Encouraging adherence in adolescents with asthma using financial incentives: An RCT.

BACKGROUND: Medication adherence in adolescents remains a significant management challenge and innovative strategies are needed to improve medication adherence. Financial incentives have been used to improve outcomes for health behaviors among adults, but have not been well-studied among adolescents. The objective of this study was to test if a modest financial incentive improved medication adherence in adolescents with asthma compared with a control group. METHODS: Participants were randomized to either control (electronic medication monitoring [EMM] with App reminders/feedback for 4 months) or intervention (EMM + $1 per day for perfect medication adherence for 3 months [maximum $84] followed by 1 month of EMM only). A repeated measures mixed model, with a first order autoregressive correlation structure between errors, was used to test the null hypothesis for an interaction of treatment group and week. RESULTS: Fifty-two participants were enrolled, and 48 completed primary analysis. Mean adherence rates declined in both groups over time, and there was no significant difference in the change in adherence rates between the groups (F-statistic = 0.72, ndf = 15, ddf = 625, p = 0.76). Adherence rates (during the 12 weeks when incentives were given) declined from 80% to 64% in the control group, and from 90% to 58% in the incentive group. There was no significant change in the slope of decline in the incentives group in the month following payment discontinuation. CONCLUSION: A modest financial incentive did not lead to significantly different medication adherence rates in adolescents with asthma who were receiving a monitoring and reminder intervention. Further study is needed to determine viable interventions to optimize medication use in this group.

Is Once Versus Twice Daily Dosing Better for Adherence in Asthma and Chronic Obstructive Pulmonary Disease?

BACKGROUND: Patients with asthma and chronic obstructive pulmonary disease (COPD) may be prescribed once- or twice-daily dosing of controller inhalers. OBJECTIVE: To assess differences in controller adherence by dosing schedule and age. METHODS: Electronic medication monitors (EMMs) captured the date and time of inhaler actuations over 90 days in patients using the Propeller Health platform. Prescribed inhaler schedule was self-reported. Once- versus twice-daily schedule comparisons were assessed retrospectively using regressions adjusting for age. RESULTS: A total of 6294 patients with asthma and 1791 patients with COPD were included. On average, once-daily users had significantly higher median (interquartile range [IQR]) daily adherence than twice-daily users (asthma: 63.3 [IQR: 31.1, 86.7]% vs 50.3 [IQR: 21.1, 78.3]%, P < .001; COPD: 83.3 [IQR: 57.2, 95.6]% vs 64.7 [IQR: 32.8, 88.9]%, P < .001). This pattern persisted in all age groups, with the exception of 4- to 17-year-olds in asthma. The lowest adherence was in the young adult population (18- to 29-year-olds). The percentage of patients who achieved ≥80% adherence was significantly higher among once- versus twice-daily users in asthma (34.3% vs 23.6%, P < .001) and COPD (54.8% vs 38.6%, P < .001). The adjusted odds of once- versus twice-daily users achieving ≥80% adherence was 1.36 (95% confidence interval: 1.19-1.56, P < .001) in asthma and 1.73 (95% confidence interval: 1.38-2.17, P < .001) in COPD. Most once-daily patients with COPD took their medication in the morning versus at night; there was no difference in morning versus afternoon/evening administration in all other asthma and COPD groups. CONCLUSION: Patients with asthma and COPD who were prescribed once-daily versus twice-daily medications were more likely to adhere to their inhalers. Patients with COPD had higher adherence than those with asthma, possibly reflecting, in part, the older cohort age. The effect of greater adherence on exacerbations is a topic for future analysis.

Impact of the natural hormonal milieu on ventral striatal responses to appetitive cigarette smoking cues: A prospective longitudinal study.

