High Patient Compliance Research Articles

Role of 3D Printing in the Development of Biodegradable Implants for Central Nervous System Drug Delivery.

Increased life expectancy has led to a rise in age-related disorders including neurological diseases such as Alzheimer's disease and Parkinson's disease. Limited progress has been made in the development of clinically translatable therapies for these central nervous system (CNS) diseases. Challenges including the blood-brain barrier, brain complexity, and comorbidities in the elderly population are some of the contributing factors toward lower success rates. Various invasive and noninvasive ways are being employed to deliver small and large molecules across the brain. Biodegradable, implantable drug-delivery systems have gained lot of interest due to advantages such as sustained and targeted delivery, lower side effects, and higher patient compliance. 3D printing is a novel additive manufacturing technique where various materials and printing techniques can be used to fabricate implants with the desired complexity in terms of mechanical properties, shapes, or release profiles. This review discusses an overview of various types of 3D-printing techniques and illustrative examples of the existing literature on 3D-printed systems for CNS drug delivery. Currently, there are various technical and regulatory impediments that need to be addressed for successful translation from the bench to the clinical stage. Overall, 3D printing is a transformative technology with great potential in advancing customizable drug treatment in a high-throughput manner.

Immunomodulatory effect and safety of TNF-α RNAi mediated by oral yeast microcapsules in rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that requires long-term treatment and monitoring. Inhibition of inflammatory gene expression by gene therapy is a significant breakthrough in RA treatment, but the lack of a safe and effective gene delivery system hinders its application. Since oral administration can significantly reduce wound infection caused by parenteral administration, it also has the advantages of high patient compliance and convenience. Therefore, oral administration may be the best option for the treatment of this chronic disease. In this study, we developed a novel oral drug system by delivering tumor necrosis factor-α (TNF-α) short hairpin RNA (shRNA) mediated by non-pathogenic yeast to evaluate its regulation of systemic immune inflammation and safety in RA. Non-pathogenic yeast can resist the destruction of the gastrointestinal acid-base environment and can be recognized by the intestinal macrophages and act on systemic inflammatory lesions. Oral administration of yeast-mediated TNF-α shRNA significantly reduced the expression of TNF-α predominant pro-inflammatory factors in intestinal macrophages and joint synovium, and up-regulated the expression of anti-inflammatory cytokine IL-10 and M2 macrophages, systematically regulating the inflammatory response. This yeast-mediated oral gene delivery system can not only significantly inhibit knee joint synovial inflammation, but also has no toxic effects on peripheral blood and major organs. Therefore, yeast-mediated oral delivery of TNF-α shRNA may be used as a novel gene therapy strategy to treat RA through immunomodulating the mononuclear phagocyte system from the intestine to the joint synovium, and ultimately regulating systemic and local immune inflammation, providing new ideas for the clinical treatment of RA.

Emerging Trends in the Use of Topical Antifungal-Corticosteroid Combinations.

A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin infections. Their many benefits, owing to their specific mechanism of action, include their ability to target the site of infection, enhance treatment efficacy and reduce the risk of systemic side effects. Their proven efficacy, and positioning in the treatment of fungal skin infections, is enhanced by high patient compliance, especially when appropriate vehicles such as creams, ointments and gels are used. However, inflammation as a result of fungal infection can often impede treatment, especially when combined with pruritus (itch), an unpleasant sensation that elicits an urge to scratch. The scratching that occurs in response to pruritus frequently accelerates skin damage, ultimately aggravating and spreading the fungal infection. To help overcome this issue, a topical antifungal-corticosteroid combination consisting of miconazole or terbinafine and corticosteroids of varying potencies should be used. Due to their inherent benefits, these topical antifungal-corticosteroid combinations can concomitantly and competently attenuate inflammation, relieve pruritus and treat fungal infection.

Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesis on drug bioavailability.

The oral route is the most common choice for drug administration because of several advantages, such as convenience, low cost, and high patient compliance, and the demand and investment in research and development for oral drugs continue to grow. The rate of dissolution and gastric emptying of the dissolved active pharmaceutical ingredient (API) into the duodenum is modulated by gastric motility, physical properties of the pill, and the contents of the stomach, but current in vitro procedures for assessing dissolution of oral drugs are limited in their ability to recapitulate this process. This is particularly relevant for disease conditions, such as gastroparesis, that alter the anatomy and/or physiology of the stomach. In silico models of gastric biomechanics offer the potential for overcoming these limitations of existing methods. In the current study, we employ a biomimetic in silico simulator based on the realistic anatomy and morphology of the stomach (referred to as "StomachSim") to investigate and quantify the effect of body posture and stomach motility on drug bioavailability. The simulations show that changes in posture can potentially have a significant (up to 83%) effect on the emptying rate of the API into the duodenum. Similarly, a reduction in antral contractility associated with gastroparesis can also be found to significantly reduce the dissolution of the pill as well as emptying of the API into the duodenum. The simulations show that for an equivalent motility index, the reduction in gastric emptying due to neuropathic gastroparesis is larger by a factor of about five compared to myopathic gastroparesis.

