global Youth Tobacco Survey. The main three outcomes were ever use, current use (past-30 days), and the number of midwakhs smoked per day. We assessed cessation, attitude, and policy measures. Regression models identified the association between each outcome measure and sex, school grade, nationality, weekly spending money, cigarette use, and parent and peer tobacco use., Results: The prevalence of ever and current midwakh use were 18.5% and 9.0%, respectively. Daily midwakh users smoked a median of 8.0 per day while non-daily users smoked 3.8 per month. Higher midwakh prevalence was reported among wealthier males, older age groups, concurrent cigarette users and among participants having peers or parents who use tobacco. There was also variation by nationality. Reduced harm perception was greater among midwakh users than non-users. About 39.6% reported being declined a midwakh purchase due to age, and 35.5% reported noticing health warnings on packages., Conclusions: Midwakh use is prevalent among 13 to 15 year olds in the UAE, and burden lies mainly with daily users. Further needed research should not delay implementation and evaluation of policies known to curb tobacco use among youth, including taxation, media campaigns, and provision of cessation services., Competing Interests: The authors have declared that no competing interests exist.

Adults ≥50 years of age have high rates of prescription opioid use. The purpose of this study is to estimate the prevalence and correlates of prescription opioid misuse among middle-aged and older adults in the United States who use prescription opioids. Data from adults age ≥ 50 from the two most recent cohorts (2015 and 2016) of the National Survey of Drug Use and Health were examined (N = 17,608). Characteristics of past-year prescription opioid misusers, including demographics, substance use, depression, chronic disease, and emergency department (ED) use, were compared to adults who used prescription opioids as prescribed in the past year and non-users. We used multivariable logistic regression to determine correlates of prescription opioid misuse among adults who used prescription opioids. Among the entire sample, 61.4% reported no past-year prescription opioid use, 36.0% reported past-year prescription opioid use without misuse, and 2.5% reported past-year prescription opioid misuse. Among past-year prescription opioid users, 6.6% reported misuse. Past-year misuse was higher among males, adults age 50-64, misusers of prescription sedatives, stimulants, and tranquilizers, users of other substances (i.e., tobacco, marijuana, cocaine), and those with alcohol use disorder. Past-year misuse was lower among adults with 2 or more chronic diseases. Past-year prescription misuse of sedatives (AOR 4.08 [95% CI 2.05-8.12]), stimulants (AOR 3.88 [95% CI 2.00-7.53]), and tranquilizers (AOR 10.02 [95% CI 6.48-15.50]) were all associated with past-year opioid misuse. Characteristics of opioid misusers determined in this study-particularly misuse of other substances-may help determine middle-aged and older adults at risk for prescription opioid misuse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar-sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugar-binding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Cell-based therapies involving the injection of adipose-derived stem/stromal cells (ASCs) within rationally designed biomaterials are a promising approach for stimulating angiogenesis. With this focus, the current work explored the effects of incorporating integrin-binding RGD or IKVAV peptides within in situ-gelling N-methacrylate glycol chitosan (MGC) hydrogels on the response of encapsulated human ASCs. Initial studies focused on hydrogel characterization to validate that the MGC, MGC-RGD, and MGC-IKVAV hydrogels had similar biomechanical properties. ASC viability following encapsulation and culture under 2% O2 was significantly impaired in the MGC-IKVAV group relative to the MGC and MGC-RGD groups. In contrast, sustained viability, along with enhanced cell spreading and metabolic activity were observed in the MGC-RGD group. Investigation of angiogenic transcription suggested that the incorporation of the peptide groups did not substantially alter the pro-angiogenic gene expression profile of the encapsulated ASCs after 7 days of culture under 2% O2. Consistent with the in vitro findings, preliminary in vivo characterization following subcutaneous implantation into NOD/SCID mice showed that ASC retention was enhanced in the MGC-RGD hydrogels relative to the MGC-IKVAV group at 14 days. Further, the encapsulated ASCs in the MGC and MGC-RGD groups promoted murine CD31 + endothelial cell recruitment to the peri-implant region. Overall, the results indicate that the MGC-RGD and MGC hydrogels are promising platforms for ASC delivery, and suggest that strategies that support long-term ASC viability can augment in vivo angiogenesis through paracrine mechanisms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 571-585, 2019., (© 2018 Wiley Periodicals, Inc.)

Cell-like hybrids from natural and synthetic amphiphiles provide a platform to engineer functions of synthetic cells and protocells. Cell membranes and vesicles prepared from human cell membranes are relatively unstable in vitro and therefore are difficult to study. The thicknesses of biological membranes and vesicles self-assembled from amphiphilic Janus dendrimers, known as dendrimersomes, are comparable. This feature facilitated the coassembly of functional cell-like hybrid vesicles from giant dendrimersomes and bacterial membrane vesicles generated from the very stable bacterial Escherichia coli cell after enzymatic degradation of its outer membrane. Human cells are fragile and require only mild centrifugation to be dismantled and subsequently reconstituted into vesicles. Here we report the coassembly of human membrane vesicles with dendrimersomes. The resulting giant hybrid vesicles containing human cell membranes, their components, and Janus dendrimers are stable for at least 1 y. To demonstrate the utility of cell-like hybrid vesicles, hybrids from dendrimersomes and bacterial membrane vesicles containing YadA, a bacterial adhesin protein, were prepared. The latter cell-like hybrids were recognized by human cells, allowing for adhesion and entry of the hybrid bacterial vesicles into human cells in vitro., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Paliperidone palmitate is a second generation antipsychotic, approved for the treatment of schizophrenia in the form of the long-acting injectable (LAI) products INVEGA SUSTENNA® (once monthly injection) and INVEGA TRINZA® (once every 3 months injection). Paliperidone palmitate dissolves slowly after deep intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The pharmacokinetic (PK) profile of the INVEGA SUSTENNA® formulation is biphasic, comprised of an initial relatively fast zero-order input, which allows rapid attainment of therapeutic concentrations without oral supplementation; and a subsequent maintained second-stage, first-order input, allowing for once monthly administration. Changes to the manufacturing processes can substantially alter the release characteristics of paliperidone palmitate LAI and consequently its PK profile. As an example, larger or smaller particle sizes of paliperidone palmitate can result in a delayed or accelerated release of paliperidone into the systemic circulation, respectively. Such changes are clinically relevant, as transient excursions above therapeutic plasma concentrations can be associated with an increased risk of adverse effects, including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms. Conversely, a delay in attaining therapeutic plasma concentrations of paliperidone on initiation of treatment, or a return to low plasma concentrations before the end of a dosing interval during repeated dosing, increases the risk of relapse. Given the integral relationship of the PK profile to the product's clinical effects, it is important to have bioequivalence standards that reflect the complexity of the paliperidone palmitate LAI PK profile if one is to consider therapeutic equivalence based on simple bioequivalence testing. Although both the EMA and U.S. FDA have product-specific guidelines to determine bioequivalence, their requirements differ substantially. In Canada, no LAI product-specific bioequivalence guidance exists for multiphasic medication delivery systems, and the recently revised Comparative Bioavailability Standards: Formulations Used for Systemic Effects guidance applies only to oral and non-injectable formulations. We recommend that new Canadian standards be developed for multiphasic and biphasic intramuscular / subcutaneous (IM/SC) products, including paliperidone palmitate LAI products, because, similar to modified-release oral dosage forms, a different PK profile in modified-release IM/SC products can result in clinically meaningful differences in safety, efficacy, and tolerability. To ensure bioequivalence for both newly initiated and switch patients, this paper proposes bioequivalence standards that could be adopted in Canada that include two studies, a multiple-dose cross-over study, and a single-dose study with partial AUC metrics.