Background: The female sex hormones estradiol (E) and progesterone (P) galvanize the ventral striatal reward pathway. E elevates ventral striatal dopamine and accelerates drug-cued reinstatement, while P has opposing 'protective' effects on drug-related behavior. We hypothesize that women may exhibit greater ventral striatal responses to smoking cues (SCs) during the late follicular phase of the menstrual cycle (MC) when E is high and unimpeded by P, and reduced responses during the late luteal phase when P is high. Methods: To test our hypothesis, 24 naturally cycling cigarette-dependent women completed functional magnetic resonance (fMRI) sessions over the course of 3 MCs at select time points to reflect the early follicular (low E and P; LEP, control condition), late follicular (high E, low P; HE) and mid-luteal (high E, high P; HEP) MC phases. During fMRI sessions (counterbalanced by phase), women were exposed to a SC versus nonSC audio-visual clip. Ovulation was verified for each MC, and hormone levels were acquired prior to sessions. Results: Contrasts within conditions showed that ventral striatal brain responses to SCs versus nonSCs were negligible during LEP and greater during HE (p=0.009) and HP (p=0.016). Contrasts across conditions showed that HE and HEP had greater responses than LEP (p=0.005), and HE had greater responses than HEP (p=0.049). Conclusions: Results support and extend our retrospective cross-sectional study of the influence of the hormonal milieu on SC reactivity. Results are clinically relevant as they may guide novel, hormonally-informed and immediately translatable treatment strategies that can potentially reduce relapse in naturally cycling women.

Adherence and Self-management Interventions among Systemically Marginalized and Underserved Youth with Asthma.

Objective: Asthma disproportionately impacts youth who have been systemically marginalized and underserved, henceforth termed underserved for brevity. Disparities are driven by systemic and structural racism and social determinants of health. We aimed to synthesize findings from interventions delivered among youth who have been underserved, highlight effective intervention strategies, and provide recommendations to promote health equity. To demonstrate, we also present a case example of clinical application. Methods: We conducted a systematic literature search of randomized trials among youth (≤18 years old) who are often underserved, delivered in clinical, community, or home-based settings with medication adherence and/or self-management behaviors as an intervention outcome. We used descriptive statistics to synthesize study characteristics and outcomes. Results: Twenty four articles, representing 21 unique interventions, met inclusion criteria. Forty-six percent reported significant improvements in adherence or self-management for the intervention group. Self-management interventions focused on symptom recognition and monitoring demonstrated the greatest percentage of significant intervention findings (71.4%); controller medication adherence interventions demonstrated the fewest (33.3%). Conclusions: Interventions are not consistently effective for youth who have been underserved. Findings suggest that pediatric psychologists can help patients from underserved backgrounds by bolstering symptom recognition and monitoring skills, providing self-management skill education, and problem-solving ways to reduce triggers through individually tailored, multicomponent approaches. Pediatric psychologists should simultaneously strive to consider and address systemic, structural, and social determinants of asthma disparities in their work.

Biologics for Asthma and Allergic Skin Diseases in Children.

An estimated 7 million children in the United States have asthma, which causes a significant health care burden and affects quality of life. The minority of these children have asthma that does not respond to Global Initiative for Asthma steps 4 and 5 care, and biological medications are recommended at this level in the 2019 Global Initiative for Asthma recommendations. In addition, biologics have been introduced into the care of children with allergic skin diseases. Omalizumab and mepolizumab are approved for children as young as 6 years, and benralizumab and dupilumab are approved for people aged ≥12 years. Reslizumab is approved only for people aged ≥18 years. These monoclonal antibodies may be added for appropriate patients when asthma or allergic skin diseases are not well controlled. Pediatricians and pediatric subspecialists should work together and be aware of the benefits and risks of these medications for their patients, as well as the practical implications of providing these options for their patients. This clinical report serves as an evaluation of the current literature on these types of medications in the treatment of children with asthma and allergic skin disease.

Exploration of the influence of body mass index on intra-network resting-state connectivity in chronic cigarette smokers.