Validation of a Patient-Reported Outcome Measure for Moist Desquamation among Breast Radiotherapy Patients.

There has been an increasing interest in patient-reported outcome (PRO) measures in both the clinical and research settings to improve the quality of life among patients and to identify when clinical intervention may be needed. The primary purpose of this prospective study was to validate an acute breast skin toxicity PRO measure across a broad sample of patient body types undergoing radiation therapy. Between August 2018 and September 2019, 134 women undergoing adjuvant breast radiotherapy (RT) consented to completing serial PRO measures both during and post-RT treatment and to having their skin assessed by trained trial radiation therapists. There was high patient compliance, with 124 patients (92.5%) returning to the clinic post-RT for at least one staff skin assessment. Rates of moist desquamation (MD) in the infra-mammary fold (IMF) by PRO were compared with skin assessments completed by trial radiation therapists. There was high sensitivity (86.5%) and good specificity (79.4%) between PRO and staff-reported presence of MD in the IMF, and there was a moderate correlation between the peak severity of the MD reported by PRO and assessed by staff (rho = 0.61, p < 0.001). This prospective study validates a new PRO measure to monitor the presence of MD in the IMF among women receiving breast RT.

A novel framework to estimate cognitive impairment via finger interaction with digital devices.

Measuring cognitive function is essential for characterizing brain health and tracking cognitive decline in Alzheimer’s Disease and other neurodegenerative conditions. Current tools to accurately evaluate cognitive impairment typically rely on a battery of questionnaires administered during clinical visits which is essential for the acquisition of repeated measurements in longitudinal studies. Previous studies have shown that the remote data collection of passively monitored daily interaction with personal digital devices can measure motor signs in the early stages of synucleinopathies, as well as facilitate longitudinal patient assessment in the real-world scenario with high patient compliance. This was achieved by the automatic discovery of patterns in the time series of keystroke dynamics, i.e. the time required to press and release keys, by machine learning algorithms. In this work, our hypothesis is that the typing patterns generated from user-device interaction may reflect relevant features of the effects of cognitive impairment caused by neurodegeneration. We use machine learning algorithms to estimate cognitive performance through the analysis of keystroke dynamic patterns that were extracted from mechanical and touchscreen keyboard use in a dataset of cognitively normal (n = 39, 51% male) and cognitively impaired subjects (n = 38, 60% male). These algorithms are trained and evaluated using a novel framework that integrates items from multiple neuropsychological and clinical scales into cognitive subdomains to generate a more holistic representation of multifaceted clinical signs. In our results, we see that these models based on typing input achieve moderate correlations with verbal memory, non-verbal memory and executive function subdomains [Spearman’s ρ between 0.54 (P < 0.001) and 0.42 (P < 0.001)] and a weak correlation with language/verbal skills [Spearman’s ρ 0.30 (P < 0.05)]. In addition, we observe a moderate correlation between our typing-based approach and the Total Montreal Cognitive Assessment score [Spearman’s ρ 0.48 (P < 0.001)]. Finally, we show that these machine learning models can perform better by using our subdomain framework that integrates the information from multiple neuropsychological scales as opposed to using the individual items that make up these scales. Our results support our hypothesis that typing patterns are able to reflect the effects of neurodegeneration in mild cognitive impairment and Alzheimer’s disease and that this new subdomain framework both helps the development of machine learning models and improves their interpretability.

