Reimbursement Incentives to Improve Adherence to Follow-Up of Cervical Cancer Cytology Screening Results in Peru.

OBJECTIVE: The purpose of this study was to determine Peruvian women's attitudes toward novel reimbursement incentives used to improve adherence to obtaining cervical cytology test results. MATERIALS AND METHODS: Women presenting for cervical cancer screening in Peru completed a 34-item Investigational Review Board-approved questionnaire. The questionnaire determined their attitudes toward various reimbursement incentives to improve adherence to obtaining cervical cytology results. Descriptive statistics, generalized linear models, and Kruskal-Wallis tests were used in the analyses. RESULTS: Completed questionnaires were available for 997 women. Most women (51%) would be more likely to return for their Pap result if an incentive was provided, 79% (759/956) agreed that they would pay for the Pap test, and 51% (402/859) would be willing to pay 10 Soles or less. Quechua-speaking women considered follow-up more difficult (p < .0001) but were less likely to return for their Pap results (p < .0001), pay for the Pap test (p < .0001), and afford paying more than 5 Soles (p < .0001) than women who spoke Spanish or both languages. More women who earn 1000 Soles/year or less would likely return if incentivized (p < .0001), felt the incentive would help them remember to return (p = .0047), and would be willing to pay whether there was a rebate (p = .010) as compared with women earning more money. CONCLUSIONS: A reimbursement incentive program designed to improve follow-up of cervical cytology test results was acceptable to most Peruvian women. Such a behavioral-modifying program may improve patient follow-up after cervical cytology testing. Implementation may reduce the morbidity and mortality of cervical cancer in remote regions of the country.

Dorsal BNST α2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors.

Stress is a precipitating agent in neuropsychiatric disease and initiates relapse to drug-seeking behavior in addicted patients. Targeting the stress system in protracted abstinence from drugs of abuse with anxiolytics may be an effective treatment modality for substance use disorders. α2A-adrenergic receptors (α2A-ARs) in extended amygdala structures play key roles in dampening stress responses. Contrary to early thinking, α2A-ARs are expressed at non-noradrenergic sites in the brain. These non-noradrenergic α2A-ARs play important roles in stress responses, but their cellular mechanisms of action are unclear. In humans, the α2A-AR agonist guanfacine reduces overall craving and uncouples craving from stress, yet minimally affects relapse, potentially due to competing actions in the brain. Here, we show that heteroceptor α2A-ARs postsynaptically enhance dorsal bed nucleus of the stria terminalis (dBNST) neuronal activity in mice of both sexes. This effect is mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels because inhibition of these channels is necessary and sufficient for excitatory actions. Finally, this excitatory action is mimicked by clozapine-N-oxide activation of the Gi-coupled DREADD hM4Di in dBNST neurons and its activation elicits anxiety-like behavior in the elevated plus maze. Together, these data provide a framework for elucidating cell-specific actions of GPCR signaling and provide a potential mechanism whereby competing anxiogenic and anxiolytic actions of guanfacine may affect its clinical utility in the treatment of addiction.SIGNIFICANCE STATEMENT Stress affects the development of neuropsychiatric disorders including anxiety and addiction. Guanfacine is an α2A-adrenergic receptor (α2A-AR) agonist with actions in the bed nucleus of the stria terminalis (BNST) that produces antidepressant actions and uncouples stress from reward-related behaviors. Here, we show that guanfacine increases dorsal BNST neuronal activity through actions at postsynaptic α2A-ARs via a mechanism that involves hyperpolarization-activated cyclic nucleotide gated cation channels. This action is mimicked by activation of the designer receptor hM4Di expressed in the BNST, which also induces anxiety-like behaviors. Together, these data suggest that postsynaptic α2A-ARs in BNST have excitatory actions on BNST neurons and that these actions can be phenocopied by the so-called "inhibitory" DREADDs, suggesting that care must be taken regarding interpretation of data obtained with these tools.