Background: Cigarette smoking and chronic pain are prevalent, comorbid conditions with significant consequences for individuals and society. Despite overlap between smoking and chronic pain, and pain's role as a potential barrier to quitting, there are no validated interventions targeted for smokers with chronic pains (SWCPs)., Objective: To compare characteristics of urban inpatient smokers with and without chronic pain to inform the development of SWCP-targeted cessation interventions., Methods: This study reports partial results from a randomized comparative effectiveness trial of two smoking cessation interventions (NCT01363245). Participants were enrolled at two safety net hospitals in New York, NY in 2011-2014. Data were collected from the electronic health record and an interviewer-administered survey. Participants were considered to have chronic pain if they affirmed having "long-lasting, persistent, or chronic pain in the last six months" on survey., Results: Among smokers assessed for pain (n = 1093), the prevalence of chronic pain was 44%. SWCPs were more likely to report depressive symptoms and to have a history of psychiatric diagnosis (nonsubstance related) than smokers without pain. Severe problems with mobility and with performing usual activities were more common in SWCPs. No significant difference was observed in sex, race, education, nicotine dependence level, confidence in quit ability, or history of substance misuse. Conclusions/Importance: Chronic pain in smokers admitted to safety net hospitals is prevalent and associated with hindered mobility, history of psychiatric diagnosis, and prescription opioid use. Urban safety net hospitals are an appropriate setting in which to pilot SWCP-targeted cessation programs, which should be designed with consideration for patients' psychiatric history and mobility status.

Objective: To examine the association between state-level tobacco control measures and current use estimates of both e-cigarettes and cigarettes, while accounting for socio-demographic correlates., Methods: Using the 2012-2013 and 2013-2014 National Adult Tobacco Survey (NATS), we assessed prevalence estimates of US adults' e-cigarette and cigarette current use. Four state groups were created based on the combined state-specific prevalence of both products: low cigarette/e-cigarette (n = 15), high cigarette/e-cigarette (n = 16), high cigarette/low e-cigarette (n = 11), and low cigarette/high e-cigarette) (n = 9). To evaluate the implementation of state-level tobacco control measures, Tobacco Control Index (TCI) was calculated using the State of Tobacco Control annual reports for 2012 and 2013. Multinomial logistic regression models were used to examine differences among the four groups on socio-demographic factors and TCI. Low cigarette/e-cigarette group was used as the referent group., Results: Current use estimates of each product varied substantially by state; current e-cigarette use was highest in Oklahoma (10.3%) and lowest in Delaware (2.7%), and current cigarette use was highest in West Virginia (26.1%), and lowest in Vermont (12.6%). Compared to low cigarette/e-cigarette, all other US-state categories had significantly lower TCI scores (high cigarette/e-cigarette: adjusted Relative Risk Ratio [aRRR] = 0.61; 95% confidence interval [CI]: 0.60-0.61, high cigarette/low e-cigarette: aRRR = 0.74; 95% CI: 0.73-0.74, and low cigarette/high e-cigarette: aRRR = 0.72; 95% CI: 0.71-073)., Conclusions: Enforcing existing tobacco control measures likely interacts with e-cigarette use despite being cigarette-focused. Continuing to monitor e-cigarette use is critical to establish baseline use and evaluate future e-cigarette specific federal and state-level tobacco regulatory actions while accounting for the existing tobacco control environment., Implications: This study investigates state-level current use estimates of e-cigarettes and cigarettes among US adults; and their association with four existing tobacco control measures. The overall score of these measures was negatively associated with state-level current use estimates such that states with low current e-cigarette and cigarette use had the highest mean overall score. This study assesses the potential relationship between existing state-level tobacco control measures and e-cigarette use and calls for improving the enforcement of the known-to-work tobacco control measures across all US states, while developing evidence-based regulations and interventions specific to e-cigarettes within the existing US tobacco use environment.

More than 1.5 million adults in the United States use supplemental oxygen for a variety of respiratory disorders to improve their quality of life and prolong survival. This document describes recommendations from a multidisciplinary workshop convened at the ATS International Conference in 2017 with the goal of optimizing home oxygen therapy for adults. Ideal supplemental oxygen therapy is patient-specific, provided by a qualified clinician, includes an individualized prescription and therapeutic education program, and offers oxygen systems that are safe, promote mobility, and treat hypoxemia. Recently, patients and clinicians report a growing number of problems with home oxygen in the United States. Oxygen users experience significant functional, mechanical, and financial problems and a lack of education related to their oxygen equipment-problems that impact their quality of life. Health care providers report a lack of readily accessible resources needed to prescribe oxygen systems correctly and efficiently. Patients with certain lung diseases are affected more than others because of physically unmanageable or inadequate portable systems. Analysis is needed to quantify the unintended impact that the Centers for Medicare and Medicaid Services Competitive Bidding Program has had on patients receiving supplemental oxygen from durable medical equipment providers. Studies using effectiveness and implementation research designs are needed to develop and evaluate new models for patient education, identify effective ways for stakeholders to interface, determine the economic benefit of having respiratory therapists perform in-home education and follow-up testing, and collaborate with technology companies to improve portable oxygen devices. Generation of additional evidence of the benefit of supplemental oxygen across the spectrum of advanced lung diseases and the development of clinical practice guidelines should both be prioritized.

Background: Smoking is the leading preventable cause of death in the United States, but evidence-based smoking cessation therapy is underutilized. Financial incentive strategies represent an innovative approach for increasing the use of counseling and pharmacotherapy. If effective, they could supplement or supplant resource-intensive policy options, particularly in populations for whom smoking has substantial societal costs. FIESTA (Financial IncEntives for Smoking TreAtment) will randomize hospitalized smokers to receive usual smoking cessation care alone or usual smoking care augmented with financial incentives. We aim to compare the impact of these two strategies on 1) smoking abstinence, 2) use of counseling and nicotine replacement therapy, and 3) quality of life of participants. We also will evaluate the short-term and long-term return on the investment of incentives. The FIESTA Oral Microbiome Substudy will compare the oral microbiome of smokers and nonsmokers to longitudinally assess whether smoking cessation changes oral microbiome composition., Methods: We will enroll 182 inpatient participants from the Manhattan campus of the Veterans Affairs New York Harbor Healthcare System. All participants receive enhanced usual care, including screening for tobacco use, counseling while hospitalized, access to nicotine replacement therapy, and referral to a state Quitline. Patients in the financial incentive arm receive enhanced usual care and up to $550 for participating in the New York Smoker's Quitline, using nicotine replacement therapy (NRT), and achieving biochemically confirmed smoking cessation at 2 months and 6 months. In the microbiome substudy, we enroll nonsmoking control participants matched to each recruited smoker's hospital ward, sex, age, diabetes status, and antibiotic use. After discharge, participants are asked to complete periodic phone interviews at 2 weeks, 2 months, 6 months, and 12 months and provide expired carbon monoxide and saliva samples at 2 months, 6 months, and 12 months for cotinine testing and oral microbiome analysis., Discussion: The incentive interventions of FIESTA may benefit hospitalized smokers, an objective made all the more critical because smoking rates among hospitalized patients are higher than those in the general population. Moreover, the focus of FIESTA on evidence-based therapy and bioconfirmed smoking cessation can help guide policy efforts to reduce smoking-related healthcare costs in populations with high rates of tobacco use and costly illnesses., Trial Registration: ClinicalTrials.gov, NCT02506829 . Registered on 1 July 2014.

