TY - JOUR AU - Ji, Huanhuan AU - Gong, Meiling AU - Gong, Li AU - Zhang, Ni AU - Zhou, Ruiou AU - Deng, Dongmei AU - Yang, Ya AU - Song, Lin AU - Jia, Yuntao PY - 2025/3/25 TI - Detection of Clinically Significant Drug-Drug Interactions in Fatal Torsades de Pointes: Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System JO - J Med Internet Res SP - e65872 VL - 27 KW - torsades de pointes KW - FAERS database KW - drug-drug interactions KW - QTc-prolonging drugs KW - adverse drug events N2 - Background: Torsades de pointes (TdP) is a rare yet potentially fatal cardiac arrhythmia that is often drug-induced. Drug-drug interactions (DDIs) are a major risk factor for TdP development, but the specific drug combinations that increase this risk have not been extensively studied. Objective: This study aims to identify clinically significant, high-priority DDIs to provide a foundation to minimize the risk of TdP and effectively manage DDI risks in the future. Methods: We used the following 4 frequency statistical models to detect DDI signals using the Food and Drug Administration Adverse Event Reporting System (FAERS) database: ? shrinkage measure, combination risk ratio, chi-square statistic, and additive model. The adverse event of interest was TdP, and the drugs targeted were all registered and classified as ?suspect,? ?interacting,? or ?concomitant drugs? in FAERS. The DDI signals were identified and evaluated using the Lexicomp and Drugs.com databases, supplemented with real-world data from the literature. Results: As of September 2023, this study included 4313 TdP cases, with 721 drugs and 4230 drug combinations that were reported for at least 3 cases. The ? shrinkage measure model demonstrated the most conservative signal detection, whereas the chi-square statistic model exhibited the closest similarity in signal detection tendency to the ? shrinkage measure model. The ? value was 0.972 (95% CI 0.942-1.002), and the Ppositive and Pnegative values were 0.987 and 0.985, respectively. We detected 2158 combinations using the 4 frequency statistical models, of which 241 combinations were indexed by Drugs.com or Lexicomp and 105 were indexed by both. The most commonly interacting drugs were amiodarone, citalopram, quetiapine, ondansetron, ciprofloxacin, methadone, escitalopram, sotalol, and voriconazole. The most common combinations were citalopram and quetiapine, amiodarone and ciprofloxacin, amiodarone and escitalopram, amiodarone and fluoxetine, ciprofloxacin and sotalol, and amiodarone and citalopram. Although 38 DDIs were indexed by Drugs.com and Lexicomp, they were not detected by any of the 4 models. Conclusions: Clinical evidence on DDIs is limited, and not all combinations of heart rate?corrected QT interval (QTc)?prolonging drugs result in TdP, even when involving high-risk drugs or those with known risk of TdP. This study provides a comprehensive real-world overview of drug-induced TdP, delimiting both clinically significant DDIs and negative DDIs, providing valuable insights into the safety profiles of various drugs, and informing the optimization of clinical practice. UR - https://www.jmir.org/2025/1/e65872 UR - http://dx.doi.org/10.2196/65872 UR - http://www.ncbi.nlm.nih.gov/pubmed/ ID - info:doi/10.2196/65872 ER - TY - JOUR AU - Gong, Chan-Juan AU - Zhou, Xiao-Kai AU - Zhang, Zhen-Feng AU - Fang, Yin PY - 2025/1/13 TI - Impact of Preventive Intravenous Amiodarone on Reperfusion Ventricular Fibrillation in Patients With Left Ventricular Hypertrophy Undergoing Open-Heart Surgery: Randomized Controlled Clinical Trial JO - JMIR Form Res SP - e64586 VL - 9 KW - amiodarone KW - left ventricular hypertrophy KW - reperfusion ventricular fibrillation KW - open-heart surgery KW - randomized controlled trial KW - RCT KW - clinical trial KW - ventricular fibrillation KW - vicious arrhythmia KW - aortic cross-clamp KW - surgery KW - effectiveness KW - defibrillation N2 - Background: Ventricular fibrillation (VF) is a vicious arrhythmia usually generated after removal of the aortic cross-clamp (ACC) in patients undergoing open-heart surgery, which could damage cardiomyocytes, especially in patients with left ventricular hypertrophy (LVH). Amiodarone has the prominent properties of converting VF and restoring sinus rhythm. However, few studies concentrated on the effect of amiodarone before ACC release on reducing VF in patients with LVH. Objective: The study was designed to explore the effectiveness of prophylactic intravenous amiodarone in reducing VF after the release of the ACC in patients with LVH. Methods: A total of 54 patients with LVH scheduled for open-heart surgery were enrolled and randomly divided (1:1) into 2 groups?group A (amiodarone group) and group P (placebo-controlled group). Thirty minutes before removal of the ACC, the trial drugs were administered intravenously. In group A, 150 mg of amiodarone was pumped in 15 minutes. In group P, the same volume of normal saline was pumped in 15 minutes. The primary outcome was the incidence of VF 10 minutes after removal of the ACC. Results: The incidence of VF was lower in group A than in group P (30% vs 70%, P=.003). The duration of VF, the number of defibrillations, and the defibrillation energy were also lower in group A than in group P (P<.001, P=.002, and P=.002, respectively). After the end of cardiopulmonary bypass, the heart rate and mean arterial pressure were lower in group A, and the mean pulmonary arterial pressure and the dose of vasoactive drugs were higher than those in group P (P<.001, P<.001, P=.04, and P=.02, respectively). However, there were no significant differences in the use of vasoactive-inotropic agents and hemodynamic status between the 2 groups before the end of surgery. Conclusions: In patients with LVH who undergo open-heart surgery, amiodarone can be safely used to reduce the incidence of VF, the duration of VF, the frequency of defibrillation, and the energy of defibrillation after ACC removal. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000035057; https://www.chictr.org.cn/showprojEN.html?proj=57145 UR - https://formative.jmir.org/2025/1/e64586 UR - http://dx.doi.org/10.2196/64586 ID - info:doi/10.2196/64586 ER - TY - JOUR AU - Helgeson, A. Scott AU - Mudgalkar, M. Rohan AU - Jacobs, A. Keith AU - Lee, S. Augustine AU - Sanghavi, Devang AU - Moreno Franco, Pablo AU - Brooks, S. Ian AU - PY - 2024/11/18 TI - Association Between X/Twitter and Prescribing Behavior During the COVID-19 Pandemic: Retrospective Ecological Study JO - JMIR Infodemiology SP - e56675 VL - 4 KW - social media KW - infodemic KW - COVID-19 KW - healthcare utilization KW - misinformation KW - disinformation KW - Twitter KW - hydroxychloroquine KW - X KW - drugs KW - pharmacy KW - pharmacology KW - pharmacotherapy KW - pharmaceuticals KW - medication KW - prescription KW - sentiment KW - SARS-CoV-2 KW - pandemic KW - respiratory KW - infectious N2 - Background: Social media has become a vital tool for health care providers to quickly share information. However, its lack of content curation and expertise poses risks of misinformation and premature dissemination of unvalidated data, potentially leading to widespread harmful effects due to the rapid and large-scale spread of incorrect information. Objective: We aim to determine whether social media had an undue association with the prescribing behavior of hydroxychloroquine, using the COVID-19 pandemic as the setting. Methods: In this retrospective study, we gathered the use of hydroxychloroquine in 48 hospitals in the United States between January and December 2020. Social media data from X/Twitter was collected using Brandwatch, a commercial aggregator with access to X/Twitter?s data, and focused on mentions of ?hydroxychloroquine? and ?Plaquenil.? Tweets were categorized by sentiment (positive, negative, or neutral) using Brandwatch?s sentiment analysis tool, with results classified by date. Hydroxychloroquine prescription data from the National COVID Cohort Collaborative for 2020 was used. Granger causality and linear regression models were used to examine relationships between X/Twitter mentions and prescription trends, using optimum time lags determined via vector auto-regression. Results: A total of 581,748 patients with confirmed COVID-19 were identified. The median daily number of positive COVID-19 cases was 1318.5 (IQR 1005.75-1940.3). Before the first confirmed COVID-19 case, hydroxychloroquine was prescribed at a median rate of 559 (IQR 339.25-728.25) new prescriptions per day. A day-of-the-week effect was noted in both prescriptions and case counts. During the pandemic in 2020, hydroxychloroquine prescriptions increased significantly, with a median of 685.5 (IQR 459.75-897.25) per day, representing a 22.6% rise from baseline. The peak occurred on April 2, 2020, with 3411 prescriptions, a 397.6% increase. Hydroxychloroquine