AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2578-8949/020
*Corresponding Author: Luke Jackson, Department of Dermatology, Italy.
Citation: Luke Jackson, Jonathan Noah, Miguel Seth, and Collin Jared , Skin Care Using Heparinoid Creams for Long-Term Treatment with Oxybutynin Transdermal Patches without Skin Irritation in Elderly OAB Patients. J .Dermatology and Dermatitis. Doi: 10.31579/2578-8949/020
Copyright: © 2018 Luke Jackson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 22 January 2018 | Accepted: 20 February 2018 | Published: 26 February 2018
Keywords: heparinoids; overactive bladder; skin care; transdermal patch
Background: Overactive bladder is an age-related urologic disease. An oxybutynin transdermal patch is used to treat overactive bladder; however, long-term use is not advised because of potential adverse reactions at the site of application. The present study aimed to investigate the advantages of administering a combination of heparinoid cream and oxybutynin transdermal patch treatment for overactive bladder in elderly patients.
Methods: Eight patients (>65 years of age) with overactive bladder were included. The heparinoid cream was applied topically for 1 week, and skin hydration and transepidermal water loss were quantified before and after application. Thereafter, patients were treated with a combination of an oxybutynin transdermal patch and a heparinoid cream for 12 weeks, and the sites of application were monitored for adverse reactions. Clinical effects of the combinatorial treatment were assessed based on the overactive bladder symptom score.
Results: Application of the heparinoid cream did not decrease transepidermal water loss, but increased skin hydration and improved dryness. Oxybutynin transdermal patch therapy was not interrupted because no skin irritation was observed at the site of application for 12 weeks, and the overactive bladder symptom score decreased significantly (p<0.05).
Conclusions: Combination treatment with an oxybutynin transdermal patch and a heparinoid cream improved treatment outcomes, suggesting that skin hydration with heparinoid cream is a promising treatment method to ensure appropriate use of oxybutynin transdermal patches in elderly patients with overactive bladders.
The incidence of overactive bladder (OAB) has increased in Japan because of rapid aging of the population [1]. As frequent urination, a major symptom of OAB, decreases the quality of life of patients with OAB [2], therapeutic drugs including muscarinic antagonists and β3-adrenoceptor agonists are administered clinically to improve bladder urine retention. Currently, selective muscarinic antagonists are used as first-line drugs to treat OAB [3] and have been developed as an alternative to oral administration of oxybutynin in order to enhance pharmacotherapeutic tolerance.
The oxybutynin transdermal patch is a sustained-release drug formulation containing oxybutynin hydrochloride [4]. Production of N-desethyloxybutynin (DEO), an active metabolite of oxybutynin, is lower with transdermal patches than with oral formulations because oxybutynin is absorbed through the skin, thereby avoiding the hepatic first-pass effect [5]. Anticholinergic effects of DEO increase therapeutic efficacy; however, they also cause side effects including dry mouth and constipation [6]. Use of oxybutynin transdermal patches maintains DEO at low levels during OAB treatment without affecting the activities of daily living [7]. Long-term use of oxybutynin transdermal patches is associated with an increased incidence of skin irritation at the site of application [8]. Therefore, skin conditions of patients with OAB should be evaluated before applying oxybutynin transdermal patches.
The skin of elderly individuals is often dry because of reduced sebum secretion and hydration of the stratum corneum [9,10]. Dry skin is associated with desquamation of the stratum corneum, erythema, and itching [11]. As a transdermal patch should not be applied to the site of application where an adverse reaction has occurred, skin care is important during treatment with transdermal patches. Although moisturizers are commonly used for skin care [12], in particular, a heparinoid cream is expected to decrease skin irritation caused by the transdermal patch to a greater extent because it has high skin hydrating effects [13]. Therefore, use of heparinoid cream would decrease skin irritation caused by oxybutynin transdermal patches and improve treatment adherence. Previously, we reported that treatment with heparinoid cream before applying oxybutynin transdermal patches significantly relieved skin damage occurring after application of oxybutynin transdermal patches [14]. However, the effects of heparinoid cream in OAB treatment with oxybutynin transdermal patches have not been validated clinically.
