A Financial Incentives Program to Promote Smoking Cessation Among Recently Hospitalized Individuals: Feasibility and Acceptability Study.

BACKGROUND: Hospitalization is an opportunity to engage underserved individuals in tobacco treatment who may not otherwise have access to it. Tobacco treatment interventions that begin during hospitalization and continue for at least 1 postdischarge month are effective in promoting smoking cessation. However, there is low usage of postdischarge tobacco treatment services. Financial incentives for smoking cessation are an intervention in which participants receive incentives, such as cash payments or vouchers for goods, to encourage individuals to stop smoking or to reward individuals for maintaining abstinence. OBJECTIVE: We sought to determine the feasibility and acceptability of a novel postdischarge financial incentive intervention that uses a smartphone application paired to measurements of exhaled carbon monoxide (CO) concentration levels to promote smoking cessation in individuals who smoke cigarettes. METHODS: We collaborated with Vincere Health, Inc. to tailor their mobile application that uses facial recognition features, a portable breath test CO monitor, and smartphone technology to deliver financial incentives to a participant's digital wallet after the completion of each CO test. The program includes 3 racks. Track 1: Noncontingent incentives for conducting CO tests. Track 2: Combination of noncontingent and contingent incentives for CO levels <10 parts per million (ppm). Track 3: Contingent incentives only for CO levels <10 ppm. After obtaining informed consent, we pilot-tested the program from September to November 2020 with a convenience sample of 33 hospitalized individuals at Boston Medical Center, a large safety-net hospital in New England. Participants received text reminders to conduct CO tests twice daily for 30 days postdischarge. We collected data on engagement, CO levels, and incentives earned. We measured feasibility and acceptability quantitatively and qualitatively at 2 and 4 weeks. RESULTS: Seventy-six percent (25/33) completed the program and 61% (20/33) conducted at least 1 breath test each week. Seven patients had consecutive CO levels <10 ppm during the last 7 days of the program. Engagement with the financial incentive intervention as well as in-treatment abstinence was highest in Track 3 that delivered financial incentives contingent on CO levels <10 ppm. Participants reported high program satisfaction and that the intervention helped motivate smoking cessation. Participants suggested increasing program duration to at least 3 months and adding supplemental text messaging to increase motivation to stop smoking. CONCLUSIONS: Financial incentives paired to measurements of exhaled CO concentration levels is a novel smartphone-based tobacco cessation approach that is feasible and acceptable. Future studies should examine the efficacy of the intervention after it is refined to add a counseling or text-messaging component.

Integrating Primary Care Appointments Into Resident Orientation.

BACKGROUND: Trainee well-being is a major concern for institutions and programs, yet many residents report suboptimal access to or contact with primary care for themselves. OBJECTIVE: To address the health care needs of residents, we developed a mechanism whereby all incoming residents were offered an appointment with a primary care clinician (PCP) during institutional intern orientation. METHODS: In April 2019, all incoming residents (17 specialties) were invited to participate. A collaboration involving the GME office and family medicine and internal medicine departments enabled interested residents to attend PCP appointments that were held at predesignated times during orientation and did not conflict with other orientation or learning activities. Residents received appointment details, and insurance billing processes were followed. A survey was administered to all participating PCPs and incoming residents 2 weeks following their scheduled PCP appointment. RESULTS: Of the 144 incoming residents, 118 (82%) participated. Among the 71 of 144 (49%) residents who responded to the survey, 94% indicated that they desired an appointment, with 90% attending the appointment as scheduled; 52% purposed their visit as an introduction for future appointments, while 15% requested prescription refills. All but one recommended that the initiative be offered again in the future. Seventy-two percent stated that participating in the PCP initiative definitely/probably led to improvements in self-care, and 76% indicated that participating definitely/probably made them more conscious of their health and well-being. CONCLUSIONS: Integrating PCP appointments into orientation is feasible and was highly acceptable in a large academic medical center.

Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis.

Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, ß-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.

Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles.

Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.

Intra-city Differences in Cardiac Expression of Inflammatory Genes and Inflammasomes in Young Urbanites: A Pilot Study.

Southwest Mexico City (SWMC) air pollution is characterized by high concentrations of ozone and particulate matter < 10 µm (PM(10)) containing lipopolysaccharides while in the North PM(2.5) is high. These intra-city differences are likely accounting for higher CD14 and IL-1ß in SWMC v NMC mice myocardial expression. This pilot study was designed to investigate whether similar intra-city differences exist in the levels of myocardial inflammatory genes in young people. Inflammatory mediator genes and inflammasome arrays were measured in right and left autopsy ventricles of 6 southwest/15 north (18.5 ± 2.6 years) MC residents after fatal sudden accidental deaths. There was a significant S v N right ventricle up-regulation of IL-1ß (p=0.008), TNF-α (p=0.001), IL-10 (p=0.001), and CD14 (p=0.002), and a left ventricle difference in TNF-α (p=0.007), and IL-10 (p=0.02). SW right ventricles had significant up-regulation of NLRC1, NLRP3 and of 29/84 inflammasome genes, including NOD factors and caspases. There was significant degranulation of mast cells both in myocardium and epicardial nerve fibers. Differential expression of key inflammatory myocardial genes and inflammasomes are influenced by the location of residence. Myocardial inflammation and inflammasome activation in young hearts is a plausible pathway of heart injury in urbanites and adverse effects on the cardiovascular system are expected.

Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.

Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA damage signaling, NFκB signaling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer's disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-ß (Aß) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aß plaques versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters included IL1, NFκB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down-regulation of the PrP(C) is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C) and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. Together, these data support a role for air pollution in CNS damage and its impact upon the developing brain and the potential etiology of AD and mood disorders.

Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection.

Air pollution is a serious environmental problem. Elderly subjects show increased cardiac morbidity and mortality associated with air pollution exposure. Mexico City (MC) residents are chronically exposed to high concentrations of fine particulate matter (PM(2.5)) and PM-associated lipopolysaccharides (PM-LPS). To test the hypothesis that chronic exposure to urban pollution produces myocardial inflammation, female Balb-c mice age 4 weeks were exposed for 16 months to two distinctly different polluted areas within MC: southwest (SW) and northwest (NW). SW mice were given either no treatment or chocolate 2g/9.5 mg polyphenols/3 times per week. Results were compared to mice kept in clean air. Key inflammatory mediator genes: cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the LPS receptor CD14 (cluster of differentiation antigen 14) were measured by real-time polymerase chain reaction. Also explored were target NFκB (nuclear factor κB), oxidative stress and antioxidant defense genes. TNF-α, IL-6, and COX-2 were significantly increased in both NW and SWMC mice (p=0.0001). CD14 was up-regulated in SW mice in keeping with the high exposures to particulate matter associated endotoxin. Chocolate administration resulted in a significant down-regulation of TNF-α (p<0.0001), IL-6 (p=0.01), and IL-1ß (p=0.02). The up-regulation of antioxidant enzymes and the down-regulation of potent oxidases, toll-like receptors, and pro-apoptotic signaling genes completed the protective profile. Exposure to air pollution produces up-regulation of inflammatory myocardial genes and endotoxin plays a key role in the inflammatory response. Regular consumption of dark chocolate may reduce myocardial inflammation and have cardioprotective properties in the setting of air pollution exposures.

Urban air pollution: influences on olfactory function and pathology in exposed children and young adults.

Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8+/-8.5 years were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC/25 controls 21.2+/-2.7 years. MC subjects had significantly lower UPSIT scores: 34.24+/-0.42 versus controls 35.76+/-0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE epsilon 4 carriers failed 2.4+/-0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36+/-0.16 items, p=0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid betaA(42) (29/35) and/or alpha-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration.

Immunotoxicity and environment: immunodysregulation and systemic inflammation in children.

Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.