mentions on X/Twitter peaked at 254,770 per day on April 5, 2020, compared to a baseline of 9124 mentions per day before January 21, 2020. During this study?s period, 3,823,595 total tweets were recorded, with 10.09% (n=386,115) positive, 37.87% (n=1,448,030) negative, and 52.03% (n=1,989,450) neutral sentiments. A 1-day lag was identified as the optimal time for causal association between tweets and hydroxychloroquine prescriptions. Univariate analysis showed significant associations across all sentiment types, with the largest impact from positive tweets. Multivariate analysis revealed only neutral and negative tweets significantly affected next-day prescription rates. Conclusions: During the first year of the COVID-19 pandemic, there was a significant association between X/Twitter mentions and the number of prescriptions of hydroxychloroquine. This study showed that X/Twitter has an association with the prescribing behavior of hydroxychloroquine. Clinicians need to be vigilant about their potential unconscious exposure to social media as a source of medical knowledge, and health systems and organizations need to be more diligent in identifying expertise, source, and quality of evidence when shared on social media platforms. UR - https://infodemiology.jmir.org/2024/1/e56675 UR - http://dx.doi.org/10.2196/56675 UR - http://www.ncbi.nlm.nih.gov/pubmed/39556417 ID - info:doi/10.2196/56675 ER - TY - JOUR AU - Ashraf, Reza Amir AU - Mackey, Ken Tim AU - Vida, György Róbert AU - Kulcsár, Gy?z? AU - Schmidt, János AU - Balázs, Orsolya AU - Domián, Márk Bálint AU - Li, Jiawei AU - Csákó, Ibolya AU - Fittler, András PY - 2024/11/7 TI - Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription: Market Surveillance, Content Analysis, and Product Purchase Evaluation Study JO - J Med Internet Res SP - e65440 VL - 26 KW - semaglutide KW - Ozempic KW - Wegovy KW - search engines KW - online pharmacies KW - patient safety KW - medication safety KW - nondelivery schemes KW - counterfeit KW - substandard and falsified medical products N2 - Background: Over the past 4 decades, obesity has escalated into a global epidemic, with its worldwide prevalence nearly tripling. Pharmacological treatments have evolved with the recent development of glucagon-like peptide 1 agonists, such as semaglutide. However, off-label use of drugs such as Ozempic for cosmetic weight loss has surged in popularity, raising concerns about potential misuse and the emergence of substandard and falsified products in the unregulated supply chain. Objective: This study aims to conduct a multifactor investigation of product quality and patient safety risks associated with the unregulated online sale of semaglutide by examining product availability and vendor characteristics and assessing product quality through test purchases. Methods: We used a complex risk and quality assessment methodology combining online market surveillance, search engine results page analysis, website content assessment, domain traffic analytics, conducting targeted product test purchases, visual quality inspection of product packaging, microbiological sterility and endotoxin contamination evaluation, and quantitative sample analysis using liquid chromatography coupled with mass spectrometry. Results: We collected and evaluated 1080 links from search engine results pages and identified 317 (29.35%) links belonging to online pharmacies, of which 183 (57.7%) led to legal pharmacies and 134 (42.3%) directed users to 59 unique illegal online pharmacy websites. Web traffic data for the period between July and September 2023 revealed that the top 30 domains directly or indirectly affiliated with illegal online pharmacies accumulated over 4.7 million visits. Test purchases were completed from 6 illegal online pharmacies with the highest number of links offering semaglutide products for sale without prescription at the lowest price range. Three injection vial purchases were delivered; none of the 3 Ozempic prefilled injection pens were received due to nondelivery e-commerce scams. All purchased vials were considered probable substandard and falsified products, as visual inspection indicated noncompliance in more than half (59%-63%) of the evaluated criteria. The semaglutide content of samples substantially exceeded labeled amounts by 28.56%-38.69%, although no peptide-like impurities were identified. The lyophilized peptide samples were devoid of viable microorganisms at the time of testing; however, endotoxin was detected in all samples with levels ranging between 2.1645 EU/mg and 8.9511 EU/mg. Furthermore, the measured semaglutide purity was significantly low, ranging between 7.7% and 14.37% and deviating from the 99% claimed on product labels by manufacturers. Conclusions: Glucagon-like peptide 1 agonist drugs promoted for weight loss, similar to erectile dysfunction medications more than 2 decades ago, are becoming the new blockbuster lifestyle medications for the illegal online pharmacy market. Protecting the pharmaceutical supply chain from substandard and falsified weight loss products and raising awareness regarding online medication safety must be a public health priority for regulators and technology platforms alike. UR - https://www.jmir.org/2024/1/e65440 UR - http://dx.doi.org/10.2196/65440 UR - http://www.ncbi.nlm.nih.gov/pubmed/ ID - info:doi/10.2196/65440 ER - TY - JOUR AU - Romano, D. Joseph AU - Truong, Van AU - Kumar, Rachit AU - Venkatesan, Mythreye AU - Graham, E. Britney AU - Hao, Yun AU - Matsumoto, Nick AU - Li, Xi AU - Wang, Zhiping AU - Ritchie, D. Marylyn AU - Shen, Li AU - Moore, H. Jason PY - 2024/4/18 TI - The Alzheimer?s Knowledge Base: A Knowledge Graph for Alzheimer Disease Research JO - J Med Internet Res SP - e46777 VL - 26 KW - Alzheimer disease KW - knowledge graph KW - knowledge base KW - artificial intelligence KW - drug repurposing KW - drug discovery KW - open source KW - Alzheimer KW - etiology KW - heterogeneous graph KW - therapeutic targets KW - machine learning KW - therapeutic discovery N2 - Background: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease?s etiology and response to drugs. Objective: We designed the Alzheimer?s Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. Methods: We designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. Results: AlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. Conclusions: AlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge. UR - https://www.jmir.org/2024/1/e46777 UR - http://dx.doi.org/10.2196/46777 UR - http://www.ncbi.nlm.nih.gov/pubmed/38635981 ID - info:doi/10.2196/46777 ER - TY - JOUR AU - Kitahiro, Yumi AU - Yamamoto, Kazuhiro AU - Yakushijin, Kimikazu AU - Ioroi, Takeshi AU - Tanda, Masaaki AU - Itohara, Kotaro AU - Omura, Tomohiro AU - Minami, Hironobu AU - Yano, Ikuko PY - 2024/2/22 TI - The Efficacy of Bepotastine Besilate Compared With Hydroxyzine Pamoate for Preventing Infusion Reactions to the First Dose of Rituximab in Patients With Non-Hodgkin Lymphoma: Protocol for a Phase II, Double-Blind, Multicenter Randomized Trial JO - JMIR Res Protoc SP - e54882 VL - 13 KW - non-Hodgkin lymphoma KW - rituximab KW - infusion reactions KW - bepotastine besilate KW - histamine H1-receptor antagonist KW - hydroxyzine pamoate KW - drowsiness N2 - Background: Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. Objective: This study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. Methods: This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist?induced drowsiness using the visual analogue scale, with each patient providing their individual response. Results: This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. Conclusions: This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. Trial Registration: Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169 International Registered Report Identifier (IRRID): DERR1-10.2196/54882 UR - https://www.researchprotocols.org/2024/1/e54882 UR - http://dx.doi.org/10.2196/54882 UR - http://www.ncbi.nlm.nih.gov/pubmed/38386393 ID - info:doi/10.2196/54882 ER - TY - JOUR AU - Smith, Patrice Brandi AU - Hoots, Brooke AU - DePadilla, Lara AU - Roehler, R. Douglas AU - Holland, M. Kristin AU - Bowen, A. Daniel AU - Sumner, A. Steven PY - 2023/12/21 TI - Using Transformer-Based Topic Modeling to Examine Discussions of Delta-8 Tetrahydrocannabinol: Content Analysis JO - J Med Internet Res SP - e49469 VL - 25 KW - social media KW - natural language processing KW - public health surveillance KW - machine learning KW - topic modeling KW - delta-8 tetrahydrocannabinol KW - cannabis KW - marijuana N2 - Background: Delta-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid found in small amounts naturally in the cannabis plant; it can also be synthetically produced in larger quantities from hemp-derived cannabidiol. Most states permit the sale of hemp and hemp-derived