Men who have sex with men (MSM) commonly use inhaled nitrites, or poppers, though their use is a risk factor HIV seroconversion. Pre-exposure prophylaxis, or PrEP, is effective for HIV prevention, but is not widely used, and little is known regarding PrEP use and acceptability among MSM who use inhaled nitrites. We surveyed 580 MSM in Paris, France in 2016 about popper use, sexual behaviors including condomless anal intercourse (CAI), serosorting, and sexual positioning, PrEP use, PrEP candidacy, and interest in alternate PrEP delivery modalities. We included 444 HIV negative participants for the current study. 46.2% reported popper use in the prior 3 months. Using multivariate adjusted logistic regression, we found that popper users were more likely than non-users to consider themselves candidates for PrEP [adjusted relative risk ratio (aRRR) = 2.73; 95% CI 1.54-4.83], but they were not more likely to be current (aRRR = 1.54; 95% CI 0.71-3.33) or past (aRRR = 1.37; 95% CI 0.44-4.28) PrEP users. Mediation analyses indicated that increased CAI and serosorting partly explained the relationship between popper use and PrEP candidacy. There was considerable interest in alternate proposed PrEP delivery modalities, particularly long-acting injectable PrEP [adjusted risk ratio (aRR) = 1.43; 95% CI 1.15-1.79].

Adults with medical multimorbidity (≥2 chronic conditions) present challenges for health care systems to provide coordinated care. Substance use can complicate the management of chronic medical conditions, but little research has focused on the intersection of medical multimorbidity and substance use. This study uses cross-sectional analysis of 115,335 adult respondents of the 2012-2014 administrations of the National Survey on Drug Use and Health to estimate the prevalence and correlates of past-year drug use among adults with multimorbidity. The prevalence of past-year drug use was compared between individuals reporting 0, 1, and ≥2 chronic medical conditions. We used multivariable logistic regression to determine correlates of past-year drug use among adults with ≥2 chronic medical conditions. 53.1% reported no chronic conditions, 29.5% reported one chronic condition, and 17.4% reported ≥2 chronic conditions. Past-year drug use was reported by 18.3% of those with no chronic conditions, 14.8% with 1 chronic condition, and 11.6% with ≥2 chronic conditions. Cannabis and opioid analgesics (nonmedical use) were the most common drugs used across all three groups. In the adjusted model, among adults with medical multimorbidity, adults with past-year drug use were more likely to be younger, male, have lower income, and report current tobacco use, alcohol dependence, past-year depression, and having received mental health treatment in the past year. In this national cohort, fewer adults with multimorbidity reported substance use compared to adults with no or one chronic condition, however, this population with high multimorbidity may be particularly vulnerable to the negative effects of drug use.

Introduction: Veterans with mental health disorders smoke at high rates, but encounter low rates of tobacco treatment. We sought to understand barriers and facilitators to treating tobacco use in VA mental health clinics., Methods: This qualitative study was part of a trial evaluating a telephone care coordination program for smokers using mental health services at six VA facilities. We conducted semi-structured interviews with 14 staff: 12 mental health clinic staff working at the parent study's intervention sites (n = 6 psychiatrists, three psychologists, two social workers, one NP), as well as one psychiatrist and one psychologist on the VA's national tobacco advisory committee. Interviews were transcribed and inductively coded to identify themes., Results: Five "barriers" themes emerged: (1) competing priorities, (2) patient challenges/resistance, (3) complex staffing/challenging cross-discipline coordination, (4) mixed perceptions about whether tobacco is a mental health care responsibility, and (5) limited staff training/comfort in treating tobacco. Five "facilitators" themes emerged: (1) reminding mental health staff about tobacco, (2) staff belief in the importance of addressing tobacco, (3) designating a cessation medication prescriber, (4) linking tobacco to mental health outcomes and norms, and (5) limiting mental health staff burden., Conclusions: VA mental health staff struggle with knowing that tobacco use is important, but they face competing priorities, encounter patient resistance, are conflicted on their role in addressing tobacco, and lack tobacco training. They suggested strategies at multiple levels that would help overcome those barriers that can be used to design interventions that improve tobacco treatment delivery for mental health patients., Implications: This study builds upon the existing literature on the high rates of smoking, but low rates of treatment, in people with mental health diagnoses. This study is one of the few qualitative evaluations of mental health clinic staff perceptions of barriers and facilitators to treating tobacco. The study results provide a multi-level framework for developing strategies to improve the implementation of tobacco treatment programs in mental health clinics.

Introduction: There is evidence suggesting that certain subgroups of people who use tobacco do not receive tobacco pharmacology as consistently as others., Methods: This retrospective, cohort study examined the trend in the use of cessation pharmacotherapy from 2004 to 2013 using Veterans Health Administration (VHA) administrative data. Among Veterans who used tobacco in the fiscal year (FY) 2011 and had not received pharmacotherapy in the prior year, multivariable Cox regression was used to assess the independent associations between patient clinical and demographic characteristics and pharmacotherapy initiation in the 6-months follow-up period., Results: Smoking cessation pharmacotherapy in the VHA increased from 13.8% in 2004 to 25.6% in 2013. In 2011, Veterans (N = 838309) who were more likely to newly receive pharmacotherapy included those with psychiatric disorders (depression, bipolar disorder, non-alcohol substance use disorder, other anxiety, and post-traumatic stress disorder), chronic pulmonary disease, peripheral vascular disorders, and younger Veterans (adjusted rate ratios (ARRs) ranged from 1.03 to 1.92, all p < .001). Veterans less likely to receive pharmacotherapy were those with schizophrenia or other psychosis, males, Hispanics, and those with a medical condition (uncomplicated diabetes, uncomplicated hypertension, fluid and electrolyte disorders, cardiac arrhythmia, valvular disease, hypothyroidism, acquired immunodeficiency syndrome/human immunodeficiency virus, deficiency anemia, renal failure, paralysis, coagulopathy, metastatic cancer, and other neurological disorders) (ARRs ranged from 0.74 to 0.93, all p < .001)., Conclusions: Although VHA cessation pharmacotherapy use nearly doubled from 13.8% in 2004 to 25.6% in 2013, reaching undertreated subgroups, especially those with medical comorbidities, may improve cessation outcomes., Implications: Despite evidence that demographics influence the use of pharmacotherapy in smoking cessation, there is limited and contradictory information regarding how psychiatric and chronic medical illnesses affect pharmacotherapy use. Administrative data were used to determine trends and patient characteristics of those receiving pharmacotherapy to aid in smoking cessation in the Veterans Health Administration. From 2004 to 2013, pharmacotherapy use increased from 13.8% to 25.6% of current smokers. Factors associated with increased pharmacotherapy initiation were psychiatric disorders, chronic pulmonary disease, peripheral vascular disorders, and younger age. Veterans with schizophrenia or other psychosis, males, Hispanics, and most medical conditions were less likely to receive pharmacotherapy.