BACKGROUND: Obesity and cigarette smoking are two leading preventable causes of death. Previous research suggests that comorbid smoking and obesity likely share neurobehavioral underpinnings; however, the influence of body mass index (BMI) on resting-state functional connectivity (rsFC) in smokers remains unknown. In this study, we explore how BMI affects rsFC and associations between rsFC and smoking-related behavior. METHODS: Treatment-seeking cigarette smokers (N = 87; 54 % men) completed a BOLD resting-state fMRI scan session. We grouped smokers into BMI groups (N = 23 with obesity, N = 33 with overweight, N = 31 lean) and used independent components analysis (ICA) to identify the resting state networks commonly associated with cigarette smoking: salience network (SN), right and left executive control networks (ECN) and default mode network (DMN). Average rsFC values were extracted (p < 0.001, k = 100) to determine group differences in rsFC and relationship to self-reported smoking and dependence. RESULTS: Analyses revealed a significant relationship between BMI and connectivity in the SN and a significant quadratic effect of BMI on DMN connectivity. Heavier smoking was related to greater rsFC in the SN among lean and obese groups but reduced rsFC in the overweight group. CONCLUSIONS: Findings build on research suggesting an influence of BMI on the neurobiology of smokers. In particular, dysfunction of SN-DMN-ECN circuitry in smokers with overweight may lead to a failure to modulate attention and behavior and subsequent difficulty quitting smoking. Future research is needed to elucidate the mechanism underlying the interaction of BMI and smoking and its impact on treatment.

Influence of the natural hormonal milieu on brain and behavior in women who smoke cigarettes: Rationale and methodology.

Women experience more severe health consequences from smoking, have greater difficulty quitting, and respond less favorably to nicotine replacement therapy than men. The influence of fluctuating ovarian hormones, specifically estradiol (E) and progesterone (P), on brain and behavioral responses during exposure to smoking reminders (i.e., cues) may be a contributing factor. Results from our laboratory suggest that women in the late follicular phase of their menstrual cycle (MC) have enhanced smoking cue (SC) vulnerabilities and reduced functional connectivity in neurocircuitry underlying cognitive control, potentially placing them at greater risk for continued smoking and relapse. The primary aim of this study is to examine and link hormonal status with brain and behavioral responses to SCs over the course of three monthly MCs in naturally cycling women who are chronic cigarette smokers. This longitudinal, counterbalanced study collects brain and behavioral responses to SCs at three time points during a woman's MC. Participants complete psychological and physical examinations, biochemical hormonal verification visits, and at least three laboratory/neuroimaging scan visits. The scan visits include a 10-min SC task during blood oxygen level-dependent (BOLD) data acquisition and are timed to occur during the early follicular phase (low E and P), late follicular phase (high E, unopposed by P), and mid-luteal phase (high P, high E). The primary outcomes include brain responses to SCs (compared to non-SCs), subjective craving, E and P hormone levels, and behavioral responses to SCs. This study addresses a critical gap in our knowledge: namely, the impact of the natural hormonal milieu on brain and behavioral responses to SCs, a powerful relapse trigger. Additionally, this study will provide a roadmap for human sex differences researchers who are obliged to consider the often confounding cyclic hormonal fluctuations of women.

Smoking-induced craving relief relates to increased DLPFC-striatal coupling in nicotine-dependent women.

BACKGROUND: Craving is a major contributor to drug-seeking and relapse. Although the ventral striatum (VS) is a primary neural correlate of craving, strategies aimed at manipulating VS function have not resulted in efficacious treatments. This incongruity may be because the VS does not influence craving in isolation. Instead, craving is likely mediated by communication between the VS and other neural substrates. Thus, we examined how striatal functional connectivity (FC) with key nodes of networks involved in addiction affects relief of craving, which is an important step in identifying viable treatment targets. METHODS: Twenty-four nicotine-dependent non-abstinent women completed two resting-state (rs) fMRI scans, one before and one following smoking a cigarette in the scanner, and provided craving ratings before and after smoking the cigarette. A seed-based approach was used to examine rsFC between the VS, putamen and germane craving-related brain regions; the dorsolateral prefrontal cortex (dlPFC), the posterior cingulate cortex, and the anterior ventral insula. RESULTS: Smoking a cigarette was associated with a decrease in craving. Relief of craving correlated with increases in right dlPFC- bilateral VS (r = 0.57, p = 0.003, corrected) as did increased right dlPFC-left putamen coupling (r = 0.62, p = 0.001, corrected). CONCLUSIONS: Smoking-induced relief of craving is associated with enhanced rsFC between the dlPFC, a region that plays a pivotal role in decision making, and the striatum, the neural structure underlying motivated behavior. These findings are highly consistent with a burgeoning literature implicating dlPFC-striatal interactions as a neurobiological substrate of craving.