cannabidiol products; thus, hemp-derived delta-8 THC products have become widely available in many state hemp marketplaces, even where delta-9 THC, the most prominently occurring THC isomer in cannabis, is not currently legal. Health concerns related to the processing of delta-8 THC products and their psychoactive effects remain understudied. Objective: The goal of this study is to implement a novel topic modeling approach based on transformers, a state-of-the-art natural language processing architecture, to identify and describe emerging trends and topics of discussion about delta-8 THC from social media discourse, including potential symptoms and adverse health outcomes experienced by people using delta-8 THC products. Methods: Posts from January 2008 to December 2021 discussing delta-8 THC were isolated from cannabis-related drug forums on Reddit (Reddit Inc), a social media platform that hosts the largest web-based drug forums worldwide. Unsupervised topic modeling with state-of-the-art transformer-based models was used to cluster posts into topics and assign labels describing the kinds of issues being discussed with respect to delta-8 THC. Results were then validated by human subject matter experts. Results: There were 41,191 delta-8 THC posts identified and 81 topics isolated, the most prevalent being (1) discussion of specific brands or products, (2) comparison of delta-8 THC to other hemp-derived cannabinoids, and (3) safety warnings. About 5% (n=1220) of posts from the resulting topics included content discussing health-related symptoms such as anxiety, sleep disturbance, and breathing problems. Until 2020, Reddit posts contained fewer than 10 mentions of delta-8-THC for every 100,000 cannabis posts annually. However, in 2020, these rates increased by 13 times the 2019 rate (to 99.2 mentions per 100,000 cannabis posts) and continued to increase into 2021 (349.5 mentions per 100,000 cannabis posts). Conclusions: Our study provides insights into emerging public health concerns around delta-8 THC, a novel substance about which little is known. Furthermore, we demonstrate the use of transformer-based unsupervised learning approaches to derive intelligible topics from highly unstructured discussions of delta-8 THC, which may help improve the timeliness of identification of emerging health concerns related to new substances. UR - https://www.jmir.org/2023/1/e49469 UR - http://dx.doi.org/10.2196/49469 UR - http://www.ncbi.nlm.nih.gov/pubmed/38127427 ID - info:doi/10.2196/49469 ER - TY - JOUR AU - Rodríguez-Molinero, Alejandro AU - Pérez-López, Carlos AU - Salazar González, L. Jose AU - Garcia-Lerma, Esther AU - Álvarez-García, A. Juan AU - Soria Morillo, M. Luis AU - Salas Fernández, Tomás PY - 2023/11/14 TI - Drug Repurposing for Cancers With Limited Survival: Protocol for a Retrospective Cohort Study JO - JMIR Res Protoc SP - e48925 VL - 12 KW - cancer KW - death KW - drug repurposing KW - epidemiology KW - mortality KW - oncology KW - pharmacoepidemiology KW - pharmacology KW - side effects KW - survival KW - survivors N2 - Background: Only 5% of the molecules tested in oncology phase 1 trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of dollars. To reduce the cost and shorten the time of discovery of new treatments, ?drug repurposing? (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies. Objective: The objective of this study is to identify drugs currently marketed for other indications that may have an effect on the prognosis of patients with cancer. Methods: We plan to monitor a cohort of patients with high-lethality cancers treated in the public health system of Catalonia between 2006 and 2012, retrospectively, for survival for 5 years after diagnosis or until death. A control cohort, comprising people without cancer, will also be retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of cancer (patients with cancer cohort), date and cause of death, pharmacological treatment, sex, age, and place of residence. During the first stage of statistical analysis of the patients with cancer cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In the second stage, the survival associated with the consumption of each relevant drug will be analyzed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with cancer or whether they also occur in patients without cancer. Results: We anticipate discovering multiple significant associations between commonly used drugs and the survival outcomes of patients with cancer. We expect to publish the initial results in the first half of 2024. Conclusions: This retrospective study may identify several commonly used drugs as candidates for repurposing in the treatment of various cancers. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials. However, the results of this study may accelerate drug discovery in oncology. International Registered Report Identifier (IRRID): DERR1-10.2196/48925 UR - https://www.researchprotocols.org/2023/1/e48925 UR - http://dx.doi.org/10.2196/48925 UR - http://www.ncbi.nlm.nih.gov/pubmed/37962929 ID - info:doi/10.2196/48925 ER - TY - JOUR AU - Estarreja, Joăo AU - Mendes, Priscila AU - Silva, Carina AU - Camacho, Pedro AU - Mateus, Vanessa PY - 2023/6/9 TI - The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis JO - JMIR Res Protoc SP - e38658 VL - 12 KW - wet macular degeneration KW - age-related macular degeneration KW - AMD KW - neovascular age-related macular degeneration KW - nAMD KW - bevacizumab KW - drug therapy N2 - Background: Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti?vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. Objective: This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. Methods: This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. Conclusions: This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD. Trial Registration: PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk International Registered Report Identifier (IRRID): DERR1-10.2196/38658 UR - https://www.researchprotocols.org/2023/1/e38658 UR - http://dx.doi.org/10.2196/38658 UR - http://www.ncbi.nlm.nih.gov/pubmed/37294608 ID - info:doi/10.2196/38658 ER - TY - JOUR AU - Kochuthakidiyel Suresh, Praveenkumar AU - Sekar, Gnanasoundari AU - Mallady, Kavya AU - Wan Ab Rahman, Suriana Wan AU - Shima Shahidan, Nazatul Wan AU - Venkatesan, Gokulakannan PY - 2023/5/9 TI - The Identification of Potential Drugs for Dengue Hemorrhagic Fever: Network-Based Drug Reprofiling Study JO - JMIR Bioinform Biotech SP - e37306 VL - 4 KW - dengue hemorrhagic fever KW - drug reprofiling KW - network pharmacology KW - network medicine KW - DHF KW - repurposable drugs KW - viral fevers KW - drug repurposing N2 - Background: Dengue fever can progress to dengue hemorrhagic fever (DHF), a more serious and occasionally fatal form of the disease. Indicators of serious disease arise about the time the fever begins to reduce (typically 3 to 7 days following symptom onset). There are currently no effective antivirals available. Drug repurposing is an emerging drug discovery process for rapidly developing effective DHF therapies. Through network pharmacology modeling, several US Food and Drug Administration (FDA)-approved medications have already been researched for various viral outbreaks. Objective: We aimed to identify potentially repurposable drugs for DHF among existing FDA-approved drugs for viral attacks, symptoms of viral fevers, and DHF. Methods: Using target identification databases (GeneCards and DrugBank), we identified human?DHF virus interacting genes and drug targets against these genes. We determined hub genes and potential drugs with a network-based analysis. We performed functional enrichment and network analyses to identify pathways, protein-protein interactions, tissues where the gene expression was high, and disease-gene associations. Results: Analyzing virus-host interactions and therapeutic targets in the human genome network revealed 45 repurposable medicines. Hub network analysis of host-virus-drug associations suggested that aspirin, captopril, and rilonacept might efficiently treat DHF. Gene enrichment analysis supported these findings. According to a Mayo Clinic report, using aspirin in the treatment of dengue fever may increase the risk of bleeding complications, but several studies from around the world suggest that thrombosis is associated with DHF. The human interactome contains the genes prostaglandin-endoperoxide synthase 2 (PTGS2), angiotensin converting enzyme (ACE), and coagulation factor II, thrombin (F2), which have been documented to have a role in the pathogenesis of disease progression in DHF, and our analysis of most of the drugs targeting these genes showed that the hub gene module (human-virus-drug) was highly enriched in tissues associated with the immune system (P=7.29 × 10?24) and human umbilical vein endothelial cells (P=1.83 × 10?20); this group