Brightening deep-blue perovskite light-emitting diodes: A path to Rec. 2020.

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients. Objectives: This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration. Design: This is a systematic review and meta-analysis. Data sources and methods: A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores. Results: Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively. Conclusion: Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.

Use of gastrointestinal prokinetics and the risk of parkinsonism: A population-based case-crossover study.

BACKGROUND: The disease burden of parkinsonism is extremely costly in the United States. Unlike Parkinson's disease, drug-induced parkinsonism (DIP) is acute and reversible; exploring the causative drug is important to prevent DIP in patients at high-risk of parkinsonism. OBJECTIVE: To examine whether the use of gastrointestinal (GI) prokinetics is associated with an increased risk of parkinsonism. METHODS: We conducted a case-crossover study using nationally representative data. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) between January 1, 2007 and December 1, 2015. The first prescription date of G20, G21.1, or G25.1 diagnoses was defined as the index date (0 day). Patients with prior extrapyramidal and movement disorders or brain tumors were excluded. We assessed the exposure within the risk (0-29 days) and control periods (60-89 days), before or on the index date. Conditional logistic regression estimated the adjusted odds ratio (aOR) for parkinsonism. RESULTS: Overall, 2268 and 1674 patients were exposed to GI prokinetics during the risk and control periods, respectively. The use of GI prokinetics significantly increased the occurrence of parkinsonism (aOR = 2.31; 95% Confidence Interval [CI], 2.06-2.59). The use of GI prokinetics was associated with a higher occurrence of parkinsonism in elderly patients (≥65 years old; aOR = 2.69; 95% CI, 2.30-3.14) than in younger patients (aOR = 1.90; 95% CI, 1.59-2.27). CONCLUSIONS: The use of GI prokinetics was significantly associated with higher occurrences of parkinsonism, necessitating close consideration when using GI prokinetics.

Treatment Changes and Prognoses in Patients with Incident Drug-Induced Parkinsonism Using a Korean Nationwide Healthcare Claims Database.

This retrospective cohort study assessed treatment changes and prognoses after incident drug-induced parkinsonism (DIP). We used the National Health Insurance Service's National Sample Cohort database in South Korea. We selected patients diagnosed with incident DIP and given prescriptions to take offending drugs (antipsychotics, gastrointestinal (GI) motility drugs, or flunarizine) for a period of time that overlapped with the time of DIP diagnosis during 2004-2013. The proportion of patients experiencing each type of treatment change and prognosis was assessed for 2 years after DIP diagnosis. We identified 272 patients with incident DIP (51.9% of patients were aged ≥ 60 years and 62.5% of them were women). Switching (38.4%) and reinitiation (28.8%) were the most common modifications in GI motility drug users, whereas dose adjustment (39.8%) and switching (23.0%) were common in antipsychotic users. The proportion of persistent users was higher among antipsychotic users (7.1%) than that among GI motility drug users (2.1%). Regarding prognosis, 26.9% of patients experienced DIP recurrence or persistence, the rate being the highest in persistent users and the lowest in patients who discontinued the drug. Among patients with incident DIP diagnoses, the patterns of treatment change and prognosis differed across the types of offending drugs. Over 25% of patients experienced DIP recurrence or persistence, highlighting the need for an effective strategy to prevent DIP.

The Photoactive Photosynthetic Reaction Center of a Rhodobacter sphaeroides Mutant Lacking 3-Vinyl (Bacterio)Chlorophyllide a Hydratase Contains 3-Vinyl Bacteriochlorophyll a.