Carmustine: Promising Drug for Treatment of Glioma

Background: The treatment for glioma has challenging and survival rate is not more than one year after diagnosis. Carmustine is a non-specific antineoplastic agent that belongs to the nitrosourea group of compounds (bischlo-roethyl nitrosourea) and has various mechanisms of tumor cytotoxicity. Main body: It can alkylate reactive sites on nucleoproteins as an alkylating agent, interfering with DNA and RNA synthesis and DNA repair. It can create interstrand crosslink’s in DNA, preventing DNA replication and transcription. Under physiological conditions, carmustine undergoes spontaneous nonenzymatic decomposition, releasing reactive intermediates with alkylating and carbamoylating activities, which are thought to be responsible for carmustine’s anticancer and cytotoxic properties. Human gliomas are the for the most part kind of tumor for brain. Gliomas can be treated with a variety of chemotherapeutics, but carmustine has recently emerged as a promising treatment option. Conclusion: The adoption of a nose-to-brain medication delivery method has several advantages over efforts that try to breach the blood-brain barrier. The focused strategy also lowers the risk of cardiovascular harm. A significant advantage of nose to brain administration is the relatively high patient compliance. Research into new chemotherapeutic compounds and treatment delivery technologies is crucial for present and future patients

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies.

Ketoconazole (KTZ) is a potential oral antifungal agent to control systemic and local infections. This study addresses the impact of composition (tween 80 and compritol as CATO) and morphology on permeation (stomach, jejunum, and ileum) profiles of KTZ-loaded solid lipid nanoparticles (SLNs) in rats followed by in vivo pharmacokinetic prediction and simulation using GastroPlus. The selected formulations were characterized for size, size distribution, zeta potential, entrapment efficiency, total drug content, morphology, in vitro drug release, ex vivo permeation and drug deposition, penetration potential, and GastroPlus-based in vivo prediction in rats. The results showed that there was considerable impact of pH, composition (CATO and tween 80), size, total drug content, and entrapment efficiency on in vitro drug release and permeation across the stomach, jejunum, and ileum. Ex vivo findings suggested pH, composition, size, and permeability coefficient-dependent permeation of SLNs across the stomach, jejunum, and ileum. Confocal laser scanning microscopy (CLSM) confirmed a relatively high degree of penetration of the optimized formulation “K-SLN4” (66.1% across the stomach, 51.5% across the jejunum, and 47.9% across the ileum) as compared to KSUS (corresponding values of 21.7%, 18.2%, and 17.4%). Finally, GastroPlus predicted in vivo dissolution/absorption as 0.012 μg/mL of K-SLN4 as compared to KSUS (the drug suspension with 0.0058 μg/mL) and a total regional absorption of 80.0% by K-SLN4 as compared to 60.1% of KSUS. There was only an impact of dose on Cmax (maximum plasma concentration) and area under the curve (AUC) in rats. Thus, the present strategy could be a promising alternative to parenteral and topical delivery systems for long-term therapy against systemic and local mycoses with high patient compliance.

Effectiveness of Comfort Nursing Combined with Continuous Nursing on Patients with Colorectal Cancer Chemotherapy.

Purpose To analyze the application effect of continuous nursing combined with comfort nursing on patients with colorectal cancer chemotherapy and its influence on sleep quality and immune function. Methods The data of 96 patients with colorectal cancer in the Oncology Department of Peking Union Medical College Hospital from July 2018 to July 2020 were collected and randomized into the control group and study group according to the odd and even numbers, with 48 cases in each group. The control group received routine care during chemotherapy, and the study group implemented continuous care combined with comfort care. Results After intervention, the results were in favor of the study group than the control group with higher compliance, higher level of various immune indicators, higher quality of life scores, and higher nursing satisfaction rate. In addition, the Generalized Anxiety Disorder (GAD-7) scores and the average Pittsburgh Sleep Quality Index (PSQI) score of the study group after intervention was drastically lower than the control group (P < 0.001). Conclusion The implementation of continuous care combined with comfort care for patients with colorectal cancer undergoing chemotherapy can effectively improve sleep quality and quality of life, relieve anxiety, and yield high patient compliance, which is worthy of clinical promotion.

Application of Huangqi Guizhi Wuwu Decoction in Orthopaedics and Traumatology

AbstractThe Huangqi Guizhi Wuwu Decoction(HQGZWWT) is composed of Huangqi (Astragali Radix), Shaoyao (Paeoniae Radix Alba), Guizhi (Cinnamomi Ramulus), Shengjiang (Zingiberis Rhizoma Recens), and Dazao (Jujubae Fructus) which has various pharmacological anti-inflammatory, analgesic, antioxidant, antitumor, lipid-lowering, and immunity-regulating activities. It has certain advantages in the treatment of orthopaedic diseases, such as cervical spondylosis, scapulohumeral periarthritis, lumbar disc herniation, knee osteoarthritis, rheumatoid arthritis, myofascial pain syndrome, etc., with outstanding clinical efficacy, few adverse reactions, and high patient compliance. However, modern pharmacological researches on the whole prescription of HQGZWWT are insufficient and the therapeutic targets are not clear which needs further exploration. Besides, this prescription cannot treat all orthopaedic diseases, so we should adhere to the thinking of four diagnostics in traditional Chinese medicine (TCM), select prescriptions based on syndrome differentiation, closely follow the pathogenesis, innovate and expand its scope of application, reflect the application advantages of this prescription in orthopaedics and traumatology and improve the total clinical efficiency.