of tissues acts as an anticoagulant barrier between the vessel walls and blood. Kegg analysis showed an association with genes linked to cancer (P=1.13 × 10?14) and the advanced glycation end products?receptor for advanced glycation end products signaling pathway in diabetic complications (P=3.52 × 10?14), which indicates that DHF patients with diabetes and cancer are at risk of higher pathogenicity. Thus, gene-targeting medications may play a significant part in limiting or worsening the condition of DHF patients. Conclusions: Aspirin is not usually prescribed for dengue fever because of bleeding complications, but it has been reported that using aspirin in lower doses is beneficial in the management of diseases with thrombosis. Drug repurposing is an emerging field in which clinical validation and dosage identification are required before the drug is prescribed. Further retrospective and collaborative international trials are essential for understanding the pathogenesis of this condition. UR - https://bioinform.jmir.org/2023/1/e37306 UR - http://dx.doi.org/10.2196/37306 UR - http://www.ncbi.nlm.nih.gov/pubmed/ ID - info:doi/10.2196/37306 ER - TY - JOUR AU - Koss, Jonathan AU - Bohnet-Joschko, Sabine PY - 2022/10/3 TI - Social Media Mining of Long-COVID Self-Medication Reported by Reddit Users: Feasibility Study to Support Drug Repurposing JO - JMIR Form Res SP - e39582 VL - 6 IS - 10 KW - social media mining KW - drug repurposing KW - long-COVID KW - crowdsourcing KW - COVID-19 KW - Reddit KW - social media KW - content analysis KW - network analysis KW - recognition algorithm KW - treatment N2 - Background: Since the beginning of the COVID-19 pandemic, over 480 million people have been infected and more than 6 million people have died from COVID-19 worldwide. In some patients with acute COVID-19, symptoms manifest over a longer period, which is also called ?long-COVID.? Unmet medical needs related to long-COVID are high, since there are no treatments approved. Patients experiment with various medications and supplements hoping to alleviate their suffering. They often share their experiences on social media. Objective: The aim of this study was to explore the feasibility of social media mining methods to extract important compounds from the perspective of patients. The goal is to provide an overview of different medication strategies and important agents mentioned in Reddit users? self-reports to support hypothesis generation for drug repurposing, by incorporating patients? experiences. Methods: We used named-entity recognition to extract substances representing medications or supplements used to treat long-COVID from almost 70,000 posts on the ?/r/covidlonghaulers? subreddit. We analyzed substances by frequency, co-occurrences, and network analysis to identify important substances and substance clusters. Results: The named-entity recognition algorithm achieved an F1 score of 0.67. A total of 28,447 substance entities and 5789 word co-occurrence pairs were extracted. ?Histamine antagonists,? ?famotidine,? ?magnesium,? ?vitamins,? and ?steroids? were the most frequently mentioned substances. Network analysis revealed three clusters of substances, indicating certain medication patterns. Conclusions: This feasibility study indicates that network analysis can be used to characterize the medication strategies discussed in social media. Comparison with existing literature shows that this approach identifies substances that are promising candidates for drug repurposing, such as antihistamines, steroids, or antidepressants. In the context of a pandemic, the proposed method could be used to support drug repurposing hypothesis development by prioritizing substances that are important to users. UR - https://formative.jmir.org/2022/10/e39582 UR - http://dx.doi.org/10.2196/39582 UR - http://www.ncbi.nlm.nih.gov/pubmed/36007131 ID - info:doi/10.2196/39582 ER - TY - JOUR AU - Ozawa, Sachiko AU - Billings, Joanna AU - Sun, Yujiao AU - Yu, Sushan AU - Penley, Benjamin PY - 2022/2/16 TI - COVID-19 Treatments Sold Online Without Prescription Requirements in the United States: Cross-sectional Study Evaluating Availability, Safety and Marketing of Medications JO - J Med Internet Res SP - e27704 VL - 24 IS - 2 KW - COVID-19 KW - medication KW - internet KW - online pharmacy KW - drug N2 - Background: The COVID-19 pandemic has increased online purchases and heightened interest in existing treatments. Dexamethasone, hydroxychloroquine, and lopinavir-ritonavir have been touted as potential COVID-19 treatments. Objective: This study assessed the availability of 3 potential COVID-19 treatments online and evaluated the safety and marketing characteristics of websites selling these products during the pandemic. Methods: A cross-sectional study was conducted in the months of June 2020 to August 2020, by searching the first 100 results on Google, Bing, and Yahoo! mimicking a US consumer. Unique websites were included if they sold targeted medicines, were in English, offered US shipping, and were free to access. Identified online pharmacies were categorized as rogue, unclassified, or legitimate based on LegitScript classifications. Patient safety characteristics, marketing techniques, price, legitimacy, IP addresses, and COVID-19 mentions were recorded. Results: We found 117 websites: 30 selling dexamethasone (19/30, 63% rogue), 39 selling hydroxychloroquine (22/39, 56% rogue), and 48 selling lopinavir-ritonavir (33/48, 69% rogue). This included 89 unique online pharmacies: 70% were rogue (n=62), 22% were unapproved (n=20), and 8% were considered legitimate (n=7). Prescriptions were not required among 100% (19/19), 61% (20/33), and 50% (11/22) of rogue websites selling dexamethasone, lopinavir-ritonavir, and hydroxychloroquine, respectively. Overall, only 32% (24/74) of rogue websites required prescriptions to buy these medications compared with 94% (31/33) of unapproved and 100% (10/10) of legitimate websites (P<.001). Rogue sites rarely offered pharmacist counseling (1/33, 3% for lopinavir-ritonavir to 2/22, 9% for hydroxychloroquine). Drug warnings were unavailable in 86% (6/7) of unapproved dexamethasone sites. It was difficult to distinguish between rogue, unapproved, and legitimate online pharmacies solely based on website marketing characteristics. Illegitimate pharmacies were more likely to offer bulk discounts and claim price discounts, yet dexamethasone and hydroxychloroquine were more expensive online. An inexpensive generic version of lopinavir-ritonavir that is not authorized for use in the United States was available online offering US shipping. Some websites claimed hydroxychloroquine and lopinavir-ritonavir were effective COVID-19 treatments despite lack of scientific evidence. In comparing IP addresses to locations claimed on the websites, only 8.5% (7/82) matched their claimed locations. Conclusions: The lack of safety measures by illegitimate online pharmacies endanger patients, facilitating access to medications without appropriate oversight by health care providers to monitor clinical response, drug interactions, and adverse effects. We demonstrated how easy it is to go online to buy medications that are touted to treat COVID-19 even when current clinical evidence does not support their use for self-treatment. We documented that illegitimate online pharmacies sidestep prescription requirements, skirt pharmacist counseling, and make false claims regarding efficacy for COVID-19 treatment. Health care professionals must urgently educate the public of the dangers of purchasing drugs from illegitimate websites and highlight the importance of seeking treatment through authentic avenues of care. UR - https://www.jmir.org/2022/2/e27704 UR - http://dx.doi.org/10.2196/27704 UR - http://www.ncbi.nlm.nih.gov/pubmed/34662286 ID - info:doi/10.2196/27704 ER - TY - JOUR AU - Shahzadi, Kiran Syeda AU - Karuvantevida, Noushad AU - Banerjee, Yajnavalka PY - 2021/12/21 TI - A Venomics Approach to the Identification and Characterization of Bioactive Peptides From Animal Venoms for Colorectal Cancer Therapy: Protocol for a Proof-of-Concept Study JO - JMIR Res Protoc SP - e31128 VL - 10 IS - 12 KW - animal venoms KW - colorectal cancer KW - bioactive peptides KW - high-throughput screening KW - venom KW - cancer KW - colorectal KW - peptide KW - screening KW - treatment KW - conceptual KW - characterize KW - development KW - therapy N2 - Background: Cancer is the third leading cause of death in the United Arab Emirates (UAE), after cardiovascular diseases and accidents. In the UAE, colorectal cancer (CRC) is the first and fourth most common cancer in males and females, respectively. Several treatment modalities have been employed for cancer treatment, such as surgery, radiotherapy, chemotherapy, hormone replacement therapy, and immunotherapy. These treatment modalities often