The present study was carried out to investigate the effects of a combination of heparinoid cream with an oxybutynin transdermal patch in elderly OAB patients.
This prospective observational study was performed at the Nagae Prostate Care Clinic according to the procedure depicted in Figure 1. After selecting participants based on the eligibility criteria described in the Participants subsection, heparinoid cream (Hirudoid® soft ointment; Maruho Co., Ltd., Japan) was applied to the skin for 13 weeks. Before application of the heparinoid cream and oxybutynin transdermal patch (NEOXY® TAPE 73.5 mg; Hisamitsu Pharmaceutical Co., Inc., Tokyo, Japan), skin hydration and transepidermal water loss (TEWL) were evaluated at the site of application. An oxybutynin transdermal patch was applied for 12 weeks, and its efficacy and adherence were evaluated every 2 weeks.
Study participants were selected from among OAB patients of both sexes, aged >65 years, who consulted the Nagae Prostate Care Clinic from March to July, 2016. Patients with skin diseases; uroschesis; closed-angle glaucoma; pyloric, duodenal, or intestinal tract blockage; paralytic ileus; gastric or intestinal atony; myasthenia gravis; and those with a history of oxybutynin hydrochloride hypersensitivity were excluded.
Heparinoid cream and oxybutynin transdermal patches were applied based on the schedule depicted in Figure 2. The heparinoid cream (approximately 1 g) was applied twice a day for 13 weeks to the lower abdomen, femoral area, and lower back area of the participants. After 1 week, treatment with oxybutynin patches was initiated. An oxybutynin transdermal patch was applied for 24 h to the right side of the lower abdomen area (Figure 2 {B a}) 1 h after application of the heparinoid cream. From the following day, the oxybutynin transdermal patch was applied consecutively to the skin areas, as illustrated in Figure 2 (B b-f ).
Skin condition in the lower abdomen, femoral area, and lower back of the participants was evaluated before application of the heparinoid cream and oxybutynin transdermal patches, as shown in Figure 2. Skin hydration and TEWL were evaluated using Corneometer CM825 and Tewameter TM300 (Courage and Khazaka Electronic DmbH, Cologne, Germany), respectively, in a room at 45-55% humidity and at 20–25°C.
OAB severity was evaluated on the basis of the OABSS, assessed every 2 weeks from the initiation of oxybutynin transdermal patch treatment (week 2). A reduction in OABSS of >3 points during treatment period was considered to indicate effective treatment according to the evaluation method described by Gotoh et al. [15].
All data are presented as the mean±standard deviation (SD) values. Statistical significance of differences between group means was determined using the Mann–Whitney U test. A P-value less than 0.05 indicated statistical significance.
This study was approved by the ethics committee of Suzuka University of Medical Science (approval number: 2016-3-256) and written consent was obtained from all participants in accordance with the tenets of the Declaration of Helsinki.
Effects of heparinoid cream on skin hydration and TEWL
No significant differences were observed in skin hydration at the lower back area after application of the heparinoid cream; however, skin hydration in the lower abdomen and femoral areas improved significantly (Figure 3). No differences were observed in TEWL levels (Figure 4).
No dermatological side effects were observed in any of the patients during treatment with the oxybutynin transdermal patch. The average OABSS decreased from 7.5 points to 4.63 points after 12 weeks of treatment (Figure 5), with 5 of 8 patients (70%) reporting a reduction of >3 points in the OABSS.
In this study, we investigated the effect of heparinoid cream application on the outcomes of treatment with an oxybutynin transdermal patch in elderly patients with OAB. To fulfill our study objective, 10 patients were assessed for eligible skin barrier function. Two patients were excluded because of an insufficient duration of application of the heparinoid cream and oxybutynin transdermal patch. Finally, eight patients (6 males and 2 females) were included in the study.