Dissolution from Ethylene Vinyl Acetate Copolymer Long-Acting Implants: Effect of Model Active Ingredient Size and Shape.

In recent pharmaceutical applications, an active pharmaceutical ingredient (API) can be mixed with a polymer material to yield a composite long-acting drug-delivery device. These devices boast higher patient compliance, localized drug delivery, and lower dosage concentrations, which can increase patient safety. As a laboratory-safe option, calcium carbonate (CaCO3) was used as a drug surrogate to mimic the release kinetics of a low-solubility API. The release of CaCO3 from a poly(ethylene vinyl acetate) (EVA) polymer matrix was studied in ultra-high-purity water. The geometry of CaCO3, along with the manufacturing technique, was manipulated to study the implications on surrogate drug release. It was found that injection molding proved to yield higher burst release, due to higher pressures achievable during manufacturing. The extrusion process can affect the surface concentration of the pharmaceutical ingredient when extruded through a water bath, resulting in a lower initial burst concentration. Regarding CaCO3 geometry, the particle size was more critical than the surface area in terms of CaCO3 release. Larger particles showed a higher release rate, though they also displayed higher variability in release. These data can be used to engineer specific release profiles when designing composite formulations and manufacturing methods for pharmaceutical-drug-delivery applications.

Formulation and Evaluation of Buccal Disintegrating Tablet of Anticonvulsant Drug

Oral and Buccal delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. To troubleshoot such problems a new dosage form known as Buccal and orally disintegrating tablet, has been developed which rapidly disintegrate and dissolve in saliva and then easily swallowed without need of water which is a major benefit over than conventional dosage form. In addition, patients suffering from dysphasia, motion sickness, repeated emesis and mental disorders prefer such preparation because they cannot swallow large quantity of water. the immediate release of medication and for instant release at desire location in which the drug is absorbed distributer and easily metabolized. e.g. To prepare and characterize buccal tablets of Gabapentin using different super disintegrants such as Cross povidon, PVP K30, Micro crystalline cellulose. This types of formulation of improving solubility of drug and development of Buccal drug delivery system.

Nucleus-Targeting Phototherapy Nanodrugs for High-Effective Anti-Cancer Treatment.

DNA is always one of the most important targets for cancer therapy due to its leading role in the proliferation of cancer cells. Phototherapy kills cancer cells by generating reactive oxygen species (ROS) and local hyperthermia under light. It has attracted extensive interest in the clinical treatment of tumors because of many advantages such as non-invasiveness, high patient compliance, and low toxicity and side effects. However, the short ROS diffusion distance and limited thermal diffusion rate make it difficult for phototherapy to damage DNA deep in the nucleus. Therefore, nucleus-targeting phototherapy that can destroy DNAs via in-situ generation of ROS and high temperature can be a very effective strategy to address this bottleneck. Recently, some emerging nucleus-targeting phototherapy nanodrugs have demonstrated extremely effective anticancer effects. However, reviews in the field are still rarely reported. Here, we comprehensively summarized recent advances in nucleus-targeting phototherapy in recent years. We classified nucleus-targeting phototherapy into three categories based on the characteristics of these nucleus-targeting strategies. The first category is the passive targeting strategy, which mainly targets the nucleus by adjusting the physicochemical characteristics of phototherapy nanomedicines. The second category is to mediate the phototherapy nanodrugs into the nucleus by modifying functional groups that actively target the nucleus. The third category is to assist nanodrugs enter into the nucleus in a light-controlled way. Finally, we provided our insights and prospects for nucleus-targeting phototherapy nanodrugs. This minireview provides unique insights and valuable clues in the design of phototherapy nanodrugs and other nucleus-targeting drugs.