Rhodobacter sphaeroides mutant BF-lacking 3-vinyl (bacterio)chlorophyllide a hydratase (BchF)-accumulates chlorophyllide a (Chlide a) and 3-vinyl bacteriochlorophyllide a (3V-Bchlide a). BF synthesizes 3-vinyl bacteriochlorophyll a (3V-Bchl a) through prenylation of 3V-Bchlide a and assembles a novel reaction center (V-RC) using 3V-Bchl a and Mg-free 3-vinyl bacteriopheophytin a (3V-Bpheo a) at a molar ratio of 2:1. We aimed to verify whether a bchF-deleted R. sphaeroides mutant produces a photochemically active RC that facilitates photoheterotrophic growth. The mutant grew photoheterotrophically-implying a functional V-RC-as confirmed by the emergence of growth-competent suppressors of bchC-deleted mutant (BC) under irradiation. Suppressor mutations in BC were localized to bchF, which diminished BchF activity and caused 3V-Bchlide a accumulation. bchF expression carrying the suppressor mutations in trans resulted in the coproduction of V-RC and wild-type RC (WT-RC) in BF. The V-RC had a time constant (τ) for electron transfer from the primary electron donor P (a dimer of 3V-Bchl a) to the A-side containing 3V-Bpheo a (HA) similar to that of the WT-RC and a 60% higher τ for electron transfer from HA to quinone A (QA). Thus, the electron transfer from HA to QA in the V-RC should be slower than that in the WT-RC. Furthermore, the midpoint redox potential of P/P+ of the V-RC was 33 mV more positive than that of the WT-RC. R. sphaeroides, thus, synthesizes the V-RC when 3V-Bchlide a accumulates. The V-RC can support photoheterotrophic growth; however, its photochemical activity is inferior to that of the WT-RC. IMPORTANCE 3V-Bchlide a is an intermediate in the bacteriochlorophyll a (Bchl a)-specific biosynthetic branch and prenylated by bacteriochlorophyll synthase. R. sphaeroides synthesizes V-RC that absorbs light at short wavelengths. The V-RC was not previously discovered because 3V-Bchlide a does not accumulate during the growth of WT cells synthesizing Bchl a. The levels of reactive oxygen species increased with the onset of photoheterotrophic growth in BF, resulting in a long lag period. Although the inhibitor of BchF is unknown, the V-RC may act as a substitute for the WT-RC when BchF is completely inhibited. Alternatively, it may act synergistically with WT-RC at low levels of BchF activity. The V-RC may broaden the absorption spectra of R. sphaeroides and supplement its photosynthetic ability at various wavelengths of visible light to a greater extent than that by the WT-RC alone.

A population-based study on the risk of prescription opioid abuse in patients with chronic opioid use and cost-effectiveness of prescription drug monitoring program using a patient simulation model in South Korea.

BACKGROUND: Concerns regarding the burden of inappropriate opioid use are growing. We examined the association between prescription opioid abuse and patient characteristics and estimated the cost-effectiveness of the prescription drug monitoring program (PDMP) implemented in South Korea, considering patient-level information. METHODS: A retrospective cohort study was conducted to explore the association between opioid abuse and patient characteristics using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. We selected non-cancer patients with chronic opioid use and investigated the incidence of opioid abuse between 2010 and 2015. The association between opioid abuse and patient characteristics was assessed using the Cox proportional hazards model. The cost-effectiveness of the PDMP was assessed using discrete event simulation (DES) with a time horizon of 30 years from a societal perspective. Time-to-event data and event costs were obtained from the NHIS-NSC database. The abuse rate was adjusted for each patient based on the baseline characteristics and history of abuse experienced in the model. Program effectiveness, program costs, and health-state utilities were obtained from the published literature. The incremental cost-utility ratio (ICUR) was estimated at a discount rate of 5% for both costs and quality-adjusted life-years (QALYs). RESULTS: We identified 22,524 patients with chronic opioid use in the NHIS-NSC database. Every one-year increase in age (hazard ratio: 1.002 [95% CI: 1.000-1.003]), medical aid program (1.130 [95% CI: 1.072-1.191]), high Charlson Comorbidity Index (1.054 [95% CI: 1.044-1.065]), and history of opioid abuse (1.501 [95% CI: 1.391-1.620] and 3.005 [95% CI: 2.387-3.783] for 1-2 and ≥3 abuse events, respectively) significantly increased the risk of opioid abuse. In the DES, the PDMP was cost-effective, with an estimated ICUR of $2,227/QALY, which was most affected by the program's effectiveness. CONCLUSION: Patient characteristics and history of opioid abuse affected the risk of opioid abuse. Considering patient-level information, the PDMP implemented in South Korea is likely to be cost-effective.

Singlet fission dynamics modulated by molecular configuration in covalently linked pyrene dimers, Anti- and Syn-1,2-di(pyrenyl)benzene.