OAB treatments using oral anticholinergic drugs decrease the quality of life of patients because of anticholinergic side effects such as dry mouth, drowsiness, and coprostasis [16,17]. Oxybutynin transdermal patches have a few associated anticholinergic side effects and are important in treating OAB while maintaining the quality of life of patients. However, effective treatments with oxybutynin transdermal patches are discontinued after 3 months in approximately 64% of cases [18]. Furthermore, Yamaguchi et al. reported that mild reactions occurred at the site of application in 30.3% of elderly patients treated with an oxybutynin transdermal patch [8]. Recently, sustained application of heparinoids has effectively prevented skin irritation at the site of application of transdermal patches [19]. No oxybutynin transdermal patch-associated skin irritation was observed during this study. Our results revealed a reduction in the incidence of adverse reactions at the site of application and higher continuity rates than those reported previously. The OABSS rates four symptoms: daytime urinary frequency, nighttime urinary frequency, urgency, and urgency incontinence; a reduction in the total OABSS reflects effective OAB treatment. In this study, the mean OABSS after 12-week treatment was 4.63 points. As the mean OABSS reported after the oral administration of propiverine hydrochloride and oxybutynin hydrochloride was 4.65 points [20], the therapeutic effects of the combination of the oxybutynin transdermal patch and heparinoid cream explored in this study were considered adequate. These results suggest that application of heparinoid cream effectively prolongs the period of safe use of oxybutynin transdermal patch for OAB treatment without compromising therapeutic effects.
The onset of skin irritation at the site of application of transdermal patches depends on the state of the skin surface [21]. The skin of elderly individuals is easily affected by external stimuli such as cold or dry climate and use of soaps and harsh cleansers because of reduced barrier function and skin hydration caused by aging-related reduction in sebum secretion [22]. Hence, it was speculated that heparinoid cream inhibited skin irritation after application of oxybutynin transdermal patches by moisturizing the dry skin of elderly patients. However, after 1 week of heparinoid cream application, TEWL, which is indicative of skin barrier function, remained unchanged, although skin hydration increased significantly. TEWL was previously reported to decrease after application of a heparinoid-based moisturizer [23]. However, increased TEWL was reported immediately after the application of a moisturizer because of evaporation of water in the formulation [24]. The barrier function of the stratum corneum also reportedly improved after 1 week of application of the heparinoid cream [25]. The dosing time for the eight patients was limited to 1–2 h because the participants in this study were outpatients at Nagae Prostate Care Clinic and a consistent application time was required for the heparinoid cream and oxybutynin transdermal patch for all patients. Hence, the dosing interval of the medications had to be set to 1 h, although TEWL was still quantified accurately. Therefore, high TEWL values observed in this study probably resulted from the evaporation of water from the heparinoid cream, considering that skin hydration function was improved.
Currently, the use of transdermal patches on the skin treated with creams, lotions, or powders is often not feasible owing to decreased skin adhesion. Takai et al. reported that skin adhesiveness of lidocaine tapes was not affected upon application of a heparinoid-based moisturizer [19]. Similarly, in this study, adhesion of oxybutynin transdermal patches was not affected by prior application of the heparinoid cream. Additionally, Björklund et al. reported that skin hydration increased its permeability to metronidazole [26]. Since prior application of the heparinoid cream significantly increased skin hydration in this study, transdermal absorption of oxybutynin hydrochloride may have been altered. Further fundamental animal studies evaluating transdermal absorption of oxybutynin hydrochloride after application of the heparinoid cream are required to adequately assess the proposed use of oxybutynin transdermal patches in combination with heparinoid cream.
Skin care using heparinoid creams has allowed for long-term treatment with oxybutynin transdermal patches without skin irritation in elderly OAB patients. This has also led to fewer side effects and prolonged treatment with stable pharmacological effects. As this technique has circumvented adverse dermatological effects associated with transdermal patches, it has potential applications in general utility for transdermal drug delivery. Drug therapy with transdermal patches has become increasingly important in recent years as the elderly population is increasing. Evaluation of the effects of moisturizers in decreasing skin irritation caused by transdermal patches plays an important role in drug treatment for elderly patients.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