Telerehabilitation-Based Physical Therapy Practice in the Philippines: Knowledge, Perceptions, Barriers, and Risks

Aim: The study aimed to determine the level of knowledge, perception, perceived barriers, and risks of telerehabilitation among Filipino Physical Therapists during the COVID-19 pandemic. Method: A descriptive, cross-sectional survey on the knowledge, perception, barriers, and risk to telerehabilitation-based Physical Therapy practice was conducted among Filipino Physical Therapists. The electronic survey questionnaire includes demographic profile, knowledge towards telerehabilitation, perceived barriers and risk, and overall perception of telerehabilitation practice during the COVID-19 pandemic. Descriptive statistics were used to summarize the responses. Results: A total of 55 respondents participated in the study. Results showed that most respondents (43; 78.2%) considered telerehabilitation a viable option to deliver rehabilitation services to patients during the COVID-19 pandemic. Furthermore, 62% (34) reported that they have a good knowledge of telerehabilitation. The main barriers that led to their limited use of telerehabilitation systems are lack of Information &amp; Communication Technology knowledge, its high cost, rapid changes, and patient compliance (31; 56.4%). In addition, patient data security, privacy, consultation from an unauthorized person, and difficulty establishing meaningful interactions with the patient were identified as risks associated with telerehabilitation (42; 76.4%). Conclusion and Implications: The use of telerehabilitation in the midst of the pandemic COVID-19 was well recognized and widely accepted by Filipino Physical Therapists; however, barriers and potential threats need to be minimized. Establishing telerehabilitation guidelines and increasing awareness will allow better delivery of telerehabilitation services. This study is vital in the provision of rehabilitation services to patients and the advancement of the profession in this time of public health crisis.

Oral Dissolving Films: A Comprehensive Review on Recent Perspectives and Current Approach to Effective Drug Delivery

Oral dissolving films are advanced oral dosage forms implied for the attachment onto the buccal mucosa and have both local and systemic effects. These dosage forms may be favored over other oral drug delivery systems in terms of flexibility and comfort. These films utilize the property of bioadhesion of certain polymers, which on hydration target a particular region of the body for extended period of time thereby bypassing first pass metabolism and promoting increased bioavailability. These films are self-administrable, pharmacoeconomic and have good patient compliance. Various techniques may be used for the formulation of oral dissolving films, among which solvent casting method is the most preferable. Usually hydrophilic polymers along with other excipients are used to formulate buccal films, which disintegrate quickly releasing the incorporated APIs within seconds. Oral dissolving films offer numerous benefits as far as accessibility, administration and withdrawal, retentivity, low enzymatic movement, economy and high patient compliance is concerned, thus having the potential for market and business exploitation. This preset review emphasizes on mechanism of action, merits, composition, formulation, evaluation, marketed formulations of oral dissolving films. Additionally, covering the aspects related to novel fast dissolving techniques.&#x0D; Keywords: Solvent casting method, buccal films, bioadhesion, hydration, bioavailability.

MCardia: A Context-Aware ECG Collection System for Ambulatory Arrhythmia Screening

This article presents the design, technical implementation, and feasibility evaluation of mCardia —a context-aware, mobile electrocardiogram (ECG) collection system for longitudinal arrhythmia screening under free-living conditions. Along with ECG, mCardia also records active and passive contextual data, including patient-reported symptoms and physical activity. This contextual data can provide a more accurate understanding of what happens before, during, and after an arrhythmia event, thereby providing additional information in the diagnosis of arrhythmia. By using a plugin-based architecture for ECG and contextual sensing, mCardia is device-agnostic and can integrate with various wireless ECG devices and supports cross-platform deployment. We deployed the mCardia system in a feasibility study involving 24 patients who used the system over a two-week period. During the study, we observed high patient acceptance and compliance with a satisfactory yield of collected ECG and contextual data. The results demonstrate the high usability and feasibility of mCardia for longitudinal ambulatory monitoring under free-living conditions. The article also reports from two clinical cases, which demonstrate how a cardiologist can utilize the collected contextual data to improve the accuracy of arrhythmia analysis. Finally, the article discusses the lessons learned and the challenges found in the mCardia design and the feasibility study.

Exploring Therapeutic Potential of Invasomes, Transfersomes, Transethosomes, Oleic Acid Vesicles, and Cubosomes Adopting Topical/Transdermal Route

Background: Transdermal drug delivery is considered a better alternative to oral administration of drugs like proteins or peptides that are susceptible to extensive degradation via first pass metabolism. This delivery route also shows high patient compliance due to no use of painful injections. Conventional delivery systems like creams and gel show poor skin permeation and high dosing frequency. Objective: The objective of this work was to investigate the role of highly advanced micro and nanocarrier systems like invasomes, transfersomes, transethosomes, oleic acid vesicles, and cubosomes for transdermal drug delivery exploring literature survey. Methods: Literature survey for these advanced micro and nanocarrier systems was carried out using search engines like Pubmed and Google scholar. Results: Results of literature investigations revealed that advanced micro and nanocarrier systems discussed earlier have the caliber to enhance skin permeation of various bioactives, show sustain release, and target particular areas of skin better compared to old nanocarriers like liposomes. Conclusion: The present review concludes that advanced micro and nanocarrier systems like invasomes, transfersomes, transethosomes, oleic acid vesicles, and cubosomes are better alternatives for transdermal delivery of therapeutic agents compared to old nanocarriers like liposomes and conventional delivery systems like creams and gels.