A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an aspartic acid [D] to asparagine [N] at position 398 of the human α5 nicotinic acetylcholine receptor subunit) has been associated with increased risk for nicotine dependence. Consequently, carriers of the risk variant may be at elevated risk for in utero nicotine exposure. To assess whether this gene-environment interaction might impact nicotine intake in developmental nicotine-exposed offspring, we utilized a mouse expressing this human SNP. D and N dams drank nicotine (100 μg/mL) in 0.2% saccharin water or 0.2% saccharin water alone (vehicle) as their sole source of fluid from 30 days prior to breeding until weaning of offspring. The nicotine (D Nic, N Nic) or vehicle (D Veh, N Veh) exposed offspring underwent a 2-bottle choice test between postnatal ages of 30 to 46 days. N Nic offspring consumed the most nicotine at the highest concentration (400 μg/mL) compared with all other groups. In contrast, D Nic offspring drank the least amount of nicotine at all concentrations tested. Nicotine-stimulated dopamine (DA) release measured from striatal synaptosomes was increased in D Nic offspring, while decreased in N Nic offspring relative to their genotype-matched controls. These data suggest that the α5 variant influences the effect of developmental nicotine exposure on nicotine intake of exposed offspring. This gene-environment interaction on striatal DA release may provide motivation for increased nicotine seeking in N Nic offspring and reduced consumption in D Nic offspring., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Importance: Prostate cancer imaging rates appear to vary by health care setting. With the recent extension of the Veterans Access, Choice, and Accountability Act, the government has provided funds for veterans to seek care outside the Veterans Health Administration (VA). It is important to understand the difference in imaging rates and subsequent differences in patterns of care in the VA vs a traditional fee-for-service setting such as Medicare., Objective: To assess the association between prostate cancer imaging rates and a VA vs fee-for-service health care setting., Design, Setting, and Participants: This cohort study included data for men who received a diagnosis of prostate cancer from January 1, 2004, through March 31, 2008, that were collected from the VA Central Cancer Registry, linked to administrate claims and Medicare utilization records, and the Surveillance, Epidemiology, and End Results Program database. Three distinct nationally representative cohorts were constructed (use of VA only, use of Medicare only, and dual use of VA and Medicare). Men older than 85 years at diagnosis and men without high-risk features but missing any tumor risk characteristic (prostate-specific antigen, Gleason grade, or clinical stage) were excluded. Analysis of the data was completed from March 2016 to February 2018., Exposures: Patient utilization of different health care delivery systems., Main Outcomes and Measures: Rates of prostate cancer imaging were analyzed by health care setting (Medicare only, VA and Medicare, and VA only) among patients with low-risk prostate cancer and patients with high-risk prostate cancer., Results: Of 98 867 men with prostate cancer (77.4% white; mean [SD] age, 70.26 [7.48] years) in the study cohort, 57.3% were in the Medicare-only group, 14.5% in the VA and Medicare group, and 28.1% in the VA-only group. Among men with low-risk prostate cancer, the Medicare-only group had the highest rate of guideline-discordant imaging (52.5%), followed by the VA and Medicare group (50.9%) and the VA-only group (45.9%) (P < .001). Imaging rates for men with high-risk prostate cancer were not significantly different among the 3 groups. Multivariable analysis showed that individuals in the VA and Medicare group (risk ratio [RR], 0.87; 95% CI, 0.76-0.98) and VA-only group (RR, 0.79; 95% CI, 0.67-0.92) were less likely to receive guideline-discordant imaging than those in the Medicare-only group., Conclusions and Relevance: The results of this study suggest that patients with prostate cancer who use Medicare rather than the VA for health care could experience more utilization of health care services without an improvement in the quality of care.

Objectives: Despite previous retrospective reports that the number of lymph nodes resected at curative intent surgery for lung cancer correlates with overall survival (OS), no consensus exists regarding the minimal nor optimal number of lymph nodes to resect at curative lung cancer surgery., Methods: We studied subjects in the Surveillance Epidemiology and End Results Database (SEER) diagnosed with non-small cell lung cancer between 2000 and 2011 who underwent either lobectomy or pneumonectomy and had pathologic negative nodal evaluation. We excluded patients with sublobar resection and/or no lymph node evaluation. We examined associations between number of lymph nodes evaluated and OS/lung cancer-specific survival by multivariable Cox regression; and predictors of evaluation of more lymph nodes., Results: Among the 33,463 patients in our sample, a median of 7 lymph nodes were evaluated. We found that lung cancer-specific survival and OS improved with increasing lymph node evaluation up to 16 to 18 lymph nodes (hazard ratio, 0.77 [95% confidence interval, 0.70-0.85] and 0.78 [95% confidence interval, 0.72-0.86], respectively). There was little additional improvement in outcomes with evaluation of >16 to 18 lymph nodes. Blacks, Hispanics, females, and patients from distinct geographical regions were less likely to have 16 or more lymph nodes evaluated., Conclusions: There was a consistently increasing survival benefit associated with a more extensive lymph node evaluation at lung cancer resection, up to 16 to 18 lymph nodes removed. The median number of nodes evaluated was, however, only 7, suggesting that setting a goal of ≥16 examined lymph nodes may lead to improved survival outcomes, and reduce disparities in care.

Background: Binge drinking among older adults has increased in the past decade. Binge drinking is associated with unintentional injuries, medical conditions, and lower health-related quality of life. No studies have characterized multimorbidity among older binge drinkers., Methods: We examined past 30-day binge alcohol use and lifetime medical conditions among adults age ≥50 from the National Survey on Drug Use and Health from 2005 to 2014. Self-reported lifetime prevalence of 13 medical conditions and medical multimorbidity (≥2 diseases) among binge drinkers were compared to non-binge drinkers. Multivariable logistic regression models were used to examine correlates of binge alcohol use among older adults with medical multimorbidity., Results: Among adults aged ≥50, 14.4% reported past-month binge drinking. Estimated prevalence of medical multimorbidity was lower (21.4%) among binge drinkers than non-binge drinkers (28.3%; p < 0.01). Binge drinkers were more likely to use tobacco and illegal drugs than non-binge drinkers (ps < 0.001). In the adjusted model, among older adults with multimorbidity, higher income (AOR = 1.44, p < 0.05), past-month tobacco use (AOR = 2.55, p < 0.001) and substance use disorder for illegal drugs (AOR = 1.80, p < 0.05) was associated with increased odds of binge alcohol use., Conclusion: The prevalence of multimorbidity was lower among current binge drinkers compared to non-binge drinkers, possibly because older adults in good health are apt to drink more than adults in poorer health. Current use of tobacco and substance use disorder were associated with an increased risk for binge drinking among older adults with multimorbidity. Binge drinking by older adults with multimorbidity may pose significant health risks especially with the concurrent use of other substances., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Acute myocardial infarction (AMI) is a major cardiovascular complication of noncardiac surgery. We aimed to evaluate the frequency, causes, and outcomes of 30-day hospital readmission after perioperative AMI., Methods: Patients who were diagnosed with AMI during hospitalization for major noncardiac surgery were identified using the 2014 US Nationwide Readmission Database. Rates, causes, and costs of 30-day readmissions after noncardiac surgery with and without perioperative AMI were identified., Results: Among 3 807 357 hospitalizations for major noncardiac surgery, 8085 patients with perioperative AMI were identified. A total of 1135 patients (14.0%) with perioperative AMI died in-hospital during the index admission. Survivors of perioperative AMI were more likely to be readmitted within 30 days than surgical patients without perioperative AMI (19.1% versus 6.5%, P <0.001). The most common indications for 30-day rehospitalization were management of infectious complications (30.0%), cardiovascular complications (25.3%), and bleeding (10.4%). In-hospital mortality during hospital readmission in the first 30 days after perioperative AMI was 11.3%. At 6 months, the risk of death was 17.6% and ≥1 hospital readmission was 36.2%., Conclusions: Among patients undergoing noncardiac surgery who develop a perioperative MI, ≈1 in 3 suffer from in-hospital death or hospital readmission in the first 30 days after discharge. Strategies to improve outcomes of surgical patients early after perioperative AMI are warranted., (© 2018 American Heart Association, Inc.)

Background: Little is known about the role of financial hardship as it relates to drug use, especially among men who have sex with men (MSM). As such, this study aimed to investigate potential associations between financial hardship status and drug use among MSM., Methods: We conducted a cross-sectional survey of 580 MSM in Paris recruited using a popular geosocial-networking smartphone application (GSN apps). Descriptive analyses and multivariate analyses were performed. A modified Poisson model was used to assess associations between financial hardship status and use of drugs (any drugs, tobacco, alcohol, marijuana, inhalant nitrites, and club drugs)., Results: In our sample, 45.5% reported that it was somewhat, very, or extremely difficult to meet monthly payments of bills (high financial hardship). In multivariate analyses, a high level of financial hardship was significantly associated with an increased likelihood of reporting use of any substance use (adjusted risk ratio [aRR] = 1.15; 95% CI = 1.05-1.27), as well as use of tobacco (aRR = 1.45; 95% CI = 1.19-1.78), marijuana (aRR = 1.48; 95% CI =1.03-2.13), and inhalant nitrites (aRR = 1.24; 95% CI = 1.03-1.50)., Conclusions: Financial hardship was associated with drug use among MSM, suggesting the need for interventions to reduce the burden of financial hardship in this population.

