Twisted Wonderland is a popular mobile game developed by Aniplex and Walt Disney Japan. It takes place in a magical world called Twisted Wonderland, where players can attend the prestigious Night Raven College and interact with various Disney villains. One of the unique aspects of the game is the concept of magical data. **Magical data** in Twisted Wonderland refers to the elemental affinity and attributes that each character possesses. These attributes, known as "Magicalities," determine the skills, combat abilities, and strengths of the characters. There are six different types of Magicalities: Heartslabyul (water), Savanaclaw (wind), Octavinelle (light), Scarabia (space), Pomefiore (gravity), and Ignihyde (fire).
A patient is dropping off a prescription for magic mouthwash
Two medicated mouthwashes led to reductions in oral mucositis pain for head and neck cancer patients treated with radiotherapy, but not at a level deemed clinically important, a randomized phase III study found. Within 4 hours of radiotherapy, pain from oral mucositis dropped by 11.7 points (as defined by the area under the curve) with a diphenhydramine-lidocaine-antacid rinse -- or "magic mouthwash" -- and 11.6 points with a doxepin mouthwash, compared with 8.7 points with placebo, reported Robert C. Miller, MD, MS, MBA, of the University of Maryland School of Medicine in Baltimore, and colleagues.
Over 80% of radiotherapy- and chemoradiotherapy-treated head and neck cancer patients develop the painful and debilitating complication, with severe symptoms requiring hospitalization and feeding tubes, they explained. Systemic analgesics and mouthwashes are frequently used to manage the condition. "For the diphenhydramine-lidocaine-antacid mouthwash, the current study provided the first evidence that the mouthwash appeared to be effective for short-term oral mucositis–related pain resulting from radiotherapy," Miller's group wrote in JAMA. "However, the mean differences in pain reduction by the area under the curve for both treatment intervention mouthwashes were less than the minimal clinically important difference of 3.5 points." Compared with placebo, diphenhydramine-lidocaine-antacid led to a 3.0-point improvement (95% CI 0.1-5.9, P=0.004) while the doxepin mouthwash led to a 2.9-point improvement (95% CI 0.2-6.0, P=0.02). "These data tell us that magic mouthwash (or doxepin) is not the sole answer to managing mucositis -- physicians should not prescribe magic mouthwash and expect magic!" Arjun Gupta, MD, of the Sidney Kimmel Comprehensive Cancer Center in Baltimore, told MedPage Today in an email. "We have very few drugs to treat [these] patients in great suffering, and we need more drugs in well-designed trials to urgently address this question."
Gupta, who was not involved in the research, previously co-authored a perspective calling into question the routine use of magic mouthwash for oral mucositis, with issues ranging from the limited efficacy, potential for high out-of-pocket costs, among other concerns. "In the real world, there is no fixed formula for magic mouthwash. Most providers do not know the contents or concentrations of the ingredients in these mixed-medication formulations," he said. "They could also contain unnecessary and harmful ingredients such as steroids and antibacterials/antifungals. How many other drugs do physicians prescribe without knowing the contents or concentration?"
"Steroids, especially in a patient with dry mouth, may induce local secondary fungal infections that exacerbate oral pain," said Sharon Elad, DMD, MSc, of the University of Rochester Medical Center in New York, and Noam Yarom, DMD, of Tel Aviv University in Israel, in an editorial that accompanied the study. "Furthermore, the use of a single term for multiple compounds hampers clear communication between professionals, and, ideally, the term should be uniform and describe the actual active ingredients."
For this reason, said Gupta, the American Academy of Nursing recommends against use of mixed-medication mouthwash for managing oral mucositis. Gupta also noted that previous research has shown similar efficacy between a magic mouthwash similar to that used in this Alliance study, chlorhexidine, and a salt and soda mix. "Given the ease of preparation at home and almost no cost (1 teaspoon of salt and sodium bicarbonate each in 1 liter of water), salt and soda mouthwash is often prescribed by physicians," he said, adding that had this been used in place of the placebo, or as a fourth study arm, it might have demonstrated equivalence or superiority over the investigational agents. Drowsiness, stinging or burning, and unpleasant taste were examined as secondary outcomes on scales ranging from best to worst (0-10). With the doxepin rinse compared with placebo: drowsiness (1.5 points higher, P=0.03) and unpleasant taste (1.5 points higher, P=0.002) were worse than placebo. No significant differences were seen between the diphenhydramine-lidocaine-antacid and placebo groups.
- Doxepin: 79.5%, P=0.14
- Diphenhydramine-lidocaine-antacid: 85.5%, P=0.02
"This suggests that a subgroup of patients may have experienced meaningful benefits from the diphenhydramine-lidocaine-antacid mouthwash," the editorialists wrote.