Advances in oral peptide drug nanoparticles for diabetes mellitus treatment.

Peptide drugs play an important role in diabetes mellitus treatment. Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration routes. However, there are a series of formidable unfavorable conditions present in the gastrointestinal (GI) tract after oral administration, which result in the low oral bioavailability of these peptide drugs. To overcome these challenges, various nanoparticles (NPs) have been developed to improve the oral absorption of peptide drugs due to their unique in vivo properties and high design flexibility. This review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these challenges. The review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus treatment. Finally, we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug NPs. Our aim is to provide a systemic and comprehensive review of oral peptide drug NPs that can overcome the challenges in GI tract for efficient treatment of diabetes mellitus.

Self-propelled Janus micromotors for pH-responsive release of small molecule drug

Oral administration of drugs has received significant attention in the last 1, 2 decades, as it is the most comfortable and painless administration route, which leads to high patient compliance. Although oral delivery of drugs shows positive effects in patients, several hurdles must be overcome such as enzymatic degradation, large pH-variations found throughout the gastrointestinal (GI) tract, and continuous mucus secretion. We have studied biocompatible non-toxic micromotors as promising man-made microdevices for targeted furosemide release. Micromotors are micro-scale autonomous entities that can perform various tasks in the GI tract as a result of their impressive motion abilities. Their directional motion makes them ideal candidates to bring the necessary drug dosage to where it is needed. Herein, the micromotors were loaded for the first time with furosemide and coated with pH-sensitive polymer Eudragit® L100 using ultrasonic spray coating technique in order to achieve targeted drug delivery and pH-responsive release. Coherent anti-Stokes Raman scattering spectroscopy (CARS) was used for visualizing drug loading efficiency on the surface of micromotors. In vitro drug release was evaluated under acidic and neutral pH chemical environments and obtained results confirm their function as pH-sensitive microdevices for a drug release.

Acupuncture combined with traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for chronic insomnia: study protocol for a randomized controlled trial

IntroductionThe incidence of insomnia is getting higher and higher. Long-term insomnia seriously affects people’s health. Drug use is usually accompanied with adverse events. Both acupuncture and cognitive behavioral therapy for insomnia (CBT-I) have been proven to be safe and effective non-pharmacological treatments for insomnia. As the insomniacs’ bad sleep behavior and wrong cognition have not been effectively corrected, acupuncture has a quick effect, high patient compliance but unstable long-term efficacy, while CBT-I is complex, time-consuming, and expensive; additionally, patient compliance is low, and the number of trained therapists is limited, making it difficult to carry out. Therefore, this study aims to use the insomnia TCM system to construct a convenient and feasible traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for Chinese people, and combine the advantages of acupuncture and TCM-eCBT-I for maintaining long-term efficacy, and three treatments will be evaluated to provide clinicians with a more effective clinical protocolMethods and analysisThis study is a single-center, open-label, randomized controlled trial. Ninety subjects will be recruited and randomly assigned to three groups: the acupuncture group, the TCM-eCBT-I group, and the acupuncture combined with TCM-eCBT-I group, in a ratio of 1:1:1. We will evaluate the Pittsburgh Sleep Quality Index (PSQI) and Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS), Insomnia Severity Index (ISI), sleep diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 Scale (FS-14) scales. All adverse reactions will be assessed through the ADVERSE event table. All outcomes will be evaluated online at 0 weeks, 4 weeks, 8 weeks, 16 weeks, and 28weeks.Ethics and disseminationThis study has been approved by the Institutional Review Board of the Affiliated Hospital of Nanjing University of Chinese Medicine (2020 NL-018-02). Informed consent will be obtained from all the subjects. The results will be shared with sleep researchers, public, and relevant academic institutions through high-impact peer-reviewed publications.Trial registrationChinese Clinical Trial Registry ChiCTR2000032960. Registered on 17 May 2020