Lamellar to nonlamellar membrane shape transitions play essential roles in key cellular processes, such as membrane fusion and fission, and occur in response to external stimuli, including drug treatment and heat. A subset of these transitions can be modeled by means of thermally inducible amphiphile assemblies. We previously reported on mixtures of hydrogenated, fluorinated, and hybrid Janus dendrimers (JDs) that self-assemble into complex dendrimersomes (DMSs), including dumbbells, and serve as promising models for understanding the complexity of biological membranes. Here we show, by means of a variety of complementary techniques, that DMSs formed by single JDs or by mixtures of JDs undergo a thermally induced lamellar-to-sponge transition. Consistent with the formation of a three-dimensional bilayer network, we show that DMSs become more permeable to water-soluble fluorophores after transitioning to the sponge phase. These DMSs may be useful not only in modeling isotropic membrane rearrangements of biological systems but also in drug delivery since nonlamellar delivery vehicles can promote endosomal disruption and cargo release.

Introduction: Veterans with a mental health diagnosis have high rates of tobacco use but encounter low rates of treatment from providers. This study tested whether a proactive tobacco treatment approach increases treatment engagement and abstinence rates in Department of Veterans Affairs mental health patients., Study Design: RCT., Setting/participants: The study was performed from 2013 to 2017 and analyses were conducted in 2017. Investigators used the electronic medical record at four Veterans Administration facilities to identify patients documented as current smokers and who had a mental health clinic visit in the past 12 months., Intervention: Patients were mailed an introductory letter and baseline survey. Survey respondents were enrolled and randomized to intervention (n=969) or control (n=969). Control participants received a list of usual Veterans Administration smoking services. Intervention participants received a motivational outreach call, multisession telephone counseling, and assistance with obtaining nicotine replacement therapy., Main Outcome Measures: Participants completed surveys at baseline, 6 months, and 12 months after randomization. The primary outcome was self-reported 7-day abstinence from cigarettes at 12-month follow-up. Secondary outcomes included use of cessation treatment, self-reported 7-day abstinence at 6-month follow-up, and 6-month prolonged abstinence at 12-month follow-up., Results: At 12 months, intervention participants were more likely to report using telephone counseling (19% vs 3%, OR=7.34, 95% CI=4.59, 11.74), nicotine replacement therapy (47% vs 35%, OR=1.63, 95% CI=1.31, 2.03), or both counseling and nicotine replacement therapy (16% vs 2%, OR=11.93, 95% CI=6.34, 22.47). Intervention participants were more likely to report 7-day abstinence (19% vs 14%, OR=1.50, 95% CI=1.12, 2.01) and prolonged 6-month abstinence (16% vs 9%, OR=1.87, 95% CI=1.34, 2.61). After adjusting for non-ignorable missingness at follow-up, the intervention effects on 7-day and prolonged abstinence remained significant (p<0.05)., Conclusions: Proactive outreach was more effective than usual Veterans Administration care at increasing treatment engagement and long-term abstinence in mental health patients., Trial Registration: This study is registered at www.clinicaltrials.gov NCT01737281., (Published by Elsevier Inc.)

Among US men, most new prostate cancer cases are clinically localized and do not require imaging as part of staging workup according to guidelines. Two leading specialty societies promote stewardship of health resources by encouraging guideline-concordant care, thereby limiting inappropriate and obsolete imaging. However, imaging to stage low-risk prostate cancer remains high, as almost half of men with localized prostate cancer undergo wasteful imaging following diagnosis. We employed a theory-based approach, based on current evidence and data on existing practice patterns revealing that providers are the drivers to imaging decisions, to design an intervention to improve guideline -concordant prostate cancer staging imaging across populations. We conceptualized preliminary results using the theoretical domains framework and the behavior change wheel, frameworks used concurrently to investigate physicians' behaviors and intervention design in various clinical settings. Through these 2 frameworks, we designed a theory-based, physician-focused intervention to efficiently encourage guideline-concordant prostate cancer imaging, prostate cancer imaging stewardship (PCIS). Prostate cancer imaging stewardship consists of interventions (clinical order check, academic detailing, and audit and feedback) implemented at the individual, facility, and system level to enact provider behavior change by enabling facilitators and appealing to physician motivation., (Published by Elsevier Inc.)

Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH hi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDH hi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDH hi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during ex vivo expansion of UCB ALDH hi cells would prevent differentiation and expand progeny that retained pro-angiogenic functions after transplantation into non-obese diabetic/severe combined immunodeficient mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human UCB ALDH hi cells were cultured under serum-free conditions for 9 days, with or without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although total cell numbers were increased >70-fold, the frequency of cells that retained ALDH hi /CD34+ phenotype was significantly diminished under basal conditions. In contrast, DEAB-inhibition increased total ALDH hi /CD34+ cell number by ≥10-fold, reduced differentiation marker (CD38) expression, and enhanced the retention of multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB-treated cells upregulated anti-apoptotic protein expression and diminished production of proteins implicated with megakaryocyte differentiation. The i.m. transplantation of DEAB-treated cells into mice with hind-limb ischemia stimulated endothelial cell proliferation and augmented recovery of hind-limb perfusion. DEAB-inhibition of ALDH-activity delayed hematopoietic differentiation and expanded multipotent myeloid cells that accelerated vascular regeneration following i.m. transplantation in vivo. Stem Cells 2018;36:723-736., (© AlphaMed Press 2018.)

Background: Type 2 diabetes mellitus (DM) affects 9.4% of US adults and children, while another 33.9% of Americans are at risk of DM. Health care institutions face many barriers to systematically delivering the preventive care needed to decrease DM incidence. Community health workers (CHWs) may, as frontline public health workers bridging clinic and community, help overcome these challenges. This paper presents the protocol for a pragmatic, cluster-randomized trial integrating CHWs into two primary care clinics to support DM prevention for at-risk patients., Methods: The trial will randomize 15 care teams, stratified by practice site (Bellevue Hospital and Manhattan VA), totaling 56 primary care physicians. The study cohort will consist of ~ 2000 patients who are 18-75 years of age, actively enrolled in a primary care team, able to speak English or Spanish, and have at least one glycosylated hemoglobin (HbA1c) result in the prediabetic range (5.7-6.4%) since 2012. Those with a current DM diagnosis or DM medication prescription (other than metformin) are ineligible. The intervention consists of four core activities - setting health goals, health education, activation for doctor's appointments, and referrals to DM prevention programs - adjustable according to the patient's needs and readiness. The primary outcome is DM incidence. Secondary outcomes include weight loss, HbA1C, and self-reported health behaviors. Clinical variables and health behaviors will be obtained through electronic medical records and surveys, respectively. Implementation outcomes, namely implementation fidelity and physicians' perspectives about CHW integration into the clinic, will be assessed using interviews and CHW activity logs and analyzed for the influence of moderating organizational factors., Discussion: This is the first rigorous, pragmatic trial to test the effectiveness of integrating CHWs into primary care for DM prevention reaching a population-based sample. Our study's limitations include language-based eligibility and the use of HbA1c as a measure of DM risk. It will measure both clinical and implementation outcomes and potentially broaden the evidence base for CHWs and patient-centered medical home implementation. Further, the intervention's unique features, notably patient-level personalization and referral to existing programs, may offer a scalable model to benefit patients at-risk of DM., Trial Registration: Clinicaltrials.gov NCT03006666 (Received 12/27/2016).