For the Alliance A221304 study, Miller's team randomized 275 patients (1:1:1) at 30 institutions in the U.S. from 2014 to 2016. All patients had a minimum pain score of 4 (out of 10). In all, 92 patients received the 25-mg doxepin mouthwash (in a 5-mL solution), 92 received a 5-mL placebo mouthwash consisting of water and Ora-Sweet SF (2.5 mL each), and 91 received a 5-mL solution of 12.5 mg diphenhydramine, 2% lidocaine, and an antacid (200 mg of aluminum hydroxide, 200 mg of magnesium hydroxide, and 20 mg of simethicone).
Limitations of the study included the fact that it was only designed to assess pain at up to 4 hours after administration of the mouthwash, while post-radiotherapy pain can persist for days.
This study was funded by the Alliance for Clinical Trials, the National Cancer Institute, and the Mayo Clinic Symptom Intervention Program.
Miller reported non-financial support from CutisPharma.
Elad reported relationships with Falk Pharma, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer, and the International Society of Oral Oncology.
Gupta reported no disclosures.
Source Reference: Sio TT, et al "Effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo on radiotherapy-related oral mucositis pain: The Alliance A221304 randomized clinical trial" JAMA 2019; 321(15): 1481-1490.
Source Reference: Elad S, Yarom N "The search for an effective therapy and pain relief for oral mucositis" JAMA 2019; 321(15): 1459-1461.
Beyond-use dating of lidocaine alone and in two "magic mouthwash" preparations
Purpose: Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined.
Methods: Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness.
Results: Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration.
Conclusion: A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes.
Keywords: chromatography; drug stability; high pressure liquid; lidocaine; magic mouthwash; mucositis.
Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
There are six different types of Magicalities: Heartslabyul (water), Savanaclaw (wind), Octavinelle (light), Scarabia (space), Pomefiore (gravity), and Ignihyde (fire). Each character in the game belongs to one of these Magicalities, and they can use spells and abilities associated with their respective attributes. The magical data of the characters plays a crucial role in battles and challenges in the game.
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Each character has unique skills and spells that are based on their Magicalities. For example, Heartslabyul characters excel in water-based spells and healing abilities, while Ignihyde characters are experts in fire magic and offensive spells. Understanding and utilizing the magical data of characters strategically can greatly enhance the player's performance and chances of success in battles. In addition to their Magicalities, each character also possesses a unique Grim, a partner creature that provides additional buffs and abilities. These Grims have their own magical data, which can further enhance the character's capabilities in battles. As players progress through Twisted Wonderland, they can collect and level up different characters with various magical data. This provides opportunities for strategy and customization, as players can form teams with well-balanced Magicalities and abilities that complement each other. Experimenting with different combinations of characters and their magical data adds depth and replayability to the game. Overall, the concept of magical data in Twisted Wonderland adds a layer of depth and strategy to the gameplay. It allows players to explore different magical affinities and utilize unique spells and abilities associated with them. Understanding and leveraging the magical data of characters is vital for success in battles and challenges, making it an essential aspect of the game..
Reviews for "Unlocking Hidden Features Through Twisted Wonderland's Magical Data"
1. Emily - 2 stars
I was really excited to play "Twisted Wonderland Magical Data" as I had heard great things about it. However, I was extremely disappointed with the game. The storyline was confusing and didn't make much sense. The characters were also quite bland and lacked depth. Additionally, the graphics were subpar and looked outdated. Overall, I found the game to be boring and a waste of my time.
2. Jacob - 1 star
I cannot express how much I dislike "Twisted Wonderland Magical Data". The game is full of technical glitches and bugs that make it almost unplayable. It constantly crashes, freezes, and lags, which is incredibly frustrating. The gameplay itself is repetitive and offers no real challenge. The developers really need to fix these issues if they want people to enjoy this game.
3. Sarah - 2 stars
I was so excited to dive into the magical world of "Twisted Wonderland Magical Data", but it fell flat for me. The game had so much potential, but it was let down by its lackluster storyline. I found myself losing interest quickly as there wasn't much substance to the plot. The characters were also forgettable and didn't leave a lasting impression. Overall, I was disappointed with the game and wouldn't recommend it to others.
4. Michael - 3 stars
"Twisted Wonderland Magical Data" had some promising elements, but it didn't quite live up to my expectations. The gameplay mechanics were clunky and unintuitive, making it frustrating to navigate through the various levels. The graphics were decent, but they lacked the wow factor that I was hoping for. Additionally, the in-app purchases felt forced and took away from the overall gaming experience. Overall, the game had some potential, but it didn't quite hit the mark for me.
5. Ashley - 2 stars
I found "Twisted Wonderland Magical Data" to be a disappointment. The storyline was predictable and lacked originality. The dialogue was also quite cringe-worthy at times. The game felt like a money-grab with its constant push for in-app purchases, which made it difficult to enjoy the gameplay. Overall, I was left feeling unsatisfied and wouldn't recommend this game to others.