elicit adverse effects on normal cells, causing toxic side effects. To circumvent these toxicities, there has been an increased impetus towards the identification of alternate treatment strategies. Animal venoms are rich sources of pharmacologically active polypeptides and proteins. Objective: In this proof-of-concept study, we will apply a high-throughput venomics strategy to identify and characterize anticancer bioactive peptides (BAPs) from 20 different animal venoms, specifically targeting CRC. We chose to focus on CRC because it is one of the foremost health issues in the UAE. Methods: In the initial study, we will screen 2500 different peptides derived from 20 different animal venoms for anticancer activity specifically directed against 3 CRC cell lines and two control cell lines employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay for cytotoxicity. Of the 20 venoms, 3 that exhibit specific and potent anticancer activity directed against the 3 CRC cell lines will be selected; and from these 3 venoms, the specific peptides with anti-CRC activity will be isolated and characterized. Results: This study is at the protocol development stage only, and as such, no results are available. However, we have initiated the groundwork required to disseminate the proposed study, which includes culturing of colorectal cancer cell lines and preparation of venom screens. Conclusions: In summary, the proposed study will generate therapeutic leads to manage and treat one of the leading health issues in the UAE, namely, CRC. International Registered Report Identifier (IRRID): PRR1-10.2196/31128 UR - https://www.researchprotocols.org/2021/12/e31128 UR - http://dx.doi.org/10.2196/31128 UR - http://www.ncbi.nlm.nih.gov/pubmed/34932002 ID - info:doi/10.2196/31128 ER - TY - JOUR AU - Borysowski, Jan AU - Górski, Andrzej PY - 2021/10/28 TI - ClinicalTrials.gov as a Source of Information About Expanded Access Programs: Cohort Study JO - J Med Internet Res SP - e26890 VL - 23 IS - 10 KW - ClinicalTrials.gov KW - expanded access KW - expanded access program KW - compassionate use KW - unapproved drug KW - investigational drug N2 - Background: ClinicalTrials.gov (CT.gov) is the most comprehensive internet-based register of different types of clinical studies. Expanded access is the use of unapproved drugs, biologics, or medical devices outside of clinical trials. One of the key problems in expanded access is the availability to both health care providers and patients of information about unapproved treatments. Objective: We aimed to evaluate CT.gov as a potential source of information about expanded access programs. Methods: We assessed the completeness of information in the records of 228 expanded access programs registered with CT.gov from February 2017 through May 2020. Moreover, we examined what percentage of published expanded access studies has been registered with CT.gov. Logistic regression (univariate and multivariate) and mediation analyses were used to identify the predictors of the absence of some information and a study?s nonregistration. Results: We found that some important data were missing from the records of many programs. Information that was missing most often included a detailed study description, facility information, central contact person, and eligibility criteria (55.3%, 54.0%, 41.7%, and 17.5% of the programs, respectively). Multivariate analysis showed that information about central contact person was more likely to be missing from records of studies registered in 2017 (adjusted OR 21.93; 95% CI 4.42-172.29; P<.001). This finding was confirmed by mediation analysis (P=.02). Furthermore, 14% of the programs were registered retrospectively. We also showed that only 33 of 77 (42.9%) expanded access studies performed in the United States and published from 2014 through 2019 were registered with CT.gov. However, multivariate logistic regression analysis showed no significant association between any of the variables related to the studies and the odds of study nonregistration (P>.01). Conclusions: Currently, CT.gov is a quite fragmentary source of data on expanded access programs. This problem is important because CT.gov is the only publicly available primary source of information about specific programs. We suggest the actions that should be taken by different stakeholders to fully exploit this register as a source of information about expanded access. UR - https://www.jmir.org/2021/10/e26890 UR - http://dx.doi.org/10.2196/26890 UR - http://www.ncbi.nlm.nih.gov/pubmed/34709189 ID - info:doi/10.2196/26890 ER - TY - JOUR AU - Mansell, Holly AU - Quinn, Declan AU - Kelly, E. Lauren AU - Szafron, Michael AU - Alcorn, Jane PY - 2021/10/18 TI - Pharmacokinetics and Perceptions of Children and Young Adults Using Cannabis for Attention-Deficit/Hyperactivity Disorder and Oppositional Defiant Disorder: Protocol for a Mixed Methods Proof-of-Concept Study JO - JMIR Res Protoc SP - e31281 VL - 10 IS - 10 KW - attention-deficit/hyperactivity disorder KW - ADHD KW - oppositional defiant disorder KW - cannabis KW - cannabidiol KW - young adults KW - youths KW - pharmacokinetics KW - marijuana N2 - Background: Despite the lack of evidence on the use of cannabis for the treatment of attention-deficit/hyperactivity disorder (ADHD), the growing perception that cannabis is safe has led more patients and caregivers to self-medicate. Some psychiatrists now authorize medicinal cannabis for patients with ADHD with features of oppositional defiant disorder (ODD) to curtail the unregulated (ie, self-medicated) use of recreational cannabis or to offer a therapeutic option to those who continue to experience symptoms after exhausting all other treatment options. Objective: This protocol aims to explore the perceived effectiveness and pharmacokinetics of cannabis in youth and young adults, who are currently taking it as part of their treatment plan for ADHD with features of ODD, under the supervision of a psychiatrist. Methods: Patients between the ages of 12 and 25 years with a diagnosis of ADHD and features of ODD, who are currently taking cannabis herbal extract (at a ?9-tetrahydrocannabinol [THC]:cannabidiol [CBD] ratio of 1:20) as a treatment adjunct to stimulant pharmacotherapy will be recruited. A sample size of 10-20 individuals is estimated. The study interview will consist of (1) validated symptom rating scales (Swanson, Nolan, and Pelham-IV Questionnaire [SNAP-IV], 90-item; Patient Health Questionnaire, 9-item [PHQ-9]; and Screen for Child Anxiety Related Emotional Disorders [SCARED] tool to measure symptoms of ADHD and ODD, depression, and anxiety, respectively); (2) a semistructured interview to probe the experiences of using cannabis; and (3) a cannabis side effects survey. A cannabis product sample as well as 2 blood samples (a trough level and 2-hour postdose level) will be collected to measure plasma concentrations of cannabinoids and relevant metabolites (THC, CBD, 11-hydroxy-THC, 7-hydroxy-CBD, cannabichromene, and 11-nor-9-carboxy-THB) using liquid chromatography?tandem mass spectrometry (LC?MS/MS). Self-report rating scales (SNAP-IV, SCARED, and PHQ-9) will be scored in accordance with standard protocols and compared to retrospective scores obtained from the participant?s chart. Demographic variables (age, weight, and race), symptom scores, and blood levels (peaks and troughs) of THC, CBD, cannabichromene (CBC), and metabolites will be summarized using descriptive statistics. Relationships between plasma concentrations and symptom scores will be determined using analysis of variance, and multiple regression analysis will be performed to determine associations between plasma concentrations and demographic variables (age, weight, and ethnicity). The qualitative data will be audio-recorded and transcribed and organized into themes. Results: The protocol was approved by the Biomedical Research Ethics Board at the University of Saskatchewan (protocol #1726), and recruitment began in May 2021. Conclusions: This proof-of-concept study will explore the potential treatment effectiveness of medical cannabis in participants with ADHD and ODD through a mixed methods approach to inform future research in this area. International Registered Report Identifier (IRRID): DERR1-10.2196/31281 UR - https://www.researchprotocols.org/2021/10/e31281 UR - http://dx.doi.org/10.2196/31281 UR - http://www.ncbi.nlm.nih.gov/pubmed/34661540 ID - info:doi/10.2196/31281 ER - TY - JOUR AU - Philipp-Muller, Emile Aaron AU - Reshetukha, Taras AU - Vazquez, Gustavo AU - Milev, Roumen AU - Armstrong, Dawn AU - Jagayat, Jasleen AU - Alavi, Nazanin PY - 2021/7/20 TI - Combining Ketamine and Internet-Based Cognitive Behavioral Therapy for the Treatment of Posttraumatic Stress Disorder: Protocol for a Randomized Controlled Trial JO - JMIR Res Protoc SP - e30334 VL - 10 IS - 7 KW - mental