Background: Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA., Methods: Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt., Results: A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20)., Conclusions: MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018;124:1791-7. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3'- O -sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

A promising strategy for treating peripheral ischemia involves the delivery of stem cells to promote angiogenesis through paracrine signaling. Treatment success depends on cell localization, retention, and survival within the mechanically dynamic intramuscular (IM) environment. Herein we describe an injectable, in situ-gelling hydrogel for the IM delivery of adipose-derived stem/stromal cells (ASCs), specifically designed to withstand the dynamic loading conditions of the lower limb and facilitate cytokine release from encapsulated cells. Copolymers of poly(trimethylene carbonate)-b-poly(ethylene glycol)-b-poly(trimethylene carbonate) diacrylate were used to modulate the properties of methacrylated glycol chitosan hydrogels crosslinked by thermally-initiated polymerization using ammonium persulfate and N,N,N',N'-tetramethylethylenediamine. The scaffolds had an ultimate compressive strain over 75% and maintained mechanical properties during compressive fatigue testing at physiological levels. Rapid crosslinking (<3 min) was achieved at low initiator concentration (5 mM). Following injection and crosslinking within the scaffolds, human ASCs demonstrated high viability (>90%) over two weeks in culture under both normoxia and hypoxia. Release of angiogenic and chemotactic cytokines was enhanced from encapsulated cells under sustained hypoxia, in comparison to normoxic and tissue culture polystyrene controls. When delivered by IM injection in a mouse model of hindlimb ischemia, human ASCs were well retained in the scaffold over 28 days and significantly increased the IM vascular density compared to untreated controls., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Obesity is a worldwide epidemic, and its prevalence is higher among Veterans in the United States. Based on our prior research, primary care teams at a Veterans Affairs (VA) hospital do not feel well-equipped to deliver effective weight management counseling and often lack sufficient time. Further, effective and intensive lifestyle-based weight management programs (e.g. VA MOVE! program) are underutilized despite implementation of systematic screening and referral at all VA sites. The 5As behavior change model (Assess, Advise, Agree, Assist, Arrange) is endorsed by the United States Preventive Service Task Force for use in counseling patients about weight management in primary care and reimbursed by Medicare. In this paper, we describe the iterative development of a technology-assisted intervention designed to provide primary care-based 5As counseling within Patient-Centered Medical Homes without overburdening providers/healthcare teams., Methods: Thematic analyses of prior formative work (focus groups with patients [n = 54] and key informant interviews with staff [n = 25]) helped to create a technology-assisted, health coaching intervention called Goals for Eating and Moving (GEM). To further develop the intervention, we then conducted two rounds of testing with previous formative study participants (n = 5 for Round 1, n = 5 for Round 2). Each session included usability testing of prototypes of the online GEM tool, pilot testing of 5As counseling by a Health Coach, and a post-session open-ended interview., Results: Three main themes emerged from usability data analyses: participants' emotional responses, tool language, and health literacy. Findings from both rounds of usability testing, pilot testing, as well as the open-ended interview data, were used to finalize protocols for the full intervention in the clinic setting to be conducted with Version 3 of the GEM tool., Conclusions: The use of qualitative research methods and user-centered design approaches enabled timely detection of salient issues to make iterative improvements to the intervention. Future studies will determine whether this intervention can increase enrollment in intensive weight management programs and promote clinically meaningful weight loss in both Veterans and in other patient populations and health systems.

Introduction: Individuals with (vs. without) mental illness use tobacco at higher rates and have more difficulty quitting. Treatment models for smokers with mental illness are needed., Methods: This secondary analysis of the Victory Over Tobacco study [a pragmatic randomized clinical trial (N=5123) conducted in 2009-2011 of Proactive Care (proactive outreach plus connection to smoking cessation services) vs. Usual Care] tests the effectiveness of treatment assignment in participants with and without a mental health diagnosis on population-level, 6month prolonged abstinence at one year follow-up., Results: Analyses conducted in 2015-6 found that there was no interaction between treatment group and mental health group on abstinence (F(1,3300=1.12, p=0.29)). Analyses stratified by mental health group showed that those without mental illness, assigned to Proactive Care, had a significantly higher population-level abstinence rate than those assigned to Usual Care (OR=1.40, 95% CI=1.17-1.67); in those with mental illness, assignment to Proactive Care produced a non-significant increase in abstinence compared to Usual Care (OR=1.18, 95% CI=0.98-1.41). Those with mental illness reported more medical visits, cessation advice and treatment (p<0.001), similar levels of abstinence motivation (p>0.05), but lower abstinence self-efficacy (p<0.001)., Conclusions: Those with a mental health diagnosis benefitted less from proactive outreach regarding tobacco use. VA primary care patients with mental illness may not need additional outreach because they are connected to cessation resources during medical appointments. This group may also require more intensive cessation interventions targeting self-efficacy to improve cessation rates. Clinicaltrials.gov registration # NCT00608426., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: We conducted two parallel studies evaluating the effectiveness of proactive and reactive engagement approaches to telephone treatment for smoking cessation., Methods: Patients who smoked and were interested in quitting were referred to this study and were eligible if they were current smokers and had an address and a telephone number. The data were collected at 35 Department of Veterans Affairs (VA) sites, part of four VA medical centres in both California and Nevada. In study 1, participants received multisession counselling from the California Smokers' Helpline (quitline). In study 2, they received self-help materials only. Patients were randomly assigned by week to either proactive or reactive engagement, and primary care staff were blind to this assignment. Providers gave brief advice and referred them via the electronic health record to a tobacco co-ordinator. All patients were offered cessation medications., Outcome: Using complete case analysis, in study 1 (quitline), patients in the proactive condition were more likely than those in the reactive condition to report abstinence at 6 months (21.0% vs 16.4%, p=0.03). No difference was found between conditions in study 2 (self-help) (16.9% vs 16.5%, p=0.88). Proactive outreach resulted in increased use of cessation medications in both the quitline (70.1% vs 57.6%, p<0.0001) and the self-help studies (74.5% vs 48.2%, p<0.0001)., Conclusion: Proactive outreach with quitline intervention was associated with greater long-term abstinence. Both studies resulted in high rates of medication use. Sites should use a proactive outreach approach and provide counselling whenever possible., Trial Registration Number: NCT00123682., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: To estimate the prevalence and predictors of failed biochemical verification of self-reported abstinence among participants enrolled in trials of hospital-initiated smoking cessation interventions., Design: Comparison of characteristics between participants who verified and those who failed to verify self-reported abstinence., Settings: Multi-site randomized clinical trials conducted between 2010 and 2014 in hospitals throughout the United States., Participants: Recently hospitalized smokers who reported tobacco abstinence 6 months post-randomization and provided a saliva sample for verification purposes (n = 822)., Measurements: Outcomes were salivary cotinine-verified smoking abstinence at 10 and 15 ng/ml cut-points. Predictors and correlates included participant demographics and tobacco use; hospital diagnoses and treatment; and study characteristics collected via surveys and electronic medical records., Findings: Usable samples were returned by 69.8% of the 1178 eligible trial participants who reported 7-day point prevalence abstinence. The proportion of participants verified as quit was 57.8% [95% confidence interval (CI) = 54.4, 61.2; 10 ng/ml cut-off] or 60.6% (95% CI = 57.2, 63.9; 15 ng/ml). Factors associated independently with verification at 10 ng/ml were education beyond high school education [odds ratio (OR) = 1.51; 95% CI = 1.07, 2.11], continuous abstinence since hospitalization (OR = 2.82; 95% CI = 2.02, 3.94), mailed versus in-person sample (OR = 3.20; 95% CI = 1.96, 5.21) and race. African American participants were less likely to verify abstinence than white participants (OR = 0.64; 95% CI = 0.44, 0.93). Findings were similar for verification at 15 ng/ml. Verification rates did not differ by treatment group., Conclusions: In the United States, high rates (40%) of recently hospitalized smokers enrolled in smoking cessation trials fail biochemical verification of their self-reported abstinence., (© 2017 Society for the Study of Addiction.)

