Dopaminergic (DA) neurons are known to play a key role in controlling behaviors. While DA neurons in other brain regions are extensively characterized, those in zona incerta (ZITH or A13) receive much less attention and their function remains to be defined. Here it is shown that optogenetic stimulation of these neurons elicited intensive self-grooming behaviors and promoted place preference, which can be enhanced by training but cannot be converted into contextual memory. Interestingly, the same stimulation increased DA release to periaqueductal grey (PAG) neurons and local PAG antagonism of DA action reduced the elicited self-grooming. In addition, A13 neurons increased their activity in response to various external stimuli and during natural self-grooming episodes. Finally, monosynaptic retrograde tracing showed that the paraventricular hypothalamus represents one of the major upstream brain regions to A13 neurons. Taken together, these results reveal that A13 neurons are one of the brain sites that promote appetitive self-grooming involving DA release to the PAG.

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Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well positioned to impact known DA-related functions as their descending projections innervate target regions that regulate vigilance, sensory integration, and motor execution. Despite this connectivity, little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo, we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects but not reward. A13-DA neurons responded strongly when animals grab and manipulate food items, whereas their inactivation or degeneration prevented animals from successfully doing so-a deficit partially attributed to a reduction in grip strength. By contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Motivation for food was unaffected, as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. An anatomical investigation confirmed that A13-DA neurons project to the superior colliculus (SC) and also demonstrated a novel A13-DA projection to the reticular formation (RF). These results establish a functional role for A13-DA neurons in prehensile actions that are uncoupled from the motivational factors that contribute to the initiation of forelimb movements and help position A13-DA circuits into the functional framework regarding centrally located DA populations and their ability to coordinate movement.

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UNASSIGNED: For hospitalized patients with chronic obstructive pulmonary disease (COPD), albuterol and levalbuterol can both be used as relievers to alleviate bronchoconstriction. This study aimed to evaluate levalbuterol and albuterol\'s cost-utility and budget impact in hospitalized patients with COPD.
UNASSIGNED: A cost-utility analysis was used to evaluate the impact on the costs of nebulized levalbuterol verse albuterol in hospitalized patients with COPD. The decision tree model was employed to estimate the incremental cost per quality-adjusted life year in the admission setting. A budget impact model was used to examine the impact of budget on levalbuterol\'s entry into the Chinese market from the healthcare system\'s perspective. One-way sensitivity and probabilistic sensitivity analyses were performed to test the uncertainty of the parameters.
UNASSIGNED: The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years. The sensitivity analysis indicated that the results were robust to the changes in input parameter values.
UNASSIGNED: Levalbuterol is a cost-saving option for treating hospitalized patients with COPD in China.
Chronic obstructive pulmonary disease (COPD) is a common disease in China, with an increased financial burden over the years. Nebulized albuterol is the most commonly used short-acting beta2-agonist, often regarded as the initial bronchodilator to treat hospitalized COPD patients. Its R-isomer, levalbuterol, entered the Chinese market in 2019. The new intervention always impacts the expenditure of the health system. We built a cost-utility and budget impact model to analyze the difference between albuterol and levalbuterol. The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization compared with albuterol, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years.

OBJECTIVE: Japanese cedar pollinosis (JCP) is a form of seasonal allergic rhinitis that affects 38.8% of the Japanese population. Particularly severe and most severe symptoms among JCP patients can lead to impairments of paid work productivity and unpaid work activities. Indeed, the current standard of care (SoC) is not always able to relieve these symptoms. Omalizumab, a novel JCP treatment recently approved in Japan, provides an effective add-on therapy to the SoC. This study estimates the effect of omalizumab on paid and unpaid work activities (i.e. its social impact) in patients with severe and most severe JCP symptoms in Japan.
METHODS: The impact of omalizumab was estimated through a one-year static cohort model using the Work Productivity and Activity Impairment Allergy Specific (WPAI-AS) questionnaire derived from a clinical trial on omalizumab enrolling patients with severe and most severe JCP symptoms, which had been conducted in Japan. This effect was quantified using Japanese official statistics on employment and time use. The human capital approach and the proxy good approach were employed to monetize paid and unpaid work activities, respectively. A sensitivity analysis was implemented to account for modeling structural uncertainties.
RESULTS: Our results show that the use of omalizumab might reduce the paid and unpaid work productivity losses due to severe and most severe JCP by nearly one-third. In the severe symptom period of three weeks, 36.6 million hours of lost paid and unpaid work hours could be avoided, which sums up to a monetized productivity loss of 728.3 million USD.
CONCLUSIONS: Omalizumab could provide substantial benefits in terms of paid and unpaid work activities in patients with severe and most severe JCP. Our results also highlight the importance of considering unpaid work in estimating productivity costs due to poor health.