Covalently linked dimers (CLDs) and their structural isomers have attracted much attention as potential materials for improving power conversion efficiencies through singlet fission (SF). Here, we designed and synthesized two covalently ortho-linked pyrene (Py) dimers, anti- and syn-1,2-di(pyrenyl)benzene (Anti-DPyB and Syn-DPyB, respectively), and investigated the effect of molecular configuration on SF dynamics using steady-state and time-resolved spectroscopies. Both Anti-DPyB and Syn-DPyB, which have different Py-stacking configurations, form excimers, which then relax to the correlated triplet pair ((T1T1)) state, indicating the occurrence of SF. Unlike previous studies where the excimer formation inhibited an SF process, the (T1T1)'s of Anti-DPyB and Syn-DPyB are formed through the excimer state. The dissociation of (T1T1)'s to 2T1 in Anti-DPyB is more favorable than in Syn-DPyB. Our results showcase that the molecular configuration of a CLD plays an important role in SF dynamics.

Exploring the prevalence and characteristics of adverse drug events among older adults in South Korea using a national health insurance database.

Background: Adverse drug events (ADEs) in the elderly frequently occur because of their multiple chronic diseases and complexity of drug therapy. To better understand adverse drug events, the prevalence and characteristics of adverse drug events in elderly South Korean patients were assessed. Methods: The National Health Insurance databases for 2015 and 2016 were used for the analysis. We included patients aged ≥65 years that had at least one claim with the diagnosis codes 'drug-induced,' 'poisoning by drug,' and 'vaccine-associated' each year for the base-case analysis. To minimize the underestimation of adverse drug event prevalence, we also used an extended definition analysis by adding the 'adverse drug event very likely' codes. We estimated the prevalence of adverse drug events by sex, age group, and type of insurance and examined the frequent types of adverse drug events in 2015 and 2016. Results: In the base-case analysis, adverse drug event prevalence in individuals aged 65 years and older was 2.75% in 2015 and 2.77% in 2016. With advanced age, the prevalence of adverse drug event tended to increase, peaking in the age group of 75-79 years. In addition, the adverse drug event prevalence was higher in females and Medical Aid enrollees. The most frequently occurring adverse drug event was 'allergy, unspecified,' followed by 'other drug-induced secondary parkinsonism,' and 'generalized skin eruption due to drugs and medicaments.' When we examined the extended definition analysis, the prevalence of adverse drug events was 4.47% in 2015 and 4.52% in 2016, which significantly increased from those estimated in the base-case analysis. Conclusion: Among the older adults, the prevalence of adverse drug event was higher in advanced age, females, and Medical Aid enrollees. In particular, allergy and drug-induced secondary parkinsonism frequently occurred. This study provides evidence that health policies addressing the prevention and management of adverse drug events should be a priority for the most vulnerable elderly patients.

Economic burden of opioid misuse focused on direct medical costs.

Background: Since their development, synthetic opioids have been used to control pain. With increased opioid use, problematic opioid prescription has also increased, resulting in a growing economic burden. However, there is a paucity of research studies on the economic burden of prescription opioid misuse in Asia, especially South Korea. Objectives: To estimate the incremental economic burden of prescription opioid misuse for the South Korean population. Methods: The National Health Insurance Service-National Sample Cohort database, covering 2% of the South Korean population between 2010 and 2015, was analyzed. Outpatients aged 18 or older who took one or more prescription opioids were selected. Based on their opioid prescription patterns, patients were classified into opioid misuse and non-misuse groups. The direct medical costs per person per year (PPPY) and the incremental economic burden of the opioid misuse group were explored using an exponential conditional model with a suitable distribution and log link function. All analyses were performed using SAS® Enterprise Guide version 9.4, and p < 0.05 was considered statistically significant. Results: The number of patients who had ≥1 opioid prescription was 345,020 including 84,648 (24.53%) in the opioid misuse group and 260,372 (75.47%) in the non-misuse group. The adjusted mean direct medical costs PPPY were estimated to be USD 401 for the opioid misuse group, which is 1.49 times significantly higher than that for the non-misuse group (p < 0.0001). The incremental economic burden of the opioid misuse group in the South Korean population was estimated to be approximately USD 0.52 billion for the period 2010-2015. Conclusion: Prescription opioid misuse was significantly associated with the increased economic burden. Along with proper policies for using opioids, it is necessary to monitor opioid prescription patterns to prevent opioid misuse and reduce the related economic burden.