Chemical and biological tools are harnessed to investigate the impact of spatial factors for functional pairing of human lectins with counterreceptors. The homodimeric adhesion/growth-regulatory galectin-1 and a set of covalently linked homo-oligomers from di- to tetramers serve as proof-of-principle test cases. Glycodendrimersomes provide a versatile and sensitive diagnostic platform to reveal thresholds for ligand density and protein concentration in aggregation assays (trans-activity), irrespective of linker length between lectin domains. Monitoring the affinity of cell binding and ensuing tumor growth inhibition reveal the linker length to be a bidirectional switch for cis-activity. The discovery that two aspects of lectin functionality (trans- versus cis-activity) respond non-uniformly to a structural change underscores the power of combining synthetic and biological tools to advance understanding of the sugar functionality of the cell surface., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Because of the rapidly increasing use of electronic cigarettes (e-cigarettes), this study aimed to investigate the individual characteristics and state-level prevalence of U.S. adults who have switched to e-cigarettes from traditional cigarettes., Methods: Data from the 2012-2013 and 2013-2014 National Adult Tobacco Surveys were analyzed in 2016. Relative percent change in switching was estimated, and the state-specific prevalence of adults who switched to e-cigarettes from traditional cigarettes was calculated and mapped. Multivariate logistic regression was conducted to examine how switching varied by sociodemographic subgroups and region., Results: Overall, the number of individuals who switched from traditional cigarettes to e-cigarettes increased by approximately 100% over the 1-year interval. Significant increases were found among a number of sociodemographics and regions. Multivariate logistic regression analyses showed that young adults and those living in the South and West were more likely to switch to e-cigarettes, compared to former smokers who did not switch. Compared with current dual users, those with higher education and those who were not single were more likely to switch to e-cigarettes. The state with the highest prevalence of switching was New Mexico (7.3%), whereas Connecticut had the lowest prevalence (0.8 %) among former smokers., Conclusions: There is an increase in the progression from traditional cigarette use to e-cigarette use. Further research is warranted to determine whether this change continues and facilitates cigarette smoking cessation as a possible public health benefit and opportunity to save lives rather than constitutes a potential threat to public health., (Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the state-specific prevalence, regional differences, and correlates of hookah use among U.S. adults., Methods: We analyzed the most recent nationally representative data of adults from the National Adult Tobacco Survey (NATS) 2012-2013 (n = 60192). State-specific prevalence of lifetime and current hookah use was calculated and mapped. Multivariate logistic regression was performed to determine the association between sociodemographic characteristics, regional differences, and hookah use., Results: Among U.S. adults (≥18 years), overall prevalence of lifetime hookah use was 12.3%, while current use was 3.9%. Mapping of state-specific prevalence revealed that the West tended to have higher rates of use, while the South tended to have lower ones. In the adjusted model, we observed that current hookah use was positively associated with younger adults, males, non-Hispanic adults, those with higher education and income statuses, being single, those living in the West, and current cigarette use., Conclusion: The prevalence of hookah use varies by state, region, and sociodemographic characteristics among adults. Future research, including longitudinal studies, are needed to identify geographic and sociodemographic characteristics and trends among hookah users, investigate hookah-related health outcomes, and evaluate targeted public health efforts aimed at this emerging threat., Implications: This study investigates state-level prevalence, regional differences, and sociodemographic characteristics of hookah use among U.S. adults, using the most recent NATS. Hookah use was positively associated with younger adults and those living in the West. This study adds to the understanding of the geographic and sociodemographic factors underlying hookah use, which can be used to develop much needed evidence-based regulations and programs that are responsive to the needs of different risk groups., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Our aim was to investigate the long-term efficacy and safety of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, added to background sulfonylurea (SU) monotherapy for patients with type 2 diabetes mellitus., Methods: The CANagliflozin cardioVascularAssessment Study (CANVAS) was a double-blind, placebo-controlled cardiovascular outcomes study that randomly assigned participants to receive placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. CANVAS included a prespecified SU substudy of patients taking background doses of SU monotherapy; data from the primary efficacy evaluation at 18 weeks have been published previously. We performed a retrospective analysis of the SU substudy at 52 weeks to measure long-term efficacy and safety of canagliflozin used with an SU. The primary objective of the long-term extension was to assess the change from baseline to 52 weeks in glycosylated hemoglobin (HbA 1c )., Findings: A total of 215 patients were included in the 52-week extension study. Patients receiving both 100-mg and 300-mg doses of canagliflozin achieved a sustained reduction in HbA 1c relative to patients receiving placebo (-0.61% [95% CI, -0.941% to -0.282%] and -0.66% [95% CI, -0.993% to -0.332%], respectively), regardless of baseline HbA 1c , duration of diabetes, SU dose, estimated glomerular filtration rate, or body mass index. A sustained reduction in fasting plasma glucose was also found in both 100-mg and 300-mg groups, relative to the placebo group (-2.04 mmol/L [95% CI, -2.778 to -1.299 mmol/L] and -1.88 mmol/L [95% CI, -2.623 to -1.146 mmol/L], respectively). Weight was reduced significantly at 52 weeks in both 100-mg and 300-mg groups, relative to placebo (-1.9% [95% CI, -3.2% to -0.7%] and -2.0% [95% CI, -3.2% to -0.7%], respectively). Reduction in systolic blood pressure was also reported for both dose groups relative to the placebo group, but there was no clear difference in HDL-C, LDL-C, or triglyceride levels. Canagliflozin was generally well tolerated. While documented hypoglycemia occurred in 14% of patients on placebo, the frequency of hypoglycemia with the addition of canagliflozin was similar. There was an increased frequency of genital mycotic infections in both men (5.1%) and women (10.4%) in both canagliflozin groups combined, relative to the placebo group (0%), and their frequency increased in the higher-dose group. There was a slightly higher rate of renal impairment in those treated with canagliflozin versus placebo (2.1% vs 0%)., Implications: After 52 weeks, patients receiving canagliflozin added to background SU had sustained reductions in HbA 1c and fasting plasma glucose, without increasing hypoglycemia and body weight; safety findings were generally consistent with the known safety profile of the drug. ClinicalTrials.gov identifier: NCT01032629., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Purpose: Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands., Methods: Through methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1-year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in-depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products., Findings: Reporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93-22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and premature loss of efficacy (shorter duration of action) was described in 98 cases (42.6%) and occurred primarily in the afternoon. Impacts on social functioning, such as disruption in work or school performance or adverse social behaviors, were found in 51 cases (22.2%)., Implications: The ~10-fold higher reporting rate of therapeutic failure with the generic product relative to its reference product in the present Canadian study resembles findings with US-marketed generic products. While these results should be interpreted with caution due to the limitations of spontaneous adverse event reporting, which may confound comparisons across products, similar findings nonetheless led the US Food and Drug Administration to declare in 2014 that 2 methylphenidate ER generic products in the United States were neither bioequivalent nor interchangeable with OROS methylphenidate-their reference product. Our results indicate a potential safety issue with the Canadian-marketed generic and suggest a need for further investigation by Health Canada., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Hospital patients with serious mental illness (SMI) have high rates of smoking. There are few post-discharge treatment models available for this population and limited research on their treatment uptake following discharge. This study is a secondary analysis of an RCT that compared multi-session intensive telephone counseling versus referral to state quitline counseling at two safety net hospitals in New York City. For this analysis, we selected all trial participants with a history of schizophrenia, schizoaffective disorder or bipolar disorder (N = 384) and used multivariable logistic regression to compare groups on self-reported 30-day abstinence at 6 months and to identify patient factors associated with use of tobacco treatment. Analyses found no significant group differences in abstinence 6 months (28% quitline vs. 29% intervention, p > 0.05), use of cessation medications (42% quitline vs. 47% intervention, p > 0.05) or receipt of at least one counseling call (47% quitline vs. 42% intervention, p > 0.05). Patients with hazardous drinking (p = 0.04) or perceived good health (p = 0.03) were less likely to use cessation medications. Homeless patients were less likely to use counseling (p = 0.02). Most patients did not use cessation treatment after discharge, and the intensive intervention did not improve abstinence rates over quitline referral. Interventions are needed to improve use of cessation treatment and long-term abstinence in patients with SMI.

