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Ataru Igarashi,1 Manabu Akazawa,2 Tatsunori Murata,3 Toshihiko Taguchi,4 Alesia Sadosky,5 Nozomi Ebata,6 Richard Willke,5 Koichi Fujii,6 Jim Doherty,5 Makoto Kobayashi3 1Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 2Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan; 3CRECON Medical Assessment Inc., Tokyo, Japan; 4Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 5Pfizer Inc., New York, NY, USA; 6Pfizer Japan, Inc., Tokyo, Japan Objective: To assess the cost-effectiveness of pregabalin for the treatment of chronic low back pain with accompanying neuropathic pain (CLBP-NeP) from the health care payer and societal perspectives. Methods: The cost-effectiveness of pregabalin versus usual care for treatment of CLBP-NeP was evaluated over a 12-month time horizon using the incremental cost-effectiveness ratio (ICER). Quality-adjusted life years (QALYs), derived from the five-dimension, five-level EuroQol (EQ-5D-5L) questionnaire, was the measure of effectiveness. Medical costs and productivity losses were both calculated. Expected costs and outcomes were estimated via cohort simulation using a state-transition model, which mimics pain state transitions among mild, moderate, and severe pain. Distributions of pain severity were obtained from an 8-week noninterventional study. Health care resource consumption for estimation of direct medical costs for pain severity levels was derived from a physician survey. The ICER per additional QALY gained was calculated and sensitivity analyses were performed to evaluate the robustness of the assumptions across a range of values. Results: Direct medical costs and hospitalization costs were both lower in the pregabalin arm compared with usual care. The estimated ICERs in the base case scenarios were approximately ¥2,025,000 and ¥1,435,000 per QALY gained with pregabalin from the payer and societal perspectives, respectively; the latter included indirect costs related to lost productivity. Sensitivity analyses using alternate values for postsurgical pain scores (0 and 5), initial pain severity levels (either all moderate or all severe), and the actual EQ-5D-5L scores from the noninterventional study showed robustness of results, with ICERs that were similar to the base case. Development of a cost-effectiveness acceptability curve showed high probability (≥75%) of pregabalin being cost-effective. Conclusion: Using data and assumptions from routine clinical practice, pregabalin is cost-effective for the treatment of CLBP-NeP in Japan. Keywords: usual care, neuropathic pain, Markov model, quality-adjusted life-year, willingness to pay, health economics

The potential of antiferroelectrics to exhibit a negative capacitance regime has been largely overlooked as all the attention focused on their polar counterparts, ferroelectrics. We use nonequilibrium first-principles-based molecular dynamics to probe a negative capacitance regime in prototypical antiferroelectric PbZrO 3. Simulations predict that this antiferroelectric can exhibit a negative capacitance/susceptibility regime in response of polarization to an internal electric field, which is a superposition of applied and residual depolarizing fields. Consequently, the regime emerges when the polarization surface charge in the polar phase of antiferroelectric is not fully screened, as is often the case in thin films and nanostructures. The negative capacitance regime occurs below the Curie temperature and disappears in the paraelectric phase. We find that the time the material spends in the negative capacitance regime is proportional to the time needed to complete antipolar–polar (or its reverse) transition and shortens as the frequency of the applied field increases. Moreover, a negative susceptibility value exhibits strong dependence on the quality of surface charge screening with the largest in magnitude values occurring in the vicinity of the transition into a negative capacitance regime. [ABSTRACT FROM AUTHOR]

The potential of antiferroelectrics to exhibit a negative capacitance regime has been largely overlooked as all the attention focused on their polar counterparts, ferroelectrics. We use nonequilibrium first-principles-based molecular dynamics to probe a negative capacitance regime in prototypical antiferroelectric PbZrO 3. Simulations predict that this antiferroelectric can exhibit a negative capacitance/susceptibility regime in response of polarization to an internal electric field, which is a superposition of applied and residual depolarizing fields. Consequently, the regime emerges when the polarization surface charge in the polar phase of antiferroelectric is not fully screened, as is often the case in thin films and nanostructures. The negative capacitance regime occurs below the Curie temperature and disappears in the paraelectric phase. We find that the time the material spends in the negative capacitance regime is proportional to the time needed to complete antipolar–polar (or its reverse) transition and shortens as the frequency of the applied field increases. Moreover, a negative susceptibility value exhibits strong dependence on the quality of surface charge screening with the largest in magnitude values occurring in the vicinity of the transition into a negative capacitance regime. [ABSTRACT FROM AUTHOR]