health KW - PTSD KW - psychotherapy KW - cognitive behavioral therapy KW - online KW - internet KW - electronic KW - virtual KW - mental health care KW - ketamine N2 - Background: Over one third of patients with posttraumatic stress disorder (PTSD) do not respond to current interventions. Ketamine presents a potential treatment option; however, its effects are temporary. Administering ketamine alongside psychotherapy is one potential means of prolonging its effects; however, only a few studies have investigated this treatment method to date, and none have tested ketamine with internet-based or electronically delivered cognitive behavioral therapy (e-CBT). Objective: This open-label randomized controlled trial aims to assess the efficacy of a combined treatment method of subanesthetic intravenous ketamine and e-CBT for treating patients with PTSD. Methods: In total, 20 patients with refractory PTSD recruited from a community clinic will be randomly assigned to either an experimental group (n=10), receiving a combination of ketamine and therapist-administered e-CBT over 14 weeks, or a waitlist control group (n=10), receiving the experimental treatment after 14 weeks. Both groups will be assessed for the symptoms of PTSD and comorbid disorders before treatment, at two midway points, and at the end of the experiment. Results: PTSD symptoms of participants in the experimental group are expected to improve significantly more than those of participants in the waitlist control group (P=.05) with a large effect size (?2=0.14). Conclusions: This is the first study to assess the relationship between e-CBT and ketamine and their combined ability to treat refractory PTSD. If successful, this study will open web-based, asynchronous therapeutic options for patients with PTSD and will provide new insights into the functional role of glutamate in trauma-related disorders as well as in learning, memory, and fear extinction. Trial Registration: ClinicalTrials.gov NCT04771767; https://clinicaltrials.gov/ct2/show/NCT04771767. International Registered Report Identifier (IRRID): PRR1-10.2196/30334 UR - https://www.researchprotocols.org/2021/7/e30334 UR - http://dx.doi.org/10.2196/30334 UR - http://www.ncbi.nlm.nih.gov/pubmed/34092549 ID - info:doi/10.2196/30334 ER - TY - JOUR AU - Grifell, Marc AU - Mir Fuster, Guillem AU - Ventura Vilamala, Mireia AU - Galindo Guarín, Liliana AU - Carbón Mallol, Xoán AU - Hart, L. Carl AU - Pérez Sola, Víctor AU - Colom Victoriano, Francesc PY - 2021/7/2 TI - Self-reported Subjective Effects of Analytically Confirmed New Psychoactive Substances Consumed by e-Psychonauts: Protocol for a Longitudinal Study Using a New Internet-Based Methodology JO - JMIR Res Protoc SP - e24433 VL - 10 IS - 7 KW - psychotropic KW - psychoactive KW - psychonautic KW - longitudinal KW - observational KW - pharmacology KW - psychopharmacology KW - subjective effects KW - sentinel KW - mental health KW - public health KW - internet KW - eHealth KW - cathinones KW - drugs of abuse KW - psychedelics KW - mobile phone KW - smart phone KW - online recruitment KW - online forums N2 - Background: During the last few years, the continuous emergence of new psychoactive substances (NPS) has become an important public health challenge. The use of NPS has been rising in two different ways: buying and consuming NPS knowingly and the presence of NPS in traditional drugs as adulterants. The rise of NPS use is increasing the number of different substances in the market to an extent impossible to study with current scientific methodologies. This has caused a remarkable absence of necessary information about newer drug effects on people who use drugs, mental health professionals, and policy makers. Current scientific methodologies have failed to provide enough data in the timeframe when critical decisions must be made, being not only too slow but also too square. Last but not least, they dramatically lack the high resolution of phenomenological details. Objective: This study aims to characterize a population of e-psychonauts and the subjective effects of the NPS they used during the study period using a new, internet-based, fast, and inexpensive methodology. This will allow bridging an evidence gap between online surveys, which do not provide substance confirmation, and clinical trials, which are too slow and expensive to keep up with the new substances appearing every week. Methods: To cover this purpose, we designed a highly personalized, observational longitudinal study methodology. Participants will be recruited from online communities of people who use NPS, and they will be followed online by means of a continuous objective and qualitative evaluation lasting for at least 1 year. In addition, participants will send samples of the substances they intend to use during that period, so they can be analyzed and matched with the effects they report on the questionnaires. Results: The research protocol was approved by the Institutional Review Board of the Hospital del Mar Research Institute on December 11, 2018. Data collection started in August 2019 and was still ongoing when the protocol was submitted (September 2020). The first data collection period of the study ended in October 2020. Data analysis began in November 2020, and it is still ongoing. The authors expect to submit the first results for publication by the end of 2021. A preliminary analysis was conducted when the manuscript was submitted and was reviewed after it was accepted in February 2021. Conclusions: It is possible to conduct an institutional review board?approved study using this new methodology and collect the expected data. However, the meaning and usefulness of these data are still unknown. International Registered Report Identifier (IRRID): DERR1-10.2196/24433 UR - https://www.researchprotocols.org/2021/7/e24433 UR - http://dx.doi.org/10.2196/24433 UR - http://www.ncbi.nlm.nih.gov/pubmed/34255715 ID - info:doi/10.2196/24433 ER - TY - JOUR AU - Dabner, Lucy AU - Pieles, E. Guido AU - Steward, G. Colin AU - Hamilton-Shield, P. Julian AU - Ness, R. Andrew AU - Rogers, A. Chris AU - Bucciarelli-Ducci, Chiara AU - Greenwood, Rosemary AU - Ellis, Lucy AU - Sheehan, Karen AU - Reeves, C. Barnaby PY - 2021/5/31 TI - Treatment of Barth Syndrome by Cardiolipin Manipulation (CARDIOMAN) With Bezafibrate: Protocol for a Randomized Placebo-Controlled Pilot Trial Conducted in the Nationally Commissioned Barth Syndrome Service JO - JMIR Res Protoc SP - e22533 VL - 10 IS - 5 KW - randomized controlled trial KW - Barth syndrome KW - cardiomyopathies KW - inherited cardiomyopathy KW - bezafibrate KW - placebo controlled KW - rare disease KW - resveratrol KW - cardiomyopathy KW - metabolism KW - lipid KW - genetic diseases KW - x-linked KW - genes KW - mitochondrial KW - controlled clinical trial KW - placebos KW - mitochondrial diseases KW - metabolic diseases KW - lipid metabolism KW - lipid metabolism disorders KW - cross-over studies N2 - Background: Barth syndrome is a rare, life-threatening, X-linked recessive genetic disease that predominantly affects young males and is caused by abnormal mitochondrial lipid metabolism. Currently, there is no definitive treatment for Barth syndrome other than interventions to ameliorate acute symptoms, such as heart failure, cardiac arrhythmias, neutropenia, and severe muscle fatigue. Previous mechanistic studies have identified the lipid-lowering drug bezafibrate as a promising potential treatment; however, to date, no human trials have been performed in this population. Objective: The aim of this study is to determine whether bezafibrate (and resveratrol in vitro) will increase mitochondrial biogenesis and potentially modify the cellular ratio of monolysocardiolipin (MLCL) to tetralinoleoyl-cardiolipin (L4-CL), ameliorating the disease phenotype in those living with the disease. Methods: The CARDIOMAN (Cardiolipin Manipulation) study is a UK single-center, double-blinded, randomized, placebo-controlled crossover study investigating the efficacy of bezafibrate in participants with Barth syndrome. Treatment was administered in two 15-week phases with a minimum washout period of 1 month between the phases where no treatment was administered. The primary outcome is peak oxygen consumption (VO2 peak). Secondary outcomes include MLCL/L4-CL ratio and CL profile in blood cells, amino acid expression, phosphocreatine to adenosine triphosphate ratio in cardiac muscle and skeletal muscle oxidative function on phosphorus-31 magnetic resonance spectroscopy, quality of life using the Pediatric Quality of Life Inventory questionnaire, absolute neutrophil count, cardiac function and rhythm profiles at rest and during exercise, and mitochondrial organization and function assessments. Outcomes were assessed at baseline and during the final week of each treatment phase. Results: A total of 12 patients were scheduled to participate across three consecutive research clinics between March and April 2019. In total, 11 participants were recruited, and the follow-up was completed in January 2020. Data analysis is ongoing, with publication expected in 2021. Conclusions: This trial was approved by the United Kingdom National Research Ethics Service Committee and the Medicines and Healthcare products Regulatory Agency. The feasibility of the CARDIOMAN study will help to inform the future conduct of randomized controlled trials in rare disease populations as well as testing the efficacy of bezafibrate as a potential treatment for the disease and advancing the mechanistic understanding of Barth syndrome. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 58006579; https://www.isrctn.com/ISRCTN58006579 International Registered Report Identifier (IRRID): DERR1-10.2196/22533 UR - https://www.researchprotocols.org/2021/5/e22533 UR - http://dx.doi.org/10.2196/22533 UR - http://www.ncbi.nlm.nih.gov/pubmed/34057417 ID - info:doi/10.2196/22533 ER - TY - JOUR AU - Niburski, Kacper AU - Niburski, Oskar PY - 2020/11/20 TI - Impact of Trump's Promotion of Unproven COVID-19 Treatments and Subsequent Internet Trends: Observational Study JO - J Med Internet Res SP - e20044 VL - 22 IS - 11 KW - COVID-19 KW - behavioral economics KW - public health KW - behavior KW - economics KW - media KW - influence KW - infodemic KW - infodemiology KW - infoveillance KW - Twitter KW - analysis KW - trend N2 - Background: Individuals with large followings can influence public opinions and behaviors, especially during a pandemic. In the early days of the pandemic, US president Donald J Trump has endorsed the use of unproven therapies. Subsequently, a death attributed to the wrongful ingestion of a chloroquine-containing compound occurred. Objective: We investigated Donald J Trump?s speeches and Twitter posts, as well as Google searches and Amazon purchases, and television airtime for mentions of hydroxychloroquine, chloroquine, azithromycin, and remdesivir. Methods: Twitter sourcing was catalogued with Factba.se, and analytics data, both past and present, were analyzed with Tweet Binder to assess average analytics data on key metrics. Donald J Trump?s time spent discussing unverified treatments on the United States? 5 largest TV stations was catalogued with the Global Database of Events, Language, and Tone, and his speech transcripts were obtained from White House briefings. Google searches and shopping trends were analyzed with Google Trends. Amazon purchases were assessed using Helium 10 software. Results: From March 1 to April 30, 2020, Donald J Trump made 11 tweets about unproven therapies and mentioned these therapies 65 times in White House briefings, especially touting hydroxychloroquine and chloroquine. These tweets had an impression reach of 300% above Donald J Trump?s average. Following these tweets, at least 2% of airtime on conservative networks for treatment modalities like azithromycin and continuous mentions of such treatments were observed on stations like Fox News. Google searches and purchases increased following his first press conference on March 19, 2020, and increased again following his tweets on March 21, 2020. The same is true for medications on Amazon, with purchases for medicine substitutes, such as hydroxychloroquine, increasing by 200%. Conclusions: Individuals in positions of power can sway public purchasing, resulting in undesired effects when the individuals? claims are unverified. Public health officials must work to dissuade the use of unproven treatments for COVID-19. UR - http://www.jmir.org/2020/11/e20044/ UR - http://dx.doi.org/10.2196/20044 UR - http://www.ncbi.nlm.nih.gov/pubmed/33151895 ID - info:doi/10.2196/20044 ER - TY - JOUR AU - Khan, Younus Junaed AU - Khondaker, Islam Md Tawkat AU - Hoque, Tazim Iram AU - Al-Absi, H. Hamada R. AU - Rahman, Saifur Mohammad AU - Guler, Reto AU - Alam, Tanvir AU - Rahman, Sohel M. PY - 2020/11/10 TI - Toward Preparing a Knowledge Base to Explore Potential Drugs and Biomedical Entities Related to COVID-19: Automated Computational Approach JO - JMIR Med Inform SP - e21648 VL - 8 IS - 11 KW - COVID-19 KW - 2019-nCoV KW - coronavirus KW - SARS-CoV-2 KW - SARS KW - remdesivir KW - statin KW - statins KW - dexamethasone KW - ivermectin KW - hydroxychloroquine N2 - Background: Novel coronavirus disease 2019 (COVID-19) is taking a huge toll on public health. Along with the non-therapeutic preventive measurements, scientific efforts are currently focused, mainly, on the development of vaccines and pharmacological treatment with existing drugs. Summarizing evidences from scientific literatures on the discovery of treatment plan of COVID-19 under a platform would help the scientific community to explore the opportunities in a systematic fashion. Objective: The aim of this study is to explore the potential drugs and biomedical entities related to coronavirus related diseases, including COVID-19, that are mentioned on scientific literature through an automated computational approach. Methods: We mined the information from publicly available scientific literature and related public resources. Six topic-specific dictionaries, including human genes, human miRNAs, diseases, Protein Databank, drugs, and drug side effects, were integrated to mine all scientific evidence related to COVID-19. We employed an automated literature mining and labeling system through a novel approach to measure the effectiveness of drugs against diseases based on natural language processing, sentiment analysis, and deep learning. We also applied the concept of cosine similarity to confidently infer the associations between diseases and genes. Results: Based on the literature mining, we identified 1805 diseases, 2454 drugs, 1910 genes that are related to coronavirus related diseases including COVID-19. Integrating the extracted information, we developed the first knowledgebase platform dedicated to COVID-19, which highlights potential list of drugs and related biomedical entities. For COVID-19, we highlighted multiple case studies on existing drugs along with a confidence score for their applicability in the treatment plan. Based on our computational method, we found Remdesivir, Statins, Dexamethasone, and Ivermectin could be considered as potential effective drugs to improve clinical status and lower mortality in patients hospitalized with COVID-19. We also found that Hydroxychloroquine could not be considered as an effective drug for COVID-19. The resulting knowledgebase is made available as an open source tool, named COVID-19Base. Conclusions: Proper investigation of the mined biomedical entities along with the identified interactions among those would help the research community to discover possible ways for the therapeutic treatment of COVID-19. UR - http://medinform.jmir.org/2020/11/e21648/ UR - http://dx.doi.org/10.2196/21648 UR - http://www.ncbi.nlm.nih.gov/pubmed/33055059 ID - info:doi/10.2196/21648 ER - TY - JOUR AU - Rogosnitzky, Moshe AU - Berkowitz, Esther AU - Jadad, R. Alejandro PY - 2020/9/30 TI - No Time to Waste: Real-World Repurposing of Generic Drugs as a Multifaceted Strategy Against COVID-19 JO - JMIRx Med SP - e19583 VL - 1 IS - 1 KW - COVID-19 KW - drug repurposing KW - fibrates KW - histamine type-2 receptor antagonists KW - cimetidine KW - famotidine KW - fenofibrate KW - bezafibrate KW - dipyridamole KW - sildenafil UR - https://med.jmirx.org/2020/1/e19583/ UR - http://dx.doi.org/10.2196/19583 UR - http://www.ncbi.nlm.nih.gov/pubmed/33724265 ID - info:doi/10.2196/19583 ER - TY - JOUR AU - Michelson, Matthew AU - Chow, Tiffany AU - Martin, A. Neil AU - Ross, Mike AU - Tee Qiao Ying, Amelia AU - Minton, Steven PY - 2020/8/17 TI - Artificial Intelligence for Rapid Meta-Analysis: Case Study on Ocular Toxicity of Hydroxychloroquine JO - J Med Internet Res SP - e20007 VL - 22 IS - 8 KW - meta-analysis KW - rapid meta-analysis KW - artificial intelligence KW - drug KW - analysis KW - hydroxychloroquine KW - toxic KW - COVID-19 KW - treatment KW - side effect KW - ocular KW - eye N2 - Background: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance. Objective: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example. Methods: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and vision compromise a side effect of hydroxychloroquine therapy? At the time of designing this study, hydroxychloroquine was a leading candidate in the treatment of coronavirus disease (COVID-19). We then leveraged AI to pull and screen articles, automatically extract their results, review the studies, and analyze the data with standard statistical methods. Results: By combining AI with human analysis in our RMA, we generated a meaningful, clinical result in less than 30 minutes. The RMA identified 11 studies considering ocular toxicity as