Aims/hypothesis: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration., Methods: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC R ) vs nonregenerative (MSC NR ) capacity. Secreted proteins associated with islet regenerative function were identified using stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomics. To functionally validate the importance of active Wnt signalling, we stimulated the Wnt-signalling pathway in MSC NR samples during ex vivo expansion using glycogen synthase kinase 3 (GSK3) inhibition (CHIR99201), and the conditioned culture media (CM) generated was tested for the capacity to support cultured human islet cell survival and proliferation in vitro., Results: MSC R showed increased secretion of proteins associated with cell growth, matrix remodelling, immunosuppressive and proangiogenic properties. In contrast, MSC NR uniquely secreted proteins known to promote inflammation and negatively regulate angiogenesis. Most notably, MSC R maintained Wnt signalling via Wnt5A/B (~2.5-fold increase) autocrine activity during ex vivo culture, while MSC NR repressed Wnt signalling via Dickkopf-related protein (DKK)1 (~2.5-fold increase) and DKK3 secretion. Inhibition of GSK3 activity in MSC NR samples increased the accumulation of nuclear β-catenin and generated CM that augmented beta cell survival (13% increases) and proliferation when exposed to cultured human islets., Conclusions/interpretation: Maintenance of active Wnt signalling within human MSCs promotes the secretion of matricellular and proangiogenic proteins that formulate a niche for islet regeneration.

Background and Objectives: Adolescents in foster care are at high risk for cigarette smoking. However, it is not clear how their smoking behaviors vary by gender. The present study examined lifetime and current smoking among males and females, and explored gender-specific risk factors for engagement in smoking behaviors., Method: Data from the Multi Site Evaluation of Foster Youth Programs was used to evaluate patterns of smoking among adolescents aged 12-18 years (N = 1121; 489 males, 632 females)., Results: Males and females did not differ significantly in rates of lifetime and current smoking, or in the age of smoking initiation and number of cigarettes smoked on a typical day. Gender-based analyses revealed that older age and placement in group homes or residential treatment facilities were associated with heightened risk of smoking among males. In contrast, sexual minority status (i.e., nonheterosexual orientation) and increased childhood victimization were associated with heightened risk of smoking among females. A history of running away was linked to smoking in both genders., Conclusion: Gender should be considered when designing intervention programs to address cigarette smoking among foster youth, as the stressors associated with smoking may differ for males and females.

Tobacco use among young people is increasing in the United Arab Emirates, and the country is ranked 15th in the world for prevalence of type II diabetes. Expatriates comprise a majority of the population, making them an important subset to study. We aimed to test whether an educational intervention would be effective in this cultural setting. We designed 2 peer-to-peer health workshops: tobacco use and nutrition/physical activity. One workshop was randomly assigned to 18 classrooms in private schools in Abu Dhabi. Surveys were administered before and after the workshops to assess intervention effectiveness. The tobacco workshop significantly improved responses (P < 0.05). The nutrition and physical activity workshop resulted in decreased satisfaction with personal activity levels. This study provides evidence to support the national adoption of a peer-to-peer health education model as an intervention for tobacco use but not for nutrition and physical activity choices.

Background: Despite high-quality evidence demonstrating that screening reduces mortality from breast, cervical, colorectal, and lung cancers, a substantial portion of the population remains inadequately screened. There is a critical need to identify interventions that increase the uptake and adoption of evidence-based screening guidelines for preventable cancers at the community practice level. Text messaging (short message service, SMS) has been effective in promoting behavioral change in various clinical settings, but the overall impact and reach of text messaging interventions on cancer screening are unknown., Objective: The objective of this systematic review was to assess the effect of text messaging interventions on screening for breast, cervical, colorectal, and lung cancers., Methods: We searched multiple databases for studies published between the years 2000 and 2017, including PubMed, EMBASE, and the Cochrane Library, to identify controlled trials that measured the effect of text messaging on screening for breast, cervical, colorectal, or lung cancers. Study quality was evaluated using the Cochrane risk of bias tool., Results: Our search yielded 2238 citations, of which 31 underwent full review and 9 met inclusion criteria. Five studies examined screening for breast cancer, one for cervical cancer, and three for colorectal cancer. No studies were found for lung cancer screening. Absolute screening rates for individuals who received text message interventions were 0.6% to 15.0% higher than for controls. Unadjusted relative screening rates for text message recipients were 4% to 63% higher compared with controls., Conclusions: Text messaging interventions appear to moderately increase screening rates for breast and cervical cancer and may have a small effect on colorectal cancer screening. Benefit was observed in various countries, including resource-poor and non-English-speaking populations. Given the paucity of data, additional research is needed to better quantify the effectiveness of this promising intervention., (©Catherine Uy, Jennifer Lopez, Chau Trinh-Shevrin, Simona C Kwon, Scott E Sherman, Peter S Liang. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.08.2017.)

A three-component system of Janus dendrimers (JDs) including hydrogenated, fluorinated, and hybrid hydrogenated-fluorinated JDs are reported to coassemble by film hydration at specific ratios into an unprecedented class of supramolecular Janus particles (JPs) denoted Janus dendrimersomes (JDSs). They consist of a dumbbell-shaped structure composed of an onion-like hydrogenated vesicle and an onion-like fluorinated vesicle tethered together. The synthesis of dye-tagged analogs of each JD component enabled characterization of JDS architectures with confocal fluorescence microscopy. Additionally, a simple injection method was used to prepare submicron JDSs, which were imaged with cryogenic transmission electron microscopy (cryo-TEM). As reported previously, different ratios of the same three-component system yielded a variety of structures including homogenous onion-like vesicles, core-shell structures, and completely self-sorted hydrogenated and fluorinated vesicles. Taken together with the JDSs reported herein, a self-sorting pathway is revealed as a function of the relative concentration of the hybrid JD, which may serve to stabilize the interface between hydrogenated and fluorinated bilayers. The fission-like pathway suggests the possibility of fusion and fission processes in biological systems that do not require the assistance of proteins but instead may result from alterations in the ratios of membrane composition., Competing Interests: Conflict of interest statement: D.A.T. has an adjunct appointment at the University of Pennsylvania. It is not his primary affiliation.

To continue expanding the use of Single Electron Transfer-Living Radical Polymerization (SET-LRP) in applications at the interface between macromolecular science, biomacromolecules, biology and medicine, it is essential to develop novel initiators that do not compromise the structural stability of synthesized polymers in biological environments. Here, we report that stable 2-bromopropionyl peptoid-type initiators such as 1,4-bis(2-bromopropionyl)piperazine and 4-(2-bromopropionyl)morpholine are an alternative that meets the standards reached by the well-known secondary and tertiary α-haloester-type initiators in terms of excellent control over molecular weight evolution and distribution as well as polymer chain ends. SET-LRP methodologies in organic, aqueous, and biphasic organic-aqueous media were evaluated for this purpose.