BACKGROUND: The aim of this study was to estimate the budget impact of lenalidomide and dexamethasone (RD) versus bortezomib, cyclophosphamide and dexamethasone (VCD) in newly diagnosed multiple myeloma (NDMM) and relapsed refractory (RR) MM patients, from the perspective of the Egyptian Ministry of health (MoH).
METHODS: Two budget impact dynamic models were conducted to assess the budget impact of RD entry over a 3-year period. The clinical data for the modeled cohorts were based on published articles. Total annual medical costs associated with non-progression and progression disease states included the sum of estimated costs for adverse effects management, concomitant treatments, hospitalization and the follow up were measured. Deterministic sensitivity analyses were performed.
RESULTS: The target population in a given year was estimated to include 245 patients with RRMM and 291 patients with NDMM receiving RD versus VCD. In RRMM, the annual budget savings of lenalidomide entry were estimated at EGP -1,103,969, -3,362,793 and -5,949,228 at year 1, year 2 and year 3, respectively. In NDMM, the annual budget savings of lenalidomide entry were estimated at EGP869,415, -1,779,776 and -2,139,311 at year 1, year 2 and year 3, respectively, to the payer after lenalidomide entry. The model results in RRMM were most sensitive to variations in patients eligible to transplantation in RRMM. In NDMM, the model results were most sensitive to the market share of VCD in the first year.
CONCLUSIONS: The results of our BI models suggest that not only does RD treatment have an effect on the budget, but also has major cost savings in other areas which are very important while considering the total costs of MM treatment. This study results provided evidence-based information to the MoH that will help in decision making of whether to implement RD as a treatment intervention or not.

Objective: To estimate the economic burden of needlestick injuries (NSIs) among healthcare workers (HCWs) in China.Design: A model was built to evaluate the economic burden of NSIs.Methods: The cost model was developed from a societal perspective, including both direct and indirect costs, with lifetime horizon. The direct costs were categorized into infection prevention and treatment of infections. The indirect cost included productivity loss of both HCWs and his/her family members due to the blood-borne infections. Sub-group analyses were conducted to estimate the cost per NSI when the source patient (SP) was confirmed with hepatitis B virus/hepatitis C virus/human immunodeficiency virus (HBV/HCV/HIV) infection. One-way and probabilistic sensitivity analyses were conducted for all parameters to examine the robustness of the result.Results: The model projected a total cost of ¥699 for each NSI (direct and indirect cost were ¥553 and ¥146, respectively). The cost per NSI when the SP was confirmed with HBV/HCV/HIV was ¥4,238, ¥18,404, and ¥6,152, respectively. The total economic burden of NSIs among HCWs in China was estimated to be ¥5.8 billion, and about half of the cost was associated with NSIs in nurses, at ¥2.8 billion.Limitations: This study did not incorporate the costs of litigation/psychological, and the prevalence of the infections was based on the general population, so the actual costs per NSI may be underestimated. More real-world studies of treatment cost about HBV/HCV are needed to further supporting this study.Conclusions: The economic burden of NSIs among HCWs in China is substantial. Comprehensive NSI prevention programs, including implementation of safety needles and devices, have high potential for healthcare institutions to achieve downstream cost savings and cost offsets.