a side effect of hydroxychloroquine and estimated the incidence to be 3.4% (95% CI 1.11%-9.96%). The heterogeneity across individual study findings was high, which should be taken into account in interpretation of the result. Conclusions: We demonstrate that a novel approach to meta-analysis using AI can generate meaningful clinical insights in a much shorter time period than traditional meta-analysis. UR - http://www.jmir.org/2020/8/e20007/ UR - http://dx.doi.org/10.2196/20007 UR - http://www.ncbi.nlm.nih.gov/pubmed/32804086 ID - info:doi/10.2196/20007 ER - TY - JOUR AU - Li, Xin AU - Rousseau, F. Justin AU - Ding, Ying AU - Song, Min AU - Lu, Wei PY - 2020/6/16 TI - Understanding Drug Repurposing From the Perspective of Biomedical Entities and Their Evolution: Bibliographic Research Using Aspirin JO - JMIR Med Inform SP - e16739 VL - 8 IS - 6 KW - drug repurposing KW - biomedical entities KW - entitymetrics KW - bibliometrics KW - aspirin KW - acetylsalicylic acid N2 - Background: Drug development is still a costly and time-consuming process with a low rate of success. Drug repurposing (DR) has attracted significant attention because of its significant advantages over traditional approaches in terms of development time, cost, and safety. Entitymetrics, defined as bibliometric indicators based on biomedical entities (eg, diseases, drugs, and genes) studied in the biomedical literature, make it possible for researchers to measure knowledge evolution and the transfer of drug research. Objective: The purpose of this study was to understand DR from the perspective of biomedical entities (diseases, drugs, and genes) and their evolution. Methods: In the work reported in this paper, we extended the bibliometric indicators of biomedical entities mentioned in PubMed to detect potential patterns of biomedical entities in various phases of drug research and investigate the factors driving DR. We used aspirin (acetylsalicylic acid) as the subject of the study since it can be repurposed for many applications. We propose 4 easy, transparent measures based on entitymetrics to investigate DR for aspirin: Popularity Index (P1), Promising Index (P2), Prestige Index (P3), and Collaboration Index (CI). Results: We found that the maxima of P1, P3, and CI are closely associated with the different repurposing phases of aspirin. These metrics enabled us to observe the way in which biomedical entities interacted with the drug during the various phases of DR and to analyze the potential driving factors for DR at the entity level. P1 and CI were indicative of the dynamic trends of a specific biomedical entity over a long time period, while P2 was more sensitive to immediate changes. P3 reflected the early signs of the practical value of biomedical entities and could be valuable for tracking the research frontiers of a drug. Conclusions: In-depth studies of side effects and mechanisms, fierce market competition, and advanced life science technologies are driving factors for DR. This study showcases the way in which researchers can examine the evolution of DR using entitymetrics, an approach that can be valuable for enhancing decision making in the field of drug discovery and development. UR - https://medinform.jmir.org/2020/6/e16739 UR - http://dx.doi.org/10.2196/16739 UR - http://www.ncbi.nlm.nih.gov/pubmed/32543442 ID - info:doi/10.2196/16739 ER - TY - JOUR AU - Rogosnitzky, Moshe AU - Berkowitz, Esther AU - Jadad, R. Alejandro PY - 2020/5/13 TI - Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point JO - JMIR Public Health Surveill SP - e19199 VL - 6 IS - 2 KW - COVID-19 KW - drug costs KW - drug repositioning KW - drugs, generic KW - off-label use KW - public health KW - severe acute respiratory syndrome coronavirus 2 KW - pandemic KW - crisis UR - http://publichealth.jmir.org/2020/2/e19199/ UR - http://dx.doi.org/10.2196/19199 UR - http://www.ncbi.nlm.nih.gov/pubmed/32374264 ID - info:doi/10.2196/19199 ER - TY - JOUR AU - Zhao, Mengnan AU - Yang, C. Christopher PY - 2018/10/11 TI - Drug Repositioning to Accelerate Drug Development Using Social Media Data: Computational Study on Parkinson Disease JO - J Med Internet Res SP - e271 VL - 20 IS - 10 KW - drug repositioning KW - Parkinson disease KW - heterogeneous network KW - social media N2 - Background: Due to the high cost and low success rate in new drug development, systematic drug repositioning methods are exploited to find new indications for existing drugs. Objective: We sought to propose a new computational drug repositioning method to identify repositioning drugs for Parkinson disease (PD). Methods: We developed a novel heterogeneous network mining repositioning method that constructed a 3-layer network of disease, drug, and adverse drug reaction and involved user-generated data from online health communities to identify potential candidate drugs for PD. Results: We identified 44 non-Parkinson drugs by using the proposed approach, with data collected from both pharmaceutical databases and online health communities. Based on the further literature analysis, we found literature evidence for 28 drugs. Conclusions: In summary, the proposed heterogeneous network mining repositioning approach is promising for identifying repositioning candidates for PD. It shows that adverse drug reactions are potential intermediaries to reveal relationships between disease and drug. UR - http://www.jmir.org/2018/10/e271/ UR - http://dx.doi.org/10.2196/jmir.9646 UR - http://www.ncbi.nlm.nih.gov/pubmed/30309833 ID - info:doi/10.2196/jmir.9646 ER - TY - JOUR AU - Rastegar-Mojarad, Majid AU - Liu, Hongfang AU - Nambisan, Priya PY - 2016/06/16 TI - Using Social Media Data to Identify Potential Candidates for Drug Repurposing: A Feasibility Study JO - JMIR Res Protoc SP - e121 VL - 5 IS - 2 KW - social media KW - drug repurposing KW - natural language processing KW - patient comments N2 - Background: Drug repurposing (defined as discovering new indications for existing drugs) could play a significant role in drug development, especially considering the declining success rates of developing novel drugs. Typically, new indications for existing medications are identified by accident. However, new technologies and a large number of available resources enable the development of systematic approaches to identify and validate drug-repurposing candidates. Patients today report their experiences with medications on social media and reveal side effects as well as beneficial effects of those medications. Objective: Our aim was to assess the feasibility of using patient reviews from social media to identify potential candidates for drug repurposing. Methods: We retrieved patient reviews of 180 medications from an online forum, WebMD. Using dictionary-based and machine learning approaches, we identified disease names in the reviews. Several publicly available resources were used to exclude comments containing known indications and adverse drug effects. After manually reviewing some of the remaining comments, we implemented a rule-based system to identify beneficial effects. Results: The dictionary-based system and machine learning system identified 2178 and 6171 disease names respectively in 64,616 patient comments. We provided a list of 10 common patterns that patients used to report any beneficial effects or uses of medication. After manually reviewing the comments tagged by our rule-based system, we identified five potential drug repurposing candidates. Conclusions: To our knowledge, this is the first study to consider using social media data to identify drug-repurposing candidates. We found that even a rule-based system, with a limited number of rules, could identify beneficial effect mentions in patient comments. Our preliminary study shows that social media has the potential to be used in drug repurposing. UR - http://www.researchprotocols.org/2016/2/e121/ UR - http://dx.doi.org/10.2196/resprot.5621 UR - http://www.ncbi.nlm.nih.gov/pubmed/27311964 ID - info:doi/10.2196/resprot.5621 ER - TY - JOUR AU - Wang, Kejian AU - Wan, Mei AU - Wang, Rui-Sheng AU - Weng, Zuquan PY - 2016/04/01 TI - Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events JO - J Med Internet Res SP - e76 VL - 18 IS - 4 KW - Web-based drug repositioning KW - FDA Adverse Event Reporting System KW - FAERS KW - openFDA KW - big data KW - antihypertensive drugs KW - hypotension N2 - Background: Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. Objective: We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. Methods: We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Results: Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. Conclusions: We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning. UR - http://www.jmir.org/2016/4/e76/ UR - http://dx.doi.org/10.2196/jmir.4541 UR - http://www.ncbi.nlm.nih.gov/pubmed/27036325 ID - info:doi/10.2196/jmir.4541 ER -