Using Behavioral Economics to Reduce Low-Value Care Among Older Adults: A Cluster Randomized Clinical Trial.

Importance: Use of low-value care is common among older adults. It is unclear how to best engage clinicians and older patients to decrease use of low-value services. Objective: To test whether the Committing to Choose Wisely behavioral economic intervention could engage primary care clinicians and older patients to reduce low-value care. Design, Setting, and Participants: Stepped-wedge cluster randomized clinical trial conducted at 8 primary care clinics of an academic health system and a private group practice between December 12, 2017, and September 4, 2019. Participants were primary care clinicians and older adult patients who had diabetes, insomnia, or anxiety or were eligible for prostate cancer screening. Data analysis was performed from October 2019 to November 2023. Intervention: Clinicians were invited to commit in writing to Choosing Wisely recommendations for older patients to avoid use of hypoglycemic medications to achieve tight glycemic control, sedative-hypnotic medications for insomnia or anxiety, and prostate-specific antigen tests to screen for prostate cancer. Committed clinicians had their photographs displayed on clinic posters and received weekly emails with alternatives to these low-value services. Educational handouts were mailed to applicable patients before scheduled visits and available at the point of care. Main Outcomes and Measures: Patient-months with a low-value service across conditions (primary outcome) and separately for each condition (secondary outcomes). For patients with diabetes, or insomnia or anxiety, secondary outcomes were patient-months in which targeted medications were decreased or stopped (ie, deintensified). Results: The study included 81 primary care clinicians and 8030 older adult patients (mean [SD] age, 75.1 [7.2] years; 4076 men [50.8%] and 3954 women [49.2%]). Across conditions, a low-value service was used in 7627 of the 37 116 control patient-months (20.5%) and 7416 of the 46 381 intervention patient-months (16.0%) (adjusted odds ratio, 0.79; 95% CI, 0.65-0.97). For each individual condition, there were no significant differences between the control and intervention periods in the odds of patient-months with a low-value service. The intervention increased the odds of deintensification of hypoglycemic medications for diabetes (adjusted odds ratio, 1.85; 95% CI, 1.06-3.24) but not sedative-hypnotic medications for insomnia or anxiety. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial, the Committing to Choose Wisely behavioral economic intervention reduced low-value care across 3 common clinical situations and increased deintensification of hypoglycemic medications for diabetes. Use of scalable interventions that nudge patients and clinicians to achieve greater value while preserving autonomy in decision-making should be explored more broadly. Trial Registration: ClinicalTrials.gov Identifier: NCT03411525.

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under the control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed that cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium-binding proteins calbindin or calretinin, suggesting that multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2+ neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest that BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.

Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice.

The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes sleep. Infusion of a non-hydrolysable P2R agonist, ATP-γ-S, into mouse BF increased wakefulness following sleep deprivation. ATP-γ-S depolarized BF cholinergic and cortically-projecting GABAergic neurons in vitro, an effect blocked by antagonists of ionotropic P2Rs (P2XRs) or glutamate receptors. In vivo, ATP-γ-S infusion increased BF glutamate release. Thus, activation of BF P2XRs promotes glutamate release and excitation of wake-active neurons. Conversely, pharmacological antagonism of BF P2XRs decreased spontaneous wakefulness during the dark (active) period. Together with previous findings, our results suggest sleep-wake regulation by BF extracellular ATP involves a balance between excitatory, wakefulness-promoting effects mediated by direct activation of P2XRs and inhibitory, sleep-promoting effects mediated by degradation to adenosine.

A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain.

We hypothesized that adenosine, acting via the A1 receptor, is a key factor in the homeostatic control of sleep. The increase in extracellular levels of adenosine during prolonged wakefulness is thought to facilitate the transition to sleep by reducing the discharge activity of wakefulness-promoting neurons in the basal forebrain. Adenosine A1 receptor control of the homeostatic regulation of sleep was tested by microdialysis perfusion of antisense oligonucleotides against the mRNA of the A1 receptor in the magnocellular cholinergic region of the basal forebrain of freely behaving rats. After microdialysis perfusion of A1 receptor antisense in the basal forebrain, spontaneous levels of sleep-wakefulness showed a significant reduction in non-rapid eye movement (REM) sleep with an increase in wakefulness. After 6 hr of sleep deprivation, the antisense-treated animals spent a significantly reduced amount of time in non-REM sleep, with postdeprivation recovery sleep hours 2-5 showing a reduction of approximately 50-60%. There was an even greater postdeprivation reduction in delta power (60-75%) and a concomitant increase in wakefulness. All behavioral state changes returned to control (baseline) values after the cessation of antisense administration. Control experiments with microdialysis perfusion of nonsense (randomized antisense) oligonucleotides and with artificial CSF showed no effect during postdeprivation recovery sleep or spontaneously occurring behavioral states. Antisense to the A1 receptor suppressed A1 receptor immunoreactivity but did not show any neurotoxicity as visualized by Fluoro-Jade staining. These data support our hypothesis that adenosine, acting via the A1 receptor, in the basal forebrain is a key component in the homeostatic regulation of sleep.

Orexin neurons of the hypothalamus express adenosine A1 receptors.

Adenosine is a putative sleep factor with effects mainly mediated by the A1 receptor. Recent studies have implicated the hypothalamic orexin/hypocretin-containing neurons in the control of sleep-wakefulness. To help determine if adenosine might play a role in the control of orexin neurons, immunohistochemistry was used to characterize the distribution of adenosine A1 receptor protein on the orexinergic neurons. About 30% of orexin-containing neurons were labeled. The data supports the presence of adenosine A1 receptors on orexinergic neurons and suggests a possible substrate for a functional role of adenosine in the regulation of orexinergic activity.

Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative.

CONTEXT: Quality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals. OBJECTIVE: To measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI. DESIGN AND SETTING: The Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan. PATIENTS: A random sample of Medicare and non-Medicare patients at baseline (July 1998--June 1999; n = 735) and following intervention (September 1--December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January--December 1998; n = 513) and at remeasurement (March--August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group. INTERVENTION: The GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators. MAIN OUTCOME MEASURES: Differences in adherence to quality indicators (use of aspirin, beta-blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group. RESULTS: Increases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P =.02) and beta-blockers (65% vs 74%; P =.04) on admission and use of aspirin (84% vs 92%; P =.002) and smoking cessation counseling (53% vs 65%; P =.02) at discharge. For most of the other indicators, nonsignificant but favorable trends toward improvement in adherence to treatment goals were observed. Compared with the control group, Medicare patients in GAP hospitals showed a significant increase in the use of aspirin at discharge (5% vs 10%; P<.001). Use of aspirin on admission, ACE inhibitors at discharge, and documentation of smoking cessation also showed a trend for greater improvement among GAP hospitals compared with control hospitals, although none of these were statistically significant. Evidence of tool use noted during chart review was associated with a very high level of adherence to most quality indicators. CONCLUSIONS: Implementation of guideline-based tools for AMI may facilitate quality improvement among a variety of institutions, patients, and caregivers. This initial project provides a foundation for future initiatives aimed at quality improvement.