Evaluation of Factors Associated with Adverse Drug Events in South Korea Using a Population-Based Database.

This retrospective study aims to investigate the factors associated with the occurrence of ADEs using nationally representative claims data. All patients with at least one claim with diagnosis codes denoting potential ADE between 1 July 2015 and 31 December 2015 were included. Potential ADE was defined as ADE identified in the claims data, because it was not verified. The index date was defined as the date of the first claim with potential ADEs. Demographic data were collected at the index date, while data on comorbidities and number of medications used were collected six months before the index date. Multivariate logistic regression was used to explore the association between potential ADEs and several factors, including sex, age group, insurance type, comorbidities, and number of prescribed medications. Patients with potential ADEs were older, had more chronic diseases, and used more medications than those without potential ADEs. In the multivariate analysis, occurrence of potential ADEs was associated with age (≥65 years, odds ratio [OR] 1.15, 95% confidence interval [CI] 1.08-1.21), Medical Aid program (OR 1.37, 95% CI 1.27-1.47), Charlson Comorbidity Index scores (≥5, OR 2.87, 95% CI 2.56-3.20), and use of six or more medications (6-10 medications, OR 1.89, 95% CI 1.79-1.99). Age, Medical Aid program, comorbidities, and number of medications were associated with occurrence of potential ADEs.

Clinical and economic impact of changing reimbursement criteria for statin treatment among patients with type 2 diabetes mellitus in South Korea.

Aim: Patients with type 2 diabetes mellitus (T2DM) in South Korea can be reimbursed for statins if they have a low-density lipoprotein cholesterol (LDL-C) level of ≥100 mg/dL. We aimed to explore the clinical and economic benefit received by T2DM patients when easing the current criteria for statin treatment by lowering the LDL-C threshold from 100 mg/dL to 70 mg/dL. Methods: We used a static course model with a 5-year period to compare the following two scenarios in T2DM patients with no history of cardiovascular (CV) events: the current criteria covering LDL-C ≥100 mg/dL and the revised criteria covering LDL-C ≥70 mg/dL. The number of target patients was estimated based on previous Korean studies on patients with T2DM. The current mix of treatments used for T2DM and costs involving CV events were estimated using the National Health Insurance Service-National Health Screening Cohort database. The baseline CV event rates and case fatality were estimated using NHIS Customized database, including 50% patients who were prescribed atorvastatin and 100% who were not prescribed statins between 2009 and 2012 among patients with T2DM in the entire Korean population. After propensity score matching, patients with T2DM not prescribed statins were followed up until 2018 to estimate the incidence rates of coronary heart disease (CHD) and stroke. The efficacy of atorvastatin for the primary prevention of CV events in patients with T2DM was derived from a pivotal clinical trial. The outcome measures were the number of CV events prevented after the change in criteria and the consequent cost savings. Results: In South Korea, the current and revised criteria covered 2,434,379 and 3,446,149 patients with T2DM, respectively. The change in criteria resulted in the prevention of 726 CV events and cost savings of US dollars (USD) 5.5 million at the national level and USD 0.0089 per member per month in the fifth year. Conclusion: Easing the reimbursement criteria for statin treatment among patients with T2DM was associated with a reduction in CV events and their related costs; therefore, changing the reimbursement criteria is worth further consideration to mitigate the burden of CV disease.

Solvent-modulated proton-coupled electron transfer in an iridium complex with an ESIPT ligand.

Proton-coupled electron transfer (PCET), an essential process in nature with a well-known example of photosynthesis, has recently been employed in metal complexes to improve the energy conversion efficiency; however, a profound understanding of the mechanism of PCET in metal complexes is still lacking. In this study, we synthesized cyclometalated Ir complexes strategically designed to exploit the excited-state intramolecular proton transfer (ESIPT) of the ancillary ligand and studied their photoinduced PCET in both aprotic and protic solvent environments using femtosecond transient absorption spectroscopy and density functional theory (DFT) and time-dependent DFT calculations. The data reveal solvent-modulated PCET, where charge transfer follows proton transfer in an aprotic solvent and the temporal order of charge transfer and proton transfer is reversed in a protic solvent. In the former case, ESIPT from the enol form to the keto form, which precedes the charge transfer from Ir to the ESIPT ligand, improves the efficiency of metal-to-ligand charge transfer. This finding demonstrates the potential to control the PCET reaction in the desired direction and the efficiency of charge transfer by simply perturbing the external hydrogen-bonding network with the solvent.

Comorbidities and Antithrombotic Treatment Pattern in Patients With Atrial Fibrillation.

Objective: Non-vitamin K antagonist oral anticoagulants (NOACs) are proven alternatives to warfarin for preventing stroke in patients with non-valvular atrial fibrillation. We aimed to examine the treatment patterns and patient factors associated with the use of antiplatelet agents, warfarin, and NOACs in clinical practice. Methods: We conducted a retrospective cohort study using the Korean Health Insurance Review & Assessment Service database. Patients receiving antithrombotics were identified before and after the introduction of NOACs (from August 1, 2013 to December 30, 2014 and July 1, 2015 to November 30, 2016, respectively). Patients were included if they were aged ≥18 years, had an atrial fibrillation diagnosis, and had a CHA2DS2-VASc score ≥2. Treatment pattern was assessed by classifying patients into NOAC, warfarin, or antiplatelet users based on the first date of antithrombotic prescription. Clinical factors associated with the type of antithrombotics chosen were examined using logistic regression analyses. Results: We identified 129,465 and 196,243 patients before and after the introduction of NOACs, respectively. The proportion of antiplatelet users was 60.7 and 53.0% before and after the introduction of NOACs, respectively. The proportion of warfarin users was higher in patients with low HAS-BLED score, high CHA2DS2-VASc score, or stroke before the NOAC era. A similar trend was observed for NOAC and warfarin users after the introduction of NOAC. Compared with antiplatelets, warfarin and NOAC uses were significantly associated with CHA2DS2-VASc score and stroke, whereas presence of myocardial infarction (MI) and peripheral arterial disease were significantly associated with antiplatelets prescription. For comparisons between NOAC and warfarin, HAS-BLED and CHA2DS2-VASc scores showed significant associations with NOAC use, whereas comorbidities including MI were significantly associated with warfarin use. Conclusions: The treatment pattern of antithrombotics did not change with the introduction of NOACs. However, comorbidities served as an important factor in choosing treatment regardless of NOAC entry.

Priorities in the Prevention Strategies for Medication Error Using the Analytical Hierarchy Process Method.

As medication error is inherently "preventable", we should try to minimize errors to improve patient safety and quality of care. The aim of this study was to prioritize strategies to prevent medication errors using the analytic hierarchy process (AHP) method. The hierarchy structure consisted of three stages: goal of the decision, decision criteria, and alternatives. Ten experts of patient safety research or clinical pharmacology compared each pair of criteria and alternatives and assigned a nine-point numerical scale. We used the eigenvector method to aggregate the pairwise comparisons obtained from experts and to estimate the weights of each criterion and alternative. Among the decision criteria, system improvement in reporting was the most preferred criterion, followed by cultural improvement and system improvement in the counterplan. The preferred alternative was a counterplan by healthcare institutions, followed by a change from a blame culture to safety culture and the building of a reporting system. A sensitivity analysis indicated that priorities were generally robust in the methods used for calculating the integrated matrices. We have suggested the priority of preventive strategies against medication errors using the AHP method. The prioritization of preventive strategies could help policymakers understand current needs and therefore develop evidence-based policies on patient safety.

Cost-Effectiveness and Value of Information of Cabozantinib Treatment for Patients with Advanced Renal Cell Carcinoma After Failure of Prior Therapy in South Korea.

OBJECTIVE: To estimate the cost-effectiveness and value of information of cabozantinib compared to nivolumab in advanced renal cell carcinoma (RCC) patients, who previously failed treatment from a societal perspective in South Korea. METHODS: A partitioned survival model was used to evaluate the incremental cost-utility ratio (ICUR) of cabozantinib versus nivolumab. Overall survival (OS) and progression-free survival (PFS) curves were obtained from a network meta-analysis that included METEOR and CheckMate 025 trial results. Utility values for health states and adverse events were estimated based on the EQ-5D-5L data of METEOR trial with a Korean-specific tariff. Costs were estimated by a micro-costing approach using healthcare claims data and expert consultation. The impact of uncertainties in the model were explored by scenario analyses, and deterministic and probabilistic sensitivity analyses. The expected value of perfect information (EVPI) was estimated to assess the value of future research to decrease decision uncertainty. RESULTS: Compared to nivolumab, cabozantinib was associated with improved OS, PFS, and quality-adjusted life-years (QALYs) at greater cost. The ICUR was $34,445 per QALY. In sensitivity analysis, drug costs had the greatest influence on the ICUR. Cabozantinib had a 68.0% probability of being cost-effective at a threshold of 2 times gross domestic product (GDP) per capita. The population EVPI was $82.6 million at 2 GDP threshold. CONCLUSIONS: Cabozantinib was found to be cost-effective for advanced RCC patients after failure of prior therapy at a 2 GDP threshold. Future research that costs less than the estimated population EVPI would be worth considering for a comparison of cabozantinib and nivolumab.

Cost-Effectiveness of an Opioid Abuse-Prevention Program Using the Narcotics Information Management System in South Korea.

OBJECTIVES: To assess the cost-effectiveness of an opioid abuse-prevention program embedded in the Narcotics Information Management System ("the Network System to Prevent Doctor-Shopping for Narcotics") in South Korea. METHODS: Using a Markov model with a 1-year cycle length and 30-year time horizon, we estimated the incremental cost-utility ratio (ICUR) of implementing an opioid abuse-prevention program in patients prescribed outpatient opioids from a Korean healthcare payer's perspective. The model has 6 health states: no opioid use, therapeutic opioid use, opioid abuse, overdose, overdose death, and all-cause death. Patient characteristics, healthcare costs, and transition probabilities were estimated from national population-based data and published literature. Age- and sex-specific utilities of the general Korean population were used for the no-use state, whereas the other health-state utilities were obtained from published studies. Costs (in 2019 US dollars) included the expenses of the program, opioids, and overdoses. An annual 5% discount rate was applied to the costs and quality-adjusted life-years (QALYs). Parameter uncertainties were explored via deterministic and probabilistic sensitivity analyses. RESULTS: The program was associated with 2.27 fewer overdoses per 100 000 person-years, with an ICUR of $227/QALY. The ICURs were generally robust to parameter changes, although the program's effect on abuse reduction was the most influential parameter. Probabilistic sensitivity analysis showed that the program reached a 100% probability of cost-effectiveness at a willingness-to-pay threshold of $900/QALY. CONCLUSIONS: The opioid abuse-prevention program appears to be cost-effective in South Korea. Mandatory use of the program should be considered to maximize clinical and economic benefits of the program.

Charge transfer induced by electronic state mixing in a symmetric X-Y-X-type multi-chromophore system.

Charge transfer (CT) from electron donor (D) to acceptor (A) plays an important role in photoelectric or electrochemical devices and is a useful concept for a molecule with D and A well distinguishable. Here, we report our finding that even in a molecule with D and A not resolvable, CT can be induced by electronic state mixing (ESM) in a symmetric multi-chromophore system (MCS), namely 1,4-di(1-pyrenyl)benzene (Py-Benz-Py). Unlike Py and Py-Benz, Py-Benz-Py exhibits unique photophysical properties attributable to the reduction of the energy gap between two electronic states induced by ESM. The ESM for Py-Benz-Py is due to the extended π-conjugation owing to the further introduction of Py into Py-Benz, and consequently leads to the favorable intramolecular CT, followed by the planarization due to the twisting motion between Py and phenyl moieties. Time-resolved spectroscopic data demonstrate that the twisting process of the Py moiety in acetonitrile occurs with two unequal time constants, suggesting the localized CT state and the asynchronous twisting dynamics of two Py moieties unlike the delocalized CT state in nonpolar and low-polarity solvents leading to the synchronous twisting of two Py moieties. This means that the symmetry-breaking CT in MCSs can induce an asynchronous twisting motion. The results reported here support that a molecule without CT can be turned into another molecule with CT induced by ESM and demonstrate that the excited-state relaxation dynamics can be regulated through the ESM induced by introducing the substituents or changing the environmental factors such as solvent polarities.

Gold Nanoparticle Formation via X-ray Radiolysis Investigated with Time-Resolved X-ray Liquidography.

We report the generation of gold nanoparticles (AuNPs) from the aqueous solution of chloro(2,2',2″-terpyridine)gold(III) ion ([Au(tpy)Cl]2+) through X-ray radiolysis and optical excitation at a synchrotron. The original purpose of the experiment was to investigate the photoinduced structural changes of [Au(tpy)Cl]2+ upon 400 nm excitation using time-resolved X-ray liquidography (TRXL). Initially, the TRXL data did not show any signal that would suggest structural changes of the solute molecule, but after an induction time, the TRXL data started to show sharp peaks and valleys. In the early phase, AuNPs with two types of morphology, dendrites, and spheres, were formed by the reducing action of hydrated electrons generated by the X-ray radiolysis of water, thereby allowing the detection of TRXL data due to the laser-induced lattice expansion and relaxation of AuNPs. Along with the lattice expansion, the dendritic and spherical AuNPs were transformed into smaller, raspberry-shaped AuNPs of a relatively uniform size via ablation by the optical femtosecond laser pulse used for the TRXL experiment. Density functional theory calculations confirm that the reduction potential of the metal complex relative to the hydration potential of X-ray-generated electrons determines the facile AuNP formation observed for [Au(tpy)Cl]2+.

Cultural Adaptation and Validation of the Korean Version of the iMTA Productivity Cost Questionnaire.

This study develops the Korean version of the Institute for Medical Technology Assessment Productivity Cost Questionnaire (iPCQ) through translation/cultural adaptation and evaluation of psychometric properties. We included 110 outpatients visiting a gynecology clinic. We conducted the translation and cross-cultural adaptation of the iPCQ, including forward and back-translation, pilot test with cognitive debriefing, and finalization. We analyzed the feasibility (using average time of filling in the iPCQ and the proportion of missing values), test-retest reliability (using the intra-class correlation coefficient [ICC]), and validity (concurrent validity with the Work Productivity and Activity Impairment [WPAI] and construct validity with the 36-Item Short Form Survey [SF-36], using Spearman's ρ). The Korean version of iPCQ showed appropriate feasibility (average filling in time was 5.0 min without missing values), and had excellent values in the domains of absenteeism, presenteeism, and unpaid work for test-retest reliability (ICC: 0.92-0.99). For concurrent validity, the Korean version of iPCQ showed moderate-high correlation for absenteeism and presenteeism with the WPAI. All domains of productivity losses measured by the Korean version of iPCQ showed negative correlation with the quality of life estimated by the SF-36. Through this study, we developed a Korean instrument that can measure and value health-related productivity losses including unpaid work as well as absenteeism and presenteeism.

Efficacy and safety of herbal medicine (Dangguijagyag-san) for primary dysmenorrhea: study protocol for a randomized, double-blind, placebo-controlled, parallel-group, multi-center trial.

BACKGROUND: Dangguijagyag-san, also known as Dangguishaoyao-san in Chinese and Toki-shakuyakui-san in Japanese, has been frequently used to treat symptoms associated with dysmenorrhea. The purpose of this trial is to evaluate the efficacy and safety of the herbal medicine, Dangguijagyag-san, relative to those of active control, Gamisoyo-san, and a placebo control for primary dysmenorrhea. METHODS: This protocol details a randomized, double-blind, parallel-group, multi-center, investigator-initiated, controlled trial evaluating treatment of primary dysmenorrhea. Two hundred and forty participants will be randomly divided into one of three groups: 1) the Dangguijagyag-san experimental group (EG) (n = 105), 2) the Gamisoyo-san active control group (ACG) (n = 30), and 3) the placebo control group (PCG) (n = 105). The interventions will be administered for two menstrual cycles, and the follow-up will be carried out for the following six menstrual cycles. The primary outcomes are difference in response rates between the EG and the ACG (non-inferiority comparison) and difference in changes from baseline in average pain intensity measured by the visual analogue scale between the EG and PCG (superiority comparison). The secondary outcomes are pain scores derived from pain assessment tools (verbal multidimensional scoring system, retrospective symptom scale, and short form McGill pain questionnaire), dosage of analgesics, pattern diagnosis questionnaires, and short form 36 health survey. Adverse events and vital signs will be checked at every visit, and laboratory tests will be performed for safety evaluation. DISCUSSION: The results of this clinical trial will offer evidence for the efficacy and safety of Dangguijagyag-san for primary dysmenorrhea. TRIAL REGISTRATION: Clinical Research Information Service of Korea: KCT0003005.