An exploration of associations between smoking motives and behavior as a function of body mass index.

Objective: Cigarette smoking and obesity are the leading causes of premature morbidity and mortality and increase the risk of all-cause mortality four-fold when comorbid. Although research suggests that smoking motives may differ based on body mass index (BMI), it is unclear how these differences translate to smoking behavior. Method: Three groups of adults who smoke cigarettes (N = 79; obese n = 25, overweight n = 30, and lean n = 24) completed measures of smoking and the Smoking Motivations Questionnaire. Groups did not differ on age, education, cigarettes per day (CPD), pack-years, or nicotine dependence, as measured by the Fagerström Test for Cigarette Dependence (FTCD). Results: Analyses revealed different associations between reasons for smoking and smoking behavior depending on lean, overweight, or obesity status. Participants (N = 37 female, average age 39.8 years) self-reported smoking was positively associated with Addictive, and Automatic subscale scores among lean participants, with only the Addictive subscale score among those with overweight, and only the Automatic subscale score among those with obesity. Post hoc MANCOVA analysis revealed a significant interaction effect of Group x Automatic Smoking on Pack-years (F(2, 79)=3.34, p = 0.04). Conclusion: Findings suggest smoking motives are differentially associated with smoking behavior in adults who smoke depending on weight status. The daily smoking rate of participants with obesity may be less related to the addictive quality of smoking, and automaticity may be less associated with smoking history in those with overweight. Additional research on the influence of BMI on cigarette smoking is necessary to fully elucidate how obesity may impact treatment outcomes to optimize smoking cessation treatment among those with excess body weight.

Electronic medication monitors help determine adherence subgroups in asthma.

Non-adherence to treatment regimens in asthma is well described, however less is known about temporal patterns of medication use. We monitored 20 weeks of controller medication use and analyzed these patterns in patients ≥4 years of age with self-reported asthma enrolled in a digital health program. At baseline, approximately 20%, 28%, 25% and 27% of patients had optimal, moderate, sub-optimal and poor adherence, respectively. Medication adherence decreased in all groups in this study. The largest absolute decreases in adherence (-32%) were observed for moderately adherent patients. Certain adherence patterns which demonstrated greater declines, that, once identified, could be intervened upon.

They just don't take their medicines: Reframing medication adherence in asthma from frustration to opportunity.

Assessing and addressing suboptimal adherence to asthma medications is a key component in the treatment of all children with asthma, particularly those with difficult-to-treat asthma. However, parents often overreport adherence to asthma medications. Increased medication adherence could lead to improved outcomes in the form of better asthma control and decreased asthma exacerbations, as well as decreased healthcare utilization costs. Yet there are many complex factors that affect medication adherence, and barriers are often different in each family. Social determinants of health, complex healthcare relationships, and patient-related factors may all affect medication adherence. Multicomponent patient-centered strategies, as well as strategies that utilize technology and habit formation strategies may be helpful in improving medication adherence. Further study is needed to reliably and sustainably improve medication adherence in children with asthma across the broader population; in some populations, alternate diagnoses, adjusting therapy, and other intervention may be required to improve asthma control and health.

Asthma attacks in children are always preceded by poor asthma control: myth or maxim?

Some, but not all, asthma exacerbations in children are preceded by poor asthma control https://bit.ly/3muIy6h.

Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation.

We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and selective CDK2 inhibitors. The discovery of this new class of ATP-site directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis of new medicinal chemistry tool in search for an effective treatment of cancer and other diseases that involve protein kinase signaling pathways.

The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines.

The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2-a]pyridine nucleus. In this report, we describe the first successful use of this class of aza-heterocycles to generate potent inhibitors of cyclin-dependent kinases that compete with ATP for binding to a catalytic subunit of the protein. Co-crystal structures of CDK2 in complex with lead compounds reveal a unique mode of binding. Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways.