Sequential Effect of Dual-Layered Hybrid Graphite Anodes on Electrode Utilization During Fast-Charging Li-Ion Batteries.

To recharge lithium-ion batteries quickly and safely while avoiding capacity loss and safety risks, a novel electrode design that minimizes cell polarization at a higher current is highly desired. This work presents a dual-layer electrode (DLE) technology via sequential coating of two different anode materials to minimize the overall electrode resistance upon fast charging. Electrochemical impedance spectroscopy and distribution of relaxation times analysis revealed the dynamic evolution of electrode impedances in synthetic graphite (SG) upon a change in the state of charge (SOC), whereas the natural graphite (NG) maintains its original impedance regardless of SOC variation. This disparity dictates the sequence of the NG and SG coating layers within the DLE, considering the temporal SOC gradient developed upon fast charging. Simulation and experimental results suggest that DLE positioning NG and SG on the top (second-layer) and bottom (first-layer), respectively, can effectively reduce the overall resistance at a 4 C-rate (15-min charging), demonstrating two times higher capacity retention (61.0%) over 200 cycles than its counterpart with reversal sequential coating, and is higher than single-layer electrodes using NG or NG/SG binary mixtures. Hence, this study can guide the combinatorial sequence for multi-layer coating of various active materials for a lower-resistivity, thick-electrode design.

Investigation of hepatic adverse events due to quetiapine by using the common data model.

PURPOSE: Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM). METHODS: This was a retrospective observational study involving a nested case-control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment. RESULTS: The numbers of patients with non-serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03-2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16-2.66). CONCLUSION: Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage.

HLA-A*24:02 increase the risk of allopurinol-induced drug reaction with eosinophilia and systemic symptoms in HLA-B*58:01 carriers in a Korean population; a multicenter cross-sectional case-control study.

Background: HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01. Methods: Subjects with B*58:01 were enrolled (21 allopurinol-induced DRESS and 52 allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson's chi-square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development. Results: Frequencies of A*24:02 (71.4 vs. 17.3%, p < 0.001, odds ratio [OR] = 12.0; 95% confidence interval [CI], 3.6-39.2) were significantly higher in B*58:01 (+) DRESS than B*58:01 (+) tolerant controls. In addition, DRB1*13:02 further increased the risk of DRESS. The phenotype frequency of A*24:02/DRB1*13:02 was significantly higher in the B*58:01 (+) DRESS group than in the B*58:01 (+) tolerant controls (52.4% vs. 5.8%, p < 0.001, OR, 66.0; 95% CI, 6.1-716.2). In 2782 allopurinol user cohort, the overall prevalence of DRESS was 0.22%, which increased to 1.62% and 2.86% in the presence of B*58:01 and B*58:01/A*24:02, respectively. Conclusion: The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.

Risk factors of beta-lactam anaphylaxis in Korea: A 6-year multicenter retrospective adult case-control study.

BACKGROUND: Beta-lactams (BLs) are commonly used antibiotics and leading causative agents of drug-induced anaphylaxis. Few studies on the culprit drugs and risk factors of BL-induced anaphylaxis are available. Our goal was to evaluate the culprit drugs and compare the risk factors in patients with BL-induced anaphylaxis to matched tolerant controls in a hospital setting. METHODS: We retrospectively enrolled all patients who developed anaphylaxis from intravenous BL during hospitalization from 9 Korean hospitals. We compared clinical parameters between patients with BL-induced anaphylaxis and 4-fold BL-tolerant controls matched by age, sex, BL use, and the purpose of BL administration. RESULTS: Seventy-four cases of BL-induced anaphylaxis and 296 BL-tolerant controls were enrolled. Cephalosporin accounted for 77% of total BL-induced anaphylaxis, and the top derivatives were ceftriaxone (23.0%), cefazedone (10.8%), and cefbuperazone (9.5%). Among penicillin derivatives, piperacillin (16.2%) was the most common, followed by ampicillin (2.7%). History of drug allergy (odds ratio [OR], 19.91; 95% confidence interval [CI] 5.33-74.44), previous exposure to the causative BL (OR, 7.71; 95% CI, 1.62-36.76), and concurrent administration of angiotensin-converting enzyme inhibitors (ACEIs) (OR, 5.97; 95% CI, 1.28-27.91) were independent risk factors associated with BL-induced anaphylaxis. Food allergy (OR, 13.93; 95% CI 1.31-148.9) and previous exposure to BL (OR, 6.59; 95% CI, 1.30-33.31) were identified as risk factors for cephalosporin-induced anaphylaxis. CONCLUSIONS: To prevent BL-induced anaphylaxis, attention should be paid to histories of drug or food allergy, previous exposure to BLs, and ACEI use. The risk factors and clinical outcomes might vary according to the BL classes.

Finding the Optimal Alternative for Immediate Hypersensitivity to Low-Osmolar Iodinated Contrast.

OBJECTIVES: Avoiding culprit agents is recommended for subjects who have had previous hypersensitivity reaction (HSR) to low-osmolar contrast media (LOCM). However, the guidelines for choosing optimal alternatives have not been determined. We investigated the outcomes of reexposure in patients with previous immediate HSRs to provide a safe option. MATERIALS AND METHODS: The outcomes of reexposure were assessed in a cohort with previous LOCM-associated HSR based on skin testing results and the presence of a common N-(2,3-dihydroxypropyl) carbamoyl side chain. RESULTS: Among 482 skin tests, 38.7% (31/80), 45.8% (99/216), and 64.0% (119/186) of mild, moderate, and severe index HSRs showed positivity to at least 1 LOCM, of which 62.8% showed positivity to at least 2 different LOCM. The overall recurrent HSRs were reduced from 43.8% upon reexposure to the culprit LOCM to 12.3% upon using nonculprit skin test negative LOCM (P = 0.004); those with severe index HSRs exhibited a significant reduction (11.3% vs 100%), but those with non-severe HSRs to LOCM did not. In subjects with severe index HSRs, the skin test cross-reactivity between LOCM was associated with sharing the common side chain (20.7% vs 11.5%, P = 0.003), and the recurrence rate of HSRs was effectively reduced by avoiding the common side chain (24.0% vs 7.8%, P = 0.039). However, these differences were not observed in those with non-severe index HSRs. CONCLUSIONS: In patients who experienced a severe index HSR to LOCM, skin test negative LOCM without a common side chain could be suggested as an option for safe reexposure.

A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.

BACKGROUND: Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization. OBJECTIVE: To investigate the efficacy and safety of a nondilution, 1-bag protocol in comparison with a conventional multi-bag protocol for desensitization of patients with paclitaxel hypersensitivity. METHODS: Patients who underwent paclitaxel desensitization between 2011 and 2018 were analyzed in this retrospective cohort study. The completion rate, time to completion, and occurrence and severity of breakthrough reaction (BTR) between a 1-bag protocol and a multi-bag protocol were compared. RESULTS: A total of 211 desensitization procedures were performed, of which 207 procedures (98.1%) were completed successfully. The administration time was significantly shorter in the 1-bag protocol group compared with the conventional multi-bag protocol group (266.0 ± 149.3 minutes vs 484.2 ± 178.6 minutes, P < .05) without differences in the completion rate (97.6% vs 98.9%, P = .645), the incidence of BTR (16.1% vs 27.6%, P = .778), and the proportion of severe BTR (2.6% vs 5.7%, P = .134). CONCLUSIONS: A nondilution, 1-bag protocol is noninferior to a multi-bag rapid desensitization protocol and can be a safe and effective option for paclitaxel desensitization.

Acute Adverse Reactions to Nonionic Iodinated Contrast Media: A Meta-Analysis.

OBJECTIVES: We aimed to meta-analytically compare the incidence of acute adverse reactions (AARs) to nonionic iodinated contrast media (ICM) according to the type of ICM in patients who underwent radiologic examinations with administration of ICM via intravascular route. MATERIALS AND METHODS: A systematic literature search identified studies evaluating the incidence of AARs to 7 nonionic ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, ioversol, and iodixanol) with extractable outcomes. These outcomes were pooled using a random-effects model, and the effect of ICM type on the incidence of overall and severe AARs was evaluated using meta-regression analysis. RESULTS: Thirty studies with 1,360,488 exposures to ICM were included. The pooled incidences of overall and severe AARs to nonionic ICM were 1.03% (95% confidence interval [CI], 0.81%-1.30%; I = 0.99) and 0.0141% (95% CI, 0.0108%-0.0183%; I = 0.56), respectively. Iomeprol had the highest overall AAR incidence (1.74%; 95% CI, 0.79%-3.76%; I = 0.99), followed by iohexol (1.21%; 95% CI, 0.67%-2.17%; I = 0.99), iopamidol (1.10%; 95% CI, 0.60%-2.03%; I = 0.99), ioversol (0.88%; 95% CI, 0.43%-1.83%; I = 0.96), iodixanol (0.85%; 95% CI, 0.36%-1.95%; I = 0.99), iopromide (0.82%; 95% CI, 0.43%-1.55%; I = 0.99), and iobitridol (0.77%; 95% CI, 0.36%-1.62%; I = 0.99). Multivariable meta-regression analysis revealed that study design (P = 0.0014) and premedication (P = 0.0230) were statistically significant determinants affecting the incidence of overall AARs. Iodinated contrast media type did not affect the incidence of overall and severe AARs (P = 0.1453 and 0.4265, each). CONCLUSIONS: The varying pooled incidences of overall and severe AARs to specific types of nonionic ICM do not remain as significant after adjusting confounders. Our results may support nonrestriction of certain types of nonionic ICM in the context of AAR avoidance.

The Presence of HLA-B75, DR13 Homozygosity, or DR14 Additionally Increases the Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in HLA-B*58:01 Carriers.

BACKGROUND: Although HLA-B*58:01 is a well-known risk factor for the development of allopurinol-induced severe cutaneous adverse reactions (SCARs), most of the HLA-B*58:01 carriers do not suffer from SCARs despite a long-term use of allopurinol. This suggests that there are other risk factors that determine the fate of HLA-B*58:01 carriers. OBJECTIVE: The aim of this study was to investigate the additional genetic factors that increase the risk of allopurinol-induced SCARs in HLA-B*58:01 carriers. METHODS: The incidence of allopurinol-induced SCARs was investigated according to coexisting HLA alleles in all subjects with HLA-B*58:01 who took allopurinol between 2003 and 2017. The allopurinol tolerant group was defined as a group who took allopurinol for more than 60 days without developing hypersensitivity and was compared with the allopurinol-induced SCAR group. RESULTS: Among the retrospective cohort consisting of 367 HLA-B*58:01 carriers treated with allopurinol, 11 (3.0%) were diagnosed with allopurinol-induced SCARs. When HLA-B75, DR13 homozygosity, or DR14 was present, the incidence of SCARs increased up to 22.2% (odds ratio [OR], 19.568; P = .015), 20.0% (OR, 38.458; P = .001), and 10.7% (OR, 19.355; P = .004), respectively. Among the 153 HLA-B*58:01 carriers with chronic renal insufficiency (CRI), the incidence of SCARs doubled to 6.5% and further increased to 40%, 30%, and 37.5% in the presence of HLA-B75, DR13 homozygosity, or DR14, respectively. CONCLUSIONS: Secondary screening with HLA-B75, DR13 homozygosity, and DR14 in addition to primary screening with HLA-B*58:01 would enable a more accurate prediction of SCAR occurrence, especially in patients with CRI.

Immediate Mild Reactions to CT with Iodinated Contrast Media: Strategy of Contrast Media Readministration without Corticosteroids.

Purpose To evaluate premedication protocols involving administration of antihistamine and multidose corticosteroid that have been widely used in prevention of recurrent hypersensitivity reactions (HSRs) to iodinated contrast media (ICM); an evidence-based optimal preventive strategy customized for patients with mild cases has not yet been established. Materials and Methods The outcomes of patients with mild HSR who subsequently underwent contrast material-enhanced computed tomography (CT) between January 2012 and December 2015 were analyzed. For premedication, 4 mg of chlorpheniramine was intravenously administered 30 minutes prior to reexposure to ICM. Logistic regression with generalized estimating equations was used to determine the relationship between premedication and recurrence rate. Results A total of 1178 patients with mild immediate HSR were reexposed to ICM 3533 times. Among these patients, 1056 patients experienced allergylike reactions and 122 patients developed gastrointestinal reactions. With reexposure to the culprit agent without premedication, the recurrence rate was 31.1% (85 of 273 examinations). The recurrence rate decreased to 12% (105 of 872 examinations; P < .001) by only changing the culprit agent and to 7.6% (148 of 1947 examinations; P < .001) by using the combination of changing the ICM and antihistamine premedication. Changing the ICM plus antihistamine premedication was also helpful in reducing the recurrence of gastrointestinal symptoms from 16.1% to 1.8% (P = .020). However, despite changing of the ICM, some combinations of ICM did not show a prophylactic effect. Conclusion A combination of changing the culprit agent and antihistamine premedication resulted in the best preventive outcome for patients with mild immediate HSR. The optimal choice of substitute ICM could be individualized according to the culprit agent.

Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study.

BACKGROUND: Oxaliplatin-related hypersensitivity reactions (HSRs), which can be life threatening, have introduced a dilemma regarding the use of chemotherapeutic agents. Because repeated exposure to oxaliplatin may increase the risk of sensitization, patients with a history of prior asymptomatic exposure require risk-stratified care. OBJECTIVE: This study aimed to elucidate the incidence and risk of oxaliplatin HSRs in patients with a history of asymptomatic prior exposure. METHODS: We performed a prospective observational study of patients who completed oxaliplatin-based chemotherapy between March 2013 and January 2015. Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity, eosinophil counts, and premedication were reviewed to assess the risk factors. RESULTS: A total of 793 patients were enrolled, among whom 148 (18.7%) experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients but increased to 31.9% among those with a history of asymptomatic exposure and 75.0% among those with a history of oxaliplatin HSRs during the previous exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the previous HSR group, followed by the previous asymptomatic exposure and nonexposure groups. The HSR severity also differed according to the previous exposure history and HSRs. In the multivariate analysis, prior exposure to oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and a longer oxaliplatin-free interval (≥36 months; OR, 4.85; 95% CI, 1.60-14.37) were independent risk factors for HSRs. CONCLUSIONS: Previous exposure to oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent HSR episodes, even if prior therapy was well tolerated.

A population-based case-control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate.

BACKGROUND: Studies on the risk of osteoporotic fractures related to the use of proton pump inhibitors (PPIs) have been inconsistent. One recent cohort study reported that there was an interaction between PPIs and bisphosphonates (BPs). Thus we performed a case-control study aimed at evaluating the risk of hip fractures related to PPIs and exploring the interaction between PPIs and BPs. METHODS: A case-control study was performed using the Korean Health Insurance Review and Assessment Service database from 2005 January to 2006 June. The cases were all incident hip fractures identified from July 2005 to June 2006, and up to four controls were matched to each case by age, gender, and osteoporosis. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and its 95 % confidence intervals. RESULTS: A total of 24,710 cases were identified and 98,642 controls were matched to the cases. The aOR and its 95 % CI of hip fractures related to the use of PPIs was 1.34 (95 % CI 1.24-1.44). When the study participants were stratified according to BP use, the aOR was 1.30 (95 % CI 1.19-1.42) in BP non-users, which was significantly different from the 1.71 (95 % CI 1.31-2.23) of BP users. Only BP users showed a decreasing tendency toward fracture risk as exposure to PPI became less recent, and a trend of increasing risk with increasing cumulative doses. CONCLUSIONS: Our results suggest that the mechanism for increased risk of hip fracture by PPIs may arise mainly from interaction of BP and PPIs.

Zolpidem use and risk of fracture in elderly insomnia patients.

OBJECTIVES: To evaluate the risk of fractures related with zolpidem in elderly insomnia patients. METHODS: Health claims data on the entire South Korean elderly population from January 2005 to June 2006 were extracted from the Health Insurance Review and Assessment Service database. We applied a case-crossover design. Cases were defined as insomnia patients who had a fracture diagnosis. We set the hazard period of 1 day length prior to the fracture date and four control periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date. Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the case-crossover design. Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis. The odds ratios and their 95% confidence intervals (CIs) were estimated for the risk of fracture related to zolpidem. RESULTS: One thousand five hundred and eight cases of fracture were detected in insomnia patients during the study period. In our data, the use of zolpidem increased the risk of fracture significantly (adjusted odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between benzodiazepine hypnotics and the risk of fracture was not statistically significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup. CONCLUSIONS: Zolpidem could increase the risk of fracture in elderly insomnia patients. Therefore zolpidem should be prescribed carefully and the elderly